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

Infections

Papilloma

Virus Diseases

Neoplasms, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Dose Escalation Phase:

Starting dose of Alisertib: 30 mg by mouth 2 times a day on Days 1 - 7 each 21 day cycle.

Starting dose of TAK-228: 1 mg by mouth daily Days 3 - 18, with the exception of 2 mg daily Days 3 - 7 and 10 - 14 schedule in a 21 day cycle.

Dose Expansion Phase:

Alisertib and TAK-228 taken at the maximum tolerated dose from Dose Escalation Phase.

Dose Escalation Phase:

Starting dose of Alisertib: 30 mg by mouth 2 times a day on Days 1 - 7 each 21 day cycle.

Dose Expansion Phase: Maximum tolerated dose from Dose Escalation Phase.

Alisertib

Dose Escalation Phase:

Starting dose of TAK-228: 1 mg by mouth daily Days 3 - 18, with the exception of 2 mg daily Days 3 - 7 and 10 - 14 schedule in a 21 day cycle.

Dose Expansion Phase: Maximum tolerated dose from Dose Escalation Phase.

TAK-228

Siqing Fu, MD, PHD

The goal of this clinical research study is to find the highest tolerable dose of the combination of alisertib and TAK-228 that can be given to participants with advanced solid tumors that are associated with HPV. Researchers also want to learn if the study drug combination can help to control advanced solid tumors.

Study Groups:

If participant is found to be eligible to take part in this study, they will be assigned to a dose level based on when they join the study. Up to 5 dose levels of alisertib and TAK-228 will be tested. 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 were seen. This will continue until the highest tolerable dose of alisertib and TAK-228 is found.

Up to 14 participants will be enrolled onto a Dose Expansion group after the highest tolerable dose combination has been found.

Study Drug Administration:

Each cycle is 21 days.

On Days 1-7 of each cycle, participant will take alisertib by mouth 2 times a day with a glass of water (about 4 ounces).

On Days 3-18 of each cycle, participant will take TAK-228 by mouth 1 time a day Participant should not eat or drink anything for 2 hours before and 1 hour after taking TAK-228.

Study Visits:

Participant will need to take their blood sugar levels every morning while they are on study. Participant will be given a blood sugar monitor and the study staff will show them how to use it. Participant will also have their blood sugar tested in the clinic Participant must fast for at least 8 hours before each of these blood sugar tests. If the doctor thinks it is in participant's best interest, this testing may be decreased to 1 time a week after the first 2 months.

During Week 1 of Cycle 1:

* Participant will have a physical exam.
* Blood (about 3 teaspoons) will be drawn for routine tests and to test blood clotting, participant's blood fat levels, and their blood sugar levels.
* Urine will be collected for routine tests

On Day 1 of Cycles 1 and 2, you will have an EKG.

One (1) time during Weeks 2 and 3 of Cycle 1, blood (about 2 teaspoons) for routine tests and to test participant's blood sugar.

One (1) time a week during Cycles 1 and 2, blood (about 2 teaspoons) will be drawn for routine tests.

During Week 1 of Cycle 2 and beyond:

* Participant will have a physical exam.
* Urine will be collected for routine tests.

During Week 1 of Cycle 3 and beyond, blood (about 4 teaspoons) will be drawn routine tests and to test blood clotting, participant's blood fat levels, and their blood sugar levels.

During Cycles 2, 4, and 6 and then every 3 cycles, participant will have a CT, MRI, or positron emission tomography (PET) scan to check the status of the disease.

Length of Study:

Participant may continue taking the study drugs for as long as they are benefitting. Participant will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, if the doctor thinks it is in their best interest, if the study is stopped, if they need treatment that is not allowed on this study, or if they are unable to follow study directions.

Patient's participation on the study will be over after the end-of-study visit.

End of Study Visit:

Within 30 days of participant's last dose of study drugs:

* Participant will have an EKG to check your heart function.
* Participant will have a physical exam.
* Urine will be collected for routine tests.
* Blood (about 3 teaspoons) will be drawn for routine tests and to test blood clotting, participant's blood fat levels, and their blood sugar levels.
* Participant will have a CT, MRI, or PET scan to check the status of the disease.

This is an investigational study. Alisertib and TAK-228 are not FDA approved or commercially available. They are currently being used for research purposes only.

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

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

Alisertib and TAK-228 in Participants With Human Papilloma Virus (HPV) Associated Malignancies

A Phase I Study of Alisertib and TAK-228 in Participants With Human Papilloma Virus (HPV) Associated Malignancies

Maximum tolerated dose (MTD) defined by dose limiting toxicities (DLTs) that occur within the initial cycle (21 days).

Clinical benefit categorized by RECIST 1.1.

Millennium Pharmaceuticals, Inc.

Musculoskeletal Diseases

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

Ovarian Neoplasms

Ovarian Cancer

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Dose Escalation Phase: Participants take both Selumetinib and Olaparib by mouth 2 times each day, about 12 hours apart at the Starting Dose Level. Treatment cycle is 28 days.

When maximum tolerated dose reached, Dose Expansion Phase begins.

Dose Expansion Phase: Selumetinib + Olaparib taken at the maximum tolerated dose from Dose Escalation Phase.

Dose Escalation Phase Starting Dose: 50 mg by mouth twice a day on Days 1-28.

Dose Expansion Phase Starting Dose: Maximum tolerated dose from Dose Escalation Phase.

Selumetinib

Dose Escalation Phase Starting Dose: 150 mg by mouth twice a day on Days 1-28.

Dose Expansion Phase Starting Dose: Maximum tolerated dose from Dose Escalation Phase.

Shannon Westin, MD

This study has 2 phases: Phase 1 (dose escalation) and Phase 2 (dose expansion).

The goal of Phase 1 of this clinical research study is to find the highest tolerable dose combination of selumetinib and olaparib that can be given to patients who have solid tumors that are advanced or recurrent (has returned after treatment).

The goal of Phase 2 is to learn if the highest tolerable dose combination found in Phase 1 can help to control advanced or recurrent solid tumors.

The safety of the study drug combination will also be studied in both parts.

This is an investigational study. Selumetinib is not FDA approved or commercially available. It is currently being used for research purposes only. Olaparib is FDA approved and commercially available for the treatment of ovarian cancer that has a certain type of genetic mutation (change). It is considered investigational to use selumetinib in combination with olaparib to treat advanced or recurrent cancer.

The study doctor can explain how the study drugs are designed to work. Up to 90 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 assigned to a phase depending on when you join the study. Up to 30 participants will be enrolled in Phase 1, and up to 60 participants will be enrolled in Phase 2.

If you are enrolled in Phase 1, the dose of the study drugs you receive will depend on when you join this study. Up to 3 dose level combinations of selumetinib and olaparib will be tested. The first group of participants will receive the lowest dose level of each study drugs. Each new group will receive a higher dose of either selumetinib or olaparib study drugs than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose combination of the study drugs is found.

If you are enrolled in Phase 2, you will receive the highest study drug combination that was tolerated in Phase 1.

Study Drug Administration:

Each study cycle is 28 days.

You will take both selumetinib and olaparib by mouth 2 times each day, about 12 hours apart (1 dose in the morning, 1 dose in the evening). You should fast (have nothing to eat or drink except water) for at least 2 hours before and 1 hour after your dose. If you vomit or miss a dose, you should not retake the dose. Wait and take your next scheduled dose.

Depending on the dose level of selumetinib you are receiving, you may only take the study drug on Days 1-5 of each week. The study doctor will tell you how often you should take selumetinib.

You will be given a study drug diary to record when you take each dose. The study staff will show you how to fill it out.

You will wait to take your morning dose of study drugs at the clinic on certain days. The study staff will remind you before each of these clinic visits.

Length of Treatment:

You may continue to receive the study drugs for as long as the study doctor thinks it is in your best interest. You will no longer be able to receive the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your active participation on the study will be over after the 30-day follow-up visit; however, you will be contacted by phone every 3 months to check on you and the status of the disease.

Study Visits:

On Days 1 and 15 of Cycle 1:

* You will have a physical exam
* Blood (about 3 tablespoons) will be drawn for routine and PD testing.
* If you are in Phase 1, part of this sample on Day 1 will be used for pharmacokinetic (PK) testing. PK testing measures the amount of study drug in the body at different time points.
* If you are in Phase 2, part of this sample will be used for tumor marker testing.
* You will have an EKG.
* On Day 15, if you are in Phase 2, you will have a tumor biopsy for PD testing, including genetic testing.

On Day 8 of Cycle 1:

* You will have a physical exam.
* Blood (about 3 tablespoons) will be drawn for routine and PD tests. If you are in Phase 2, part of this sample will be used for tumor marker testing.
* You will have an EKG.

On Day 22 of Cycle 1:

* You will have a physical exam.
* Blood (about 3 tablespoons) will be drawn for routine and PD tests. If you are in Phase 2 and have endometrial or ovarian cancer, part of this blood will be used for tumor marker testing.

On Day 1 of Cycle 2:

* You will have a physical exam.
* You will have an eye exam.
* Blood (about 3 tablespoons) will be drawn for routine and PD tests.
* If you are in Phase 1, part of this blood will be used for PK testing.
* If you are in Phase 2, part of this blood will be used for tumor marker testing.

On Day 26 of Cycle 2, you will have an MRI or a CT scan.

On Day 1 of Cycles 3 and beyond:

* You will have a physical exam
* Blood (about 3 tablespoons) will be drawn for routine and PD tests. If you are in Phase 2, part of this blood will be used for tumor marker testing.

Starting on Day 1 of Cycle 4 and every 3 cycles after that, you will have an ECHO.

During Cycles 4 and 6 and then every 3 cycles after that (Cycles 9, 12, 15, and so on), you will have MRI or a CT scan.

At any time the study doctor thinks it is needed, you may have some or all of these tests repeated to check on your health.

End-of-Treatment Visit:

Within 7 days after your last dose of study drugs:

* You will have a physical exam.
* Blood (about 3 tablespoons) will be drawn for routine and PD tests.
* If it has been more than 28 days since the last scan, you will have an MRI or CT scan.

Follow-Up:

About 30 days after your last study drug dose:

* You will have a physical exam.
* Blood (about 2 tablespoons) will be drawn for routine tests.

You may be called by a member of the study staff every 3 months to ask how you are doing and if you have had any side effects. This call should last about 5-10 minutes.

Selumetinib and Olaparib in Solid Tumors

Evaluation of the Combination of Selumetinib and Olaparib in Endometrial, Ovarian and Other Solid Tumors With Ras Pathway Alterations, and Ovarian Tumors With PARP Resistance

MTD defined by dose limiting toxicities (DLTs) that occur during the first 4 weeks of therapy and are related to the study medications. Grading of DLTs follow the guidelines provided in the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Samples for determination of drug concentration in selumetinib and olaparib analyzed using an appropriate bioanalytical method.

Two sample t-test with a 2-sided significance level of 0.05 used to compare baseline expression values with differing treatment responses.

We will tabulate tumor response and objective response rate (ORR), as well as clinical benefit rate (objective response or stable disease for 4 months) with 95% confidence intervals. We will estimate the median PFS with a 95% confidence interval. All outcomes will first be evaluated in each expansion cohort separately, and then will be evaluated in a combined analysis that includes all expansion cohort patients.

AstraZeneca

Patients with late malignant digestive tract tumor, for example metastatic colorectal cancer, pancreatic cancer, gastric cancer and so on. because of this is a open, single arm trail, there is no control group.

Patients with advanced malignant gastrointestinal tumors were injected with CART cells

gucy2c cart cells

Weijia Fang

Ict-gc is an open, single-center study to evaluate the safety and efficacy of CAR-T-targeted therapy in patients with advanced gastrointestinal tumors.

The primary objective of phase 1 is to evaluate the safety of CART regimens. The primary objective of phase 2 is to evaluate the efficacy of CART, as measured by objective response rate in subjects with colorectal cancer. Secondary objectives will include assessing the safety and tolerability of CART and additional efficacy endpoints.

CART Therapy in GUCY2C-positive Digestive Tract Tumors

Clinical Study on the Safety and Efficacy of CART Cells in the Treatment of Advanced GUCY2C-positive Digestive Tract Tumors

The investigator is responsible for ensuring that all adverse events observed by the investigator or reported by the subject during the 3-month period from enrollment (i.e. initiation of leukocyte separation) to 3 months after targeted car-t infusion are monitored and reported. After three months, researchers will be required to monitor and report targeted adverse events, including neurological, blood, infection, autoimmune diseases, and secondary malignant tumors, for 24 months or until disease progression, whichever occurs first.

We will summarize the classification of cytokine release syndrome (CRS) according to the severity and system organ classification.

Remission will be evaluated by the central investigator at the time indicated in the evaluation plan. The disease was evaluated according to the response evaluation criteria in solid tumors RECIST version 1.1 or EORTC or percist. Flow cytometry, molecular or cytogenetic studies used in the trial will be used to assist, but will not be used alone to determine remission.

Innovative Cellular Therapeutics Co., Ltd.

Weijia Fang, MD

director

Digestive System Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Yifu He

Daiyan Liu

Yifu he

Chimeric Antigen Receptor T Cells (CART) Therapy in GUYC2C postive Digestive system tumors, include colorectal cancer, gastric cancer, liver cancer, pancreatic cancer, adenocarcinoma of esophagus, cancer of the esophagogastric junction.

Ict-gc is an open, single-center study to evaluate the safety and efficacy of CAR-T-targeted therapy in patients with advanced gastrointestinal tumors.

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
Alisertib and TAK-228 in Participants With Human Papilloma Virus (HPV) Associated Malignancies	NCT02812056	Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl...	Alisertib TAK-228	18 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
Selumetinib and Olaparib in Solid Tumors	NCT03162627	Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl...	Selumetinib Olaparib	18 Years -	M.D. Anderson Cancer Center
CART Therapy in GUCY2C-positive Digestive Tract Tumors	NCT04652219	Malignant Neopl...	gucy2c cart cel...	18 Years - 70 Years	Zhejiang University
CART Therapy in Digestive System Tumors	NCT04780529	Malignant Neopl...	gucy2c cart cel...	18 Years - 70 Years	Innovative Cellular Therapeutics Co., Ltd.
CART Therapy in Digestive System Tumors	NCT04780529	Malignant Neopl...	gucy2c cart cel...	18 Years - 70 Years	Innovative Cellular Therapeutics Co., Ltd.
Study of Durvalumab (MEDI4736) (Anti-PD-L1) and Trametinib (MEKi) in MSS Metastatic Colon Cancer	NCT03428126	Malignant Neopl... Colorectal Canc... Colon Cancer	Durvalumab Trametinib	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for malignant neoplasms of digestive organs