Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Gland and Hormone Related Diseases

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Mouth and Tooth Diseases

Eye Diseases

Rare Diseases

Breast Neoplasms

Thyroid Neoplasms

Thyroid Diseases

Neoplasm Metastasis

Urologic Neoplasms

Genital Neoplasms, Female

Lip Neoplasms

Eye Neoplasms

Genital Neoplasms, Male

Breast Diseases

Skin Diseases

Urogenital Neoplasms

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Diseases, Male

Male Urogenital Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Endocrine System Diseases

Mouth Neoplasms

Mouth Diseases

Stomatognathic Diseases

Urologic Diseases

Oral Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Pembrolizumab

Doxycycline

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Anti-Bacterial Agents

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Participants receive Pembrolizumab by vein over about 30 minutes on Day 0 and then every 3 weeks for up to 12 months.

Clostridium novyi-NT injected into the tumor on Day 8.

Starting on Day 15, participant takes Doxycycline by mouth 2 times a day for the rest of participant's life to lower the risk of further growth of Clostridium novyi-NT

200 mg by intravenous infusion starting on Day 0, and continuing every 3 weeks for up to 12 months.

Participants given a single dose of Clostridium Novyi-NT by intratumoral injection on Day 8.

Clostridium Novyi-NT administered starting with Cohort 1 at a dose of 3 x 10\^4 spores followed by dose escalation.

Clostridium Novyi-NT

Starting on Day 15, participant takes Doxycycline by mouth 2 times a day for the rest of participant's life to lower the risk of further growth of Clostridium novyi-NT

Sarina Piha-Paul, MD, PHD

Sarina Piha-Paul, MD

Some tumors are difficult to treat with chemotherapy or radiation. One of the reasons is that areas of the tumor do not have many blood vessels, which makes it difficult for drugs to reach those areas. One way that researchers have recently tried to overcome this problem is by injecting special kinds of bacteria into the tumors. These bacteria have been genetically changed to remove the chemicals that are poisonous to humans, but are still able to cause tumor cells to break down and die. The idea is that these bacteria may be able to assist chemotherapy drugs in fighting cancer.

The goal of this clinical research study is to find the highest tolerable dose of one of these bacterial therapies (Clostridium novyi-NT spores) that can be given in combination with pembrolizumab to patients with advanced solid tumors. The safety of this drug will also be studied, as well as whether it can help to control the disease.

This is an investigational study. Clostridium novyi-NT is not FDA approved or commercially available. It is currently being used for research purposes only. Pembrolizumab is FDA approved for the treatment of melanoma and different types of head and neck and non-small cell lung cancers. It is investigational to use these drugs in combination with each other in various types of advanced cancers.

The study doctor can describe how the study drugs are designed to work.

Up to 18 participants will be enrolled in this study. All will take part at MD Anderson.

Study Drug Dose Levels:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of Clostridium novyi-NT based on when you join this study. Up to 4 dose levels will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level of Clostridium novyi-NT. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of Clostridium novyi-NT is found, or all 4 dose levels are filled.

During the study, the supporting company (BioMed Valley Discoveries, Inc.) and study doctors may increase the number of patients in a dose group based on the available study results. This will not change your participation while on study.

All participants will receive the same dose level of pembrolizumab.

Study Drug Administration:

You will receive pembrolizumab by vein over about 30 minutes on Day 0 and then every 3 weeks for up to 12 months.

Clostridium novyi-NT will be injected into the tumor on Day 8. This is the only injection into the tumor you will receive. Your doctors may use an x-ray or ultrasound to help place the needle into the tumor. You will be in the hospital for 7 days to check for side effects, or possibly longer if your study doctor thinks it is needed. You will be able to go home if you have no signs or symptoms of infection. If the study doctor thinks it is needed (for example, based on your tests or any infection symptoms), you may need to return to the hospital at a later time.

Starting on Day 15, you will take an antibiotic (doxycycline) by mouth 2 times a day for the rest of your life to lower the risk of further growth of Clostridium novyi-NT. This is because the study drug is a changed form of bacteria. If you miss a dose or forget to take doxycycline, take it as soon as you can. If it is almost time for your next dose, wait until then to take it and you should skip the missed dose. Do not take an extra dose to make up for a missed dose.

If the doctor thinks it is needed, you will also take additional antibiotics, piperacillin/tazobactam and metronidazole. The antibiotic that is given and the length of time you need to take it will depend on your reaction to the study drug. You should still continue to take doxycycline. Your doctor will discuss this with you. You may receive piperacillin/tazobactam by vein over about 30 minutes and metronidazole by vein over about 30-60 minutes as often as your doctor tells you to, until your doctor thinks it is acceptable for you to change to taking the antibiotics by mouth. In some cases, if you need to receive antibiotics by vein for more than a week or two, your doctor may ask you to have a central venous catheter placed. A central venous catheter is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form.

You may also be given other standard drugs to help decrease the risk of side effects. You may ask the study staff for information about how the drugs are given and their risks.

Length of Study Participation:

You may receive 1 dose of Clostridium novyi-NT and receive pembrolizumab every 3 weeks for up to 12 months. You will then have 12 months of follow-up after you receive the last dose of pembrolizumab. You will be taken off study early if the disease gets worse, if you have intolerable side effects, or if you are unable to follow study directions.

Your participation on the study will be over after the Month 12 post-dosing follow-up visit.

If you leave the study early, you or your family will be called every 3 months for up to 12 months to see how you are doing. These calls should last less than 30 minutes each time.

Study Visits and Calls:

For your safety, you must stay within 45 minutes driving distance from an emergency room and also have a caregiver available for at least 28 days after you receive your dose of Clostridium novyi-NT spores.

If an abscess (a swollen area of infection that contains pus) forms in the tumor and it needs to be drained, the study doctor may decide to collect some of the drainage for research tests to study the infection and test your immune system response.

Tumor biopsy samples (described below) may be collected at different times than listed, or not at all, depending on the inflammation around the tumor, the amount of tissue available, or how easily it can be collected.

On Days 0 and 1:

* You will have a physical exam.
* You will have an EKG to check your heart function.
* You will have a biopsy sample collected from the target tumor before you receive pembrolizumab. The tumor sample will be used for biomarker testing, including genetic biomarkers and to check your body's inflammatory and immune responses to the study drug. Biomarkers are found in the blood/tissue and may be related to your reaction to the study drug. The type of biopsy you have will depend on the location of the disease. The study staff will describe this procedure in more detail, including its risks.
* If you can become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test.

On Day 8:

* You will have a physical exam.
* Blood (about 4 ½ tablespoons) will be drawn for routine tests, to find out how long the Clostridium novyi-NT spores and bacteria stay in your body, and to measure your risk for bacteremia at 1 hour and 12 hours after the study drug dose.

On Days 9-15 daily:

* You will have a physical exam.
* Blood (about 1½ teaspoons) will be drawn for routine tests.
* You will have either a CT scan or MRI to check the status of the disease (Day 15 only).
* If you have any skin lesions, photographs will be taken of these lesions.

After you leave the hospital and during the first 28 days after you receive Clostridium novyi-NT spores, the study staff will call you 1 time each day on the days you do not have study visits. You will be asked how you are doing. The calls should last less than 30 minutes each time.

On Days 18 and 25, you will have a physical exam.

On Days 21 and 28:

* You will have a physical exam.
* Blood (about 1½ teaspoons) will be drawn for routine tests.

On Days 35:

* You will have a physical exam.
* Blood (about 4 ½ tablespoons) will be drawn for routine tests, to check your body's inflammatory and immune system response to the study drug, to find out how long the Clostridium novyi-NT spores and bacteria stay in your body, and to measure your risk for bacteremia.

At Weeks 6, 9, 15, 24, 39, 45, and 48, you will have a physical exam.

Every 3 weeks beginning with Week 6, blood (about 1 tablespoon) will be drawn for routine testing.

Every 6 weeks beginning with Week 6:

* You will have either a CT scan or MRI to check the status of the disease.
* If you have any skin lesions, photographs will be taken of these lesions.

At Week 9, blood (about 1 teaspoon) will also be drawn for HLA testing.

At Week 12, you will have a tumor tissue biopsy sample collected of the injected tumor and a non-injected tumor for biomarker testing and to help learn how your body is responding to the study drug.

At Weeks 9, 24, 33 and 48, blood (about 4 ½ tablespoons) will be drawn for routine tests, to check your body's inflammatory and immune system response to the study drug, to find out how long the Clostridium novyi-NT spores and bacteria stay in your body, and to measure your risk for bacteremia.

The tests and procedures may be repeated anytime the doctor thinks it is needed.

End of Study Visit:

After you stop receiving the study drug(s):

* Blood (about 3½ tablespoons) will be drawn for routine tests, to check your body's inflammatory and immune system response to the study drug, to find out how long the Clostridium novyi-NT spores and bacteria stay in your body, and to measure your risk for bacteremia.
* You will have either a CT scan or MRI to check the status of the disease.
* If you have any skin lesions, photographs will be taken of these lesions.

Follow Up Visit:

About 30 days after your last dose of pembrolizumab:

* You will have a physical exam.
* Blood (about 1 tablespoon) and urine will be collected for routine tests.
* You will have either a CT scan or MRI to check the status of the disease. It will be repeated every 3 months for up to 12 months.
* If you have any skin lesions, photographs will be taken of these lesions.

After the last follow-up visit, you or a family member will be called every 3 months for an additional year and asked about how you are doing. Each call should last about 15 minutes.

Pembrolizumab With Intratumoral Injection of Clostridium Novyi-NT

A Phase Ib Investigation of Pembrolizumab in Combination With Intratumoral Injection of Clostridium Novyi-NT in Patients With Treatment-Refractory Solid Tumors

MTD defined as the highest dose studied in which the incidence of DLT was less than 33%.

BioMed Valley Discoveries, Inc

Merck Sharp & Dohme LLC

M.D. Anderson Cancer Center

Urinary Bladder Neoplasms

Other Dietary Supplements

Amino Acids

Omega 3 Fatty Acid

Arginine

Participants take 1 ounce (30mls) of Arginine recovery supplement (ARS) four times daily 5 days preoperatively and 14 days postoperatively.

Participants also given omega-3 fatty acids, 1 gram four times a day, 4 grams total per day. This will be started 7 days preoperatively and continued 14 days postoperatively.

Participants receive regular enhanced recovery after surgery (ERAS)/Optimized Surgical Journey (OSJ) education and follow up.

Participants take 1 ounce (30mls) of Arginine recovery supplement four times daily 5 days preoperatively and 14 days postoperatively.

Arginine recovery supplement

Participants given omega-3 fatty acids, 1 gram four times a day, 4 grams total per day. This will be started 7 days preoperatively and continued 14 days postoperatively.

Omega-3 Fatty Acids

Neema Navai, MD

The goal of this clinical research study is to learn the supplements Pro-Stat (which has l-arginine and also contains protein) and omega-3 fatty acids will be well tolerated in patients who have radical cystectomy for bladder cancer. Researchers also want to learn how these medications affect inflammation and recovery for these surgical patients.

This is an investigational study. Pro-Stat is not FDA-approved to treat any specific condition or disease. Omega-3 fatty acids are FDA-approved to treat high triglyceride levels. Their use to treat inflammation and help improve recovery after bladder cancer surgery is investigational.

The study doctor can explain how the supplements are designed to work.

Up to 46 participants will be enrolled in this study. All will take part at MD Anderson.

If you agree to take part in this study, you will be asked to perform a few tasks to learn about your strength, memory, and nutrition. These should take about 20 minutes to complete.

Study Groups:

You will be randomly assigned (as in the flip of a coin) into 1 of 2 study groups. This is done because no one knows if one study group is better, the same, or worse than the other group.

* If you are in Group 1, you will receive the Pro-Stat and omega-3 fatty acid supplements.
* If you are in Group 2, you will not receive the Pro-Stat and omega-3 fatty acid supplements.

You will be asked to write down any supplements you take in a diary that will be provided to you. You should write down any supplements you take for the week before and 2 weeks after surgery. Please bring this diary to your follow up appointment after surgery.

Supplement Administration:

If you are in Group 1, you will receive the omega-3 fatty acids in a pill bottle and the Pro-Stat in foil packets. You should take each supplement 4 times daily. Omega-3 fatty acid capsules should be swallowed whole and should not be opened, chewed, or crushed.

Packets of Pro-Stat may be mixed with other liquids or food. If vomiting occurs, do not replace the vomited dose. If you miss a dose, you may take an extra dose that same day.

You should bring all supplements you haven't taken with you to your 14 day visit after surgery.

Length of Study Participation:

Your doctor may lower the dose of the supplements if you experience any serious side effects that may be related to the supplements. If these side effects continue after the dose has been lowered, you will no longer be able to take the supplements. You may also be taken off study if you are unable to follow study directions.

Your participation on the study will be over after the follow-up visits.

Surgery:

You will have your standard-of-care surgery. You will receive a separate consent for the surgery that explains the procedure and the risks.

Study/Follow-Up Visits:

Before Surgery:

* Blood (about 8 teaspoons) will be drawn for routine tests, protein testing, biomarker testing, to check your cholesterol, liver function, your amino acid levels, and to test for inflammatory markers. Biomarkers are found in the blood and may be related to your reaction to the supplements.
* Urine will be collected for routine tests.
* Blood (about 4 teaspoons) will also be drawn and stored at MD Anderson for future testing as a part of this study.

Day 1 After Surgery:

* Blood (about 2 teaspoons) will be drawn for routine tests.
* Blood (about 4 teaspoons) will also be drawn and stored at MD Anderson for future testing as a part of this study.

Day 2 After Surgery, blood (about 2 teaspoons) will be drawn for routine tests.

Day 3 After Surgery:

* Blood (about 2 teaspoons) will be drawn for routine tests.
* Blood (about 4 teaspoons) will also be drawn and stored at MD Anderson for future testing as a part of this study.

On your Day of Discharge from the hospital:

* Blood (about 2 teaspoons) will be drawn for routine tests.
* Urine will be collected for routine tests.

Day 14 After Surgery:

* Blood (about 2 teaspoons) will be drawn for routine tests, to check your cholesterol, your liver function, and your amino acid levels.
* Urine will be collected for routine tests.
* Blood (about 4 teaspoons) will also be drawn and stored at MD Anderson for future testing as a part of this study.

You weight will be measured at all of the above visits and information will be collected from your medical record.

Day 90 After Surgery, you will have a physical exam and your weight will be recorded.

Oral Supplementation to Enhance Recovery Pilot Study

Participant compliance defined as "Yes" if a participant completes at least 16 out of the total 21 days' treatment.

Poor recovery determined by length of stay greater than 7 days.

Poor recovery determined by any postoperative infection.

Poor recovery determined by hospital readmission within 90 days after radical cystectomy.

Poor recovery determined by death within 90 days of cystectomy.

IL-6 levels drawn postoperative day 1 within 24 hours of anesthesia induction. This used to create a response curve based on the administration of immunonutrition.

National Cancer Institute (NCI)

Musculoskeletal Diseases

Carcinoma

Melanoma

Skin Neoplasms

Osteosarcoma

Bone Neoplasms

Neoplastic Processes

Bone Diseases

Pharmaceutical Solutions

Gemcitabine

Antimetabolites

Dose Escalation Cohort: Participants take Gemcitabine by mist 2 times each week for 4 weeks (28 days).

Expansion Cohort: Participants with OS lung metastases receive study drug at the maximum tolerated dose from Dose Escalation Cohort.

Participants may continue to receive the study drug for up to 12 cycles per decision of doctor.

Nebulized dose of aerosol GCB twice a week continuously (escalating treatment dose schema, starting at 0.75 mg/kg to 3.0 mg/kg). Participants receive a pre-determined volume of nebulized solution, according to the dose level and weight of the participant, with each aerosol GCB administration. One cycle is 4 weeks in duration.

Najat C. Daw-Bitar, MD

Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant.

The goal of this clinical research study is to find the highest tolerable dose of gemcitabine that can be given by inhalation (breathing it as a mist) to patients with solid tumors that have spread to the lungs from other parts of the body.

The safety and side effects of this drug will also be studied.

This is an investigational study. Gemcitabine is FDA approved and commercially available for the treatment of pancreatic and lung cancer, and other solid tumors. Its administration by inhalation is investigational. The study doctor can explain how the study drug is designed to work.

Up to 44 participants will be enrolled in this study. All will take part at MD Anderson.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of gemcitabine based on when you join this study. Up to 6 dose levels of gemcitabine will be tested. Up to 3 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects are seen. This will continue until the highest tolerable dose of gemcitabine is found.

Each study cycle is 28 days. You will take gemcitabine by mist 2 times each week for 4 weeks (28 days). Treatment will be administered at MD Anderson. A machine called a nebulizer will be used to make the gemcitabine mist. The study staff will provide you with protective materials and instructions on how to take the treatment. You will breathe the drug mist through the mouthpiece of the nebulizer. The study staff will tell you which days you will receive the study drug. If the doctor thinks it is in your best interest, you may continue to receive the study drug for up to 12 cycles.

Length of Study:

You may continue taking the study drug for up to 12 cycles. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. If you have developed a tumor outside of the lungs either before or while you are on study, and the doctor thinks it is in your best interest, you may have a local control procedure (such as radiation or surgery) that may help to control the disease while continuing to receive the study drug. You would sign a separate consent form explaining these procedures and their risks. If you and your doctor decide on a systemic cancer treatment by mouth or vein, you will no longer be able to receive treatment on this study. A systemic cancer treatment is designed to spread and treat cancer cells throughout the body.

Your participation on the study will be over after your last follow-up phone call.

Study Visits:

Within 3 days before Day 1 of every cycle:

* You will have a physical exam.
* Blood (about 4 teaspoons) will be drawn for routine tests and to check your liver function.
* You will have PFTs.
* You will have your blood oxygen level measured by pulse oximeter.
* If you can become pregnant, urine will be collected for a pregnancy test.

On Day 8 of Cycle 1:

* You will have a physical exam.
* Blood (about 4 teaspoons) will be drawn for routine tests and to check your liver function.

You will have a CT scan at the end of Cycles 2, 4, and 6, and then every 3 cycles after that. The study doctor will tell you when you will have these scans. If you have a chest X-ray, MRI, and PET scan as part of standard of care while you are on study, the study doctor may use the results to check the status of the disease.

To avoid having to come to the study clinic too often, you may have blood draws done by your personal doctor.

You may be called by the study staff and asked about how you are doing and about any side effects about 1 day after your first 2 doses of the study drug, at the end of Cycle 1, and 1 time every 3 months after that until you leave the study or the study ends. These calls should last about 15-20 minutes each time.

Other Information:

Each day that you take study drug:

* You will write down the date and the day of the study cycle in a dosing diary given to you by the study staff. You should bring the diary to all clinic visits.
* You will be given a pulse oximeter to measure your heart rate and blood oxygen level. °You should record your results in the dosing diary.
* You will use a small hand-held device to test your lung function before the dose and answer questions about side effects you may be having.

You will also be given an electronic device (such as a laptop or tablet) so that you can upload the information from the lung function tests and send it to the study doctor. You will only be able to access study specific material on this device. The study staff will show you how to use all of the provided machines. If the device is lost, stolen, or damaged, you will need to immediately report it to the study staff and you will be responsible for its replacement.

You should bring the nebulizer with you to all study visits.

You will be asked to return the nebulizer, pulse oximeter, lung function device, and electronic device when your participation on this study is over.

End of Dosing Visit:

Within 30 days of your last dose of the study drug:

* You will have a physical exam.
* Blood (about 4 teaspoons) will be drawn for routine tests.
* You will have PFTs.
* You will have your blood oxygen level measured by pulse oximeter.
* You will have a CT scan.

Study of Aerosol Gemcitabine in Patients With Solid Tumors and Pulmonary Metastases

Phase I Study of Aerosol Gemcitabine in Patients With Solid Tumors and Pulmonary Metastases

MTD is defined as highest dose level with six patients with at most 1 dose limiting toxicity (DLT) occurring during cycle 1. Dose levels will continue to be increased until 1 participant experiences DLT. If only 1 of 3 participants experiences DLT, 3 additional patients will be entered.

Dose escalation conducted via accelerated titration method for first 2 dose levels followed by 3+3 method for remaining dose levels. Cohorts of 1 participant per dose level for first 2 dose levels. If at any time during cycle 1 there is an instance of pulmonary grade 2 toxicity or pulmonary function tests (PFT) decline\>10% related to study drug, current dose level expanded to 3 participants \& switched to 3+3 design. If neither of these nor any other DLT occur in dose levels 1-2, switch will be to the 3 + 3 design beginning with dose level 3. Three participants will be treated at dose level 3, if still no DLT, 3 more treated at dose level 4.

Dose limiting toxicities associated with the MTD of aerosol GCB using the NCI Common Terminology Criteria version 4 for Adverse Events (CTCAE) will be utilized for AE reporting. DLT defined as any of the following events that are at least (possibly, probably or definitely) attributable to aerosol GCB. The observation period for the purposes of dose-escalation will be the first cycle of therapy.

DLT Definition includes:

* Any episode of respiratory (bronchospasm, cough and/or dyspnea) grade 2 toxicity.
* or \> 10% decrease in FEV1 that persists \> 3 days after the drug is stopped or recurrent episode of respiratory (bronchospasm, cough and/or dyspnea) grade 2 toxicity.
* Any grade 3 or 4 non-hematological toxicity.
* Any grade 4 neutropenia or thrombocytopenia.

Assessment of serum levels of Gemcitabine (GCB) for evidence of spillover into the circulation and correlate with presence or absence of toxicity.

Response evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

James B. and Lois R. Archer Charitable Foundation

Gateway for Cancer Research

Nervous System Diseases

Pain

Shoulder Pain

Arthralgia

Joint Diseases

Neurologic Manifestations

Neostigmine

Cholinesterase Inhibitors

Enzyme Inhibitors

Cholinergic Agents

Neurotransmitter Agents

Deep Neuromuscular Blockade (NMB) given during surgery.

Sugammadex intravenously as a single bolus injection after surgery.

Pain assessment done at about 15, 45, and 90 minutes after surgery.

Moderate Neuromuscular Blockade (NMB) given during surgery.

Neostigmine intravenously slowly over a period of at least 1 minute after surgery.

Pain assessment done at about 15, 45, and 90 minutes after surgery.

Deep Neuromuscular Blockade (NMB) given during surgery.

Deep Neuromuscular Blockade (NMB)

Moderate Neuromuscular Blockade (NMB) given during surgery.

Moderate Neuromuscular Blockade (NMB)

4 mg/Kg, intravenously as a single bolus injection after surgery.

Sugammadex

70 mcg/Kg up to a total of 5 mg, intravenously slowly over a period of at least 1 minute after surgery.

Pain assessment done at about 15, 45, and 90 minutes after surgery.

Pain Assessment

Wendell H. Williams III, MD

Insufflation pressure (IP) is the creation of a pressure barrier of air/gas within the abdomen to allow the surgeon more space to work during abdominal surgery. Shoulder pain is a common complaint from patients who have had abdominal surgery and the pain is thought to be related to the use of IP.

In addition to anesthesia (which keeps you asleep during surgery), the current standard practice is to block the nerve-muscle junction with a type of drug called neuromuscular blockade (NMB) which paralyzes the abdominal muscles. This means that a lower level of insufflation pressure is needed by the surgeon.

To reverse the effects of NMB after surgery, a drug called neostigmine is given.

The goal of this clinical research study is to compare the use of standard-of-care moderate NMB and neostigmine to the use of deep NMB and a drug called Sugammadex when given to elderly patients (patients who are 65 years of age or older) who are scheduled to have robotic abdominal surgery. "Deep" and "moderate" in this study refers to the dose or strength of the NMB given.

This is an investigational study. Sugammadex and neostigmine are FDA approved and commercially available for the reversal of NMB. It is considered investigational to compare Sugammadex and neostigmine to learn if the use of one or the other in elderly patients can reduce the level of shoulder pain after surgery.

Up to 100 participants will be enrolled in this study. All will take part at MD Anderson.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups before your surgery. This is done because no one knows if one group is better, the same, or worse than the other.

* In Group 1, you will receive deep NMB and Sugammadex.
* In Group 2, you will receive moderate NMB and neostigmine.

Neither you nor the surgeon or surgical staff will know to which group you have been assigned. The surgeon will not know which group you are in because researchers want to learn how much, if at all, the surgeon needs to adjust the insufflation pressure during surgery. However, if needed for your safety, the surgeon will be able to find out which group you are in.

For your safety, the anesthesiologist will know to which group you have been assigned.

Surgery and Study Drug Administration:

After you have been assigned to a study group, you will have your surgery as scheduled. You will sign a separate consent form for surgery which describes the procedure and its risks in more detail. You will also sign a separate consent form to receive anesthesia.

Before your surgery, blood (about 2 teaspoons) will be drawn for biomarker testing. Biomarkers are found in the blood/tissue and may be related to the status of the disease and/or your reaction to the study drug(s).

During the surgery, the insufflation pressure that is being used, including any changes that are made to the pressure, will be recorded. After the surgery has been completed, you will receive either Sugammadex or neostigmine by vein until the effects of the NMB have been reversed.

You will recover after surgery in the post-anesthesia care unit (PACU). At about 15, 45, and 90 minutes after your surgery, a PACU nurse will ask you about any shoulder pain you are feeling and if so, how intense the pain is. Information about how long you stay in the hospital after surgery and if you have any side effects after surgery (such as nausea/vomiting or shoulder pain) will also be collected from your medical record.

Follow-Up:

After 30 days after you leave the hospital, you will be called by a member of the study staff to ask how you are doing and if you have had any additional hospitalizations since leaving the hospital. This phone call should last about 5-10 minutes.

Length of Study Participation:

Your participation in this study will be over after completing the 30-day follow up phone call.

Neuromuscular Blockade on Shoulder Pain of Elderly

The Effect of Deep Neuromuscular Blockade With Sugammadex Reversal on Shoulder Pain of Elderly Patients Undergoing Robotic Surgery: A Single-Center Double-Blinded Randomized Controlled Trial

Visual Analog Scale (VAS) pain score (0-10) for shoulder pain recorded, where 0 means no pain and 10 means the worst pain ever experienced . Percentage of participants who experienced should pain.

Intra-abdominal insufflation time and pressure directed by the surgeon and recorded continuously by the clinical coordinator until the time of desufflation.

The patients will be started on a continuous Rocuronium intravenous infusion following intubation. Insert recommendations and Institutional Standards will be used for Rocuronium. For the DNMB group, the rate will be adjusted and boluses given to maintain 1-2 post tetanic responses during the pneumoperitoneum. NMB will be reversed with Sugammadex 4 mg/Kg, intravenously as a single bolus injection, at the end of the surgery. Percentage of measured contraction strength of the fourth stimulus compared to the first stimulus.

Determined by the Dansk Selskab for Anæstesiologi og Intensiv Medicin(DASAIM)discharge criteria.Pts considered ready to discharge when the sum of all categories is\<4 and no single category has a score of \>1.Sedation.0:Patient is fully awake.1: Patient is asleep,aroused by verbal stimulation.2:Patient is asleep, aroused by physical stimulation.3:Patient is asleep,cannot be aroused.Respiratory Rate.0:Respiratory rate\>10. 1: Snoring,10\< RR\<30. 2:R\<10 or RR\>30/min.3:Periods of apnea or obstructive patterns.Oxygen Saturation.0:SpO2 ≥ 94%.1:90%≤SpO2\<94%. 2:85%≤ SpO2 \< 90%.3:SpO2 \< 85%. Systolic Blood Pressure. 0:SBP ≥ 100mmHg.1:90mmHg≤SBP\< 100mmHg.2:80mmHg≤SBP\< 90mmHg or SBP\>220mmHg.3:SBP\<80mmHg.Heart Rate.0:50\<HR≤100.1:100\<HR≤120.2:40\<HR≤ 50 or 120\<HR≤130.3:HR\<40 or HR\>130.Pain at rest.0:No pain 1:Light pain.2:Moderate pain.3:Severe pain.Nausea.0:No nausea or vomiting.1:Light nausea or vomiting without previous nausea. 2:Moderate nausea and/or vomiting.3:Severe nausea and/or vomiting.

Degree of Post-Operative Nausea determined per Visual Analog Scale per nurse in Post-Anesthesia Care Unit (PACU).

The patients will be started on a continuous Rocuronium intravenous infusion following intubation. Insert recommendations and Institutional Standards will be used for Rocuronium. For the DNMB group, the rate will be adjusted and boluses given to maintain 1-2 post tetanic responses during the pneumoperitoneum. NMB will be reversed with Sugammadex 4 mg/Kg, intravenously as a single bolus injection, at the end of the surgery.

Deep Neuromuscular Blockade (NMB) + Sugammadex

The patients will be started on a continuous Rocuronium intravenous infusion following intubation. Insert recommendations and Institutional Standards will be used for Rocuronium. For the MNMB group, the Rocuronium infusion rate will be adjusted to maintain 1-2 TOF responses and will be reversed with Neostigmine 70 mcg/Kg up to a total of 5 mg, intravenously slowly over a period of at least 1 minute, at the end of surgery.

Moderate Neuromuscular Blockade (NMB) + Neostigmine

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Body mass index (BMI)

Adjuvant or Immunotherapy

Dr. Wendell H. Williams III / Anesthesiology & Perioperative Medicine

Percentage of Patients Who Reported Shoulder Pain

Cumulative Intraoperative Insufflation Pressure

Percentage of Muscle Response Using Train-of-Four (TOF) in Post-Anesthesia Care Unit (PACU) to Measure Residual Muscle Relaxation

DASAIM at 15 min

DASAIM at 45 min

DASAIM at 90 min

Readiness to Discharge From the Post-Anesthesia Care Unit (PACU)

Nausea

Vomiting

Percentage of Participants With Nausea and/or Vomiting in PACU

Optimal

Good

Acceptable

Poor

Surgical Exposure Grading

Length of Hospital Stay

Overall Study

Urinary Bladder Diseases

Anticonvulsants

Adjuvants, Anesthesia

Central Nervous System Depressants

Rocuronium

Bromides

Glycopyrrolate

Neuromuscular Nondepolarizing Agents

Neuromuscular Blocking Agents

Anesthetics

Muscarinic Antagonists

Cholinergic Antagonists

Participants to have cystoscopy with bladder tumor resection.

Rocuronium used to induce the neuromuscular blockade and given in a rapid sequence for endotracheal intubation at a dose of 0.45 mg/kg of Ideal Body Weight. If maintenance is needed for continued relaxation then a dose of 0.15 mg/kg of Ideal Body Weight repeated as necessary.

Sugammadex administered as a single bolus, intravenous injection. The amount used is based on the patient's weight. A dose of 4 mg/kg used if recovery has reached at least 1-2 post-tetanic counts (PTC) following Rocuronium induced blockade.

Participants to have cystoscopy with bladder tumor resection.

Rocuronium used to induce the neuromuscular blockade and given in a rapid sequence for endotracheal intubation at a dose of 0.45 mg/kg of Ideal Body Weight. If maintenance is needed for continued relaxation then a dose of 0.15 mg/kg of Ideal Body Weight repeated as necessary.

Neostigmine/Glycopyrrolate administered as a single bolus, intravenous injection. The amount used is based on the patient's weight. Once T1 is at 10% or greater, a dose of 70 mcg/kg of Neostigmine with 14 mcg/kg Glycopyrrolate administered simultaneously over a period of one minute up to 5 mg.

Experimental: Sugammadex Participants to have cystoscopy with bladder tumor resection. Rocuronium used to induce the neuromuscular blockade and given in a rapid sequence for endotracheal intubation at a dose of 0.45 mg/kg of Ideal Body Weight. If maintenance is needed for continued relaxation then a dose of 0.15 mg/kg of Ideal Body Weight repeated as necessary.

Sugammadex administered as a single bolus, intravenous injection. The amount used is based on the patient's weight. A dose of 4 mg/kg used if recovery has reached at least 1-2 post-tetanic counts (PTC) following Rocuronium induced blockade.

70 mcg/kg by vein to reverse the muscle relaxation.

14 mcg/kg by vein to reverse the muscle relaxation.

Farzin Goravanchi, DO

The goal of this clinical research study is to determine whether using sugammadex, given with a standard muscle relaxation drug during bladder surgeries, improves anesthesia conditions and recovery time.

During some bladder operations, your muscles must be completely relaxed. Muscle relaxation drugs cause the muscles to relax, including the respiratory muscles, and as a result artificial ventilation is needed to help you breathe. Sugammadex and other standard drugs reverse the effect of the muscle relaxation drugs, allowing you to breathe on your own after the operation.

Study Groups:

If you agree to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. This is done because no one knows if one study group is better, the same, or worse than the other group:

* If you are in Group 1, you will receive sugammadex to reverse the muscle relaxation.
* If you are in Group 2, you will receive the standard of care (neostigmine/glycopyrrolate) to reverse the muscle relaxation.

You and the surgeon will not know which group you have been assigned to. However, the anesthesiologist and study staff will know.

Length of Study:

You will be on study for up to 1 week after the cystoscopy. If you are unable to have the procedure performed, you may be taken off study early.

This is an investigational study. Sugammadex and neostigmine/glycopyrrolate are all FDA approved and commercially available to reverse muscle relaxation. The comparison of these drugs is investigational.

Up to 50 participants will take part in this study. All will be enrolled at MD Anderson.

Study Procedures:

Before the cystoscopy, we will collect your basic information and medical history. We will take your vital signs and the anesthesiologist will perform routine assessments. This will take about 30-60 minutes to complete.

Before the cystoscopy, you will be given rocuronium to relax your muscles. After the procedure, you will receive either sugammadex or the standard of care to reverse the relaxation.

After you are extubated (the tube is removed from your throat), we will assess how fast the relaxation drugs the anesthesiologist gave you wear off (stop working), using a small monitoring device that will be attached to your wrist. This is the only research test that will be done right after surgery.

If you are still in the hospital 1 day after the cystoscopy, a member of the staff will ask you the series of questions. If you have been sent home, you will be called and you will complete them by phone.

Researchers will also collect information about your cystoscopy procedure and recovery from your medical record. This collection will continue for up to 1 week after surgery.

Investigation of Sugammadex in Outpatient Urological Procedures

A Phase IV Investigation of Sugammadex in Outpatient Urological Procedures

The primary outcome is to determine if Sugammadex can improve muscle recovery time, measured by time from administration of neuromuscular blockade reversal to train-of-four ratio of 0.9 in outpatient bladder procedures. It was assessed in the intraoperative period measuring the time from administration of reversal agent to TOF of 0.9 in minutes.

To determine if Sugammadex can improve post-operative complications for outpatient bladder procedures such as bladder perforation, nausea, vomiting, post-operative intubation and hospital admittance secondary to respiratory complications which was assessed uring follow ups on post-operative day 1 (POD1) and post-operative day 7 (POD7) looking for immediate postoperative complications such as bladder perforation, nausea, vomiting, postoperative intubation and hospital admittance secondary to respiratory complications and readmission within a week post-procedure for any other cause.

To determine if Sugammadex can improve overall recovery time, measured by time from end of surgery to the time patient met Discharge Criteria.

Sugammadex will be administered as a single bolus, intravenous injection. The amount used is based on the patient's weight. A dose of 4 mg/kg will be used if recovery has reached at least 1-2 post-tetanic counts (PTC) following Rocuronium induced blockade.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pembrolizumab With Intratumoral Injection of Clostridium Novyi-NT	NCT03435952	Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl...	Pembrolizumab Clostridium Nov... Doxycycline	18 Years -	M.D. Anderson Cancer Center
Oral Supplementation to Enhance Recovery Pilot Study	NCT03204266	Malignant Neopl...	Arginine recove... Omega-3 Fatty A...	18 Years -	M.D. Anderson Cancer Center
Study of Aerosol Gemcitabine in Patients With Solid Tumors and Pulmonary Metastases	NCT03093909	Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Melanoma and Ot...	Gemcitabine	12 Years - 50 Years	M.D. Anderson Cancer Center
Neuromuscular Blockade on Shoulder Pain of Elderly	NCT03210376	Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl...	Deep Neuromuscu... Moderate Neurom... Sugammadex Neostigmine Pain Assessment	65 Years -	M.D. Anderson Cancer Center
Investigation of Sugammadex in Outpatient Urological Procedures	NCT03138967	Malignant Neopl... Bladder Cancer	Rocuronium Sugammadex Neostigmine Glycopyrrolate	18 Years -	M.D. Anderson Cancer Center
Investigation of Sugammadex in Outpatient Urological Procedures	NCT03138967	Malignant Neopl... Bladder Cancer	Rocuronium Sugammadex Neostigmine Glycopyrrolate	18 Years -	M.D. Anderson Cancer Center
Oral Supplementation to Enhance Recovery Pilot Study	NCT03204266	Malignant Neopl...	Arginine recove... Omega-3 Fatty A...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for malignant neoplasms of urinary tract