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

Respiratory Tract (Lung and Bronchial) Diseases

Pleural Effusion

Pleural Effusion, Malignant

Pleural Diseases

Respiratory Tract Diseases

Pleural Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Adjuvants, Anesthesia

Analgesics

Central Nervous System Depressants

Fentanyl

Analgesics, Opioid

Narcotics

Anesthetics

Anesthetics, Intravenous

Anesthetics, General

Symptom and quality of life questionnaires completed at baseline and at 10 - 14 days after receiving Saline. Participant given a Fentanyl patch which should be worn at follow up visit 5 days after IPC placement. Fentanyl patch then be removed and Fentanyl by vein given prior to catheter draining. Study staff drains the IPC and places Saline in the catheter.

After the IPC is removed, participant is called one time each month by study staff to check on their status.

Symptom and quality of life questionnaires completed at baseline and at 10 - 14 days after receiving Doxycycline. Participant given a Fentanyl patch which should be worn at follow up visit 5 days after IPC placement. Fentanyl patch then be removed and Fentanyl by vein given prior to catheter draining. Study staff drains the IPC and places Doxycycline in the catheter.

After the IPC is removed, participant is called one time each month by study staff to check on their status

Symptom and quality of life questionnaires completed at baseline and at 10 - 14 days after receiving Saline or Doxycycline.

Questionnaires

Participant given a Fentanyl patch, 12 mcg/hour, which should be worn at follow up visit 5 days after IPC placement.

Fentanyl Patch

Fentanyl 50 mcg given by vein prior to catheter draining.

Fentanyl (IV)

Catheter is drained then Saline placed in the catheter. Catheter is capped for 1 hour and then drained again.

Saline

Catheter is drained then Doxycycline 500 mg placed in the catheter. Catheter is capped for 1 hour and then drained again.

After the IPC is removed, participant is called one time each month by study staff to check on their status.

Phone Calls

David Ost, MD

The goal of this clinical research study is to compare indwelling pleural catheters (IPC) in combination with saline (the current standard of care) versus IPC in combination with doxycycline as treatment for pleural effusions.

IPC Placement and Placement Follow-Up:

Before the IPC is inserted, you will complete 2 questionnaires about your quality of life and any symptoms you may have. It should take no more than 15-20 minutes to complete. You will also have a chest x-ray and you will rate your pain on a scale of 1-10. These tests are all part of your standard of care and can be explained to you in more detail by your doctor. You will be required to sign a separate consent form in order to have the IPC placed. Your doctor will give you detailed instructions about the IPC placement procedure, including its risks.

After the IPC is placed, the doctor will give you a prescription for a fentanyl patch to help control pain. The study staff will tell you how and when to wear the fentanyl patch and about any side effects that are associated with fentanyl.

About 5 days (+/- 2 days) after the IPC has been placed, you will have a clinic visit where you will be checked up on as part of your standard of care. It is important that you wear your fentanyl patch in the morning before this visit. At this clinic visit, the results of a previously performed chest x-ray will be reviewed, you will be asked to rate your pain on a scale of 1-10, and you will be asked how much fluid has drained from your catheter.

Based on the results of the above Day 5 check-up, if you are found to be ineligible to receive the study drug, the fentanyl patch will be taken off and you will be followed as part of your usual care. However, you will still considered to be on study and you will be followed the same as a participant who receives the study drug.

If you are found to be eligible to receive the study drug, you will receive fentanyl by vein over a few minutes, if needed to help control your pain. The study staff will then begin to drain your catheter and either doxycycline or saline (described below) will be placed in the catheter. The catheter will be capped for 1 hour and then drained again.

To determine if you will receive doxycycline or saline, 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 doxycycline.
* If you are in Group 2, you will receive saline.

Neither you nor the study doctor will know if you are receiving doxycycline or saline. However, if needed for your safety, the study staff will be able to find out what you are receiving.

Length of Study Participation:

You will receive doxycycline or saline 1 time on this study. Your participation on this study will be over if you withdraw consent or the study closes, whichever takes place first.

Follow-Up:

Between 10-14 days after you have received either doxycycline or saline, you will come to the clinic as part of your usual standard of care so the doctor can check your IPC for possible leaking, infection, to see how much fluid has drained, and to remove any sutures. The catheter may be removed if you have it is leaking or shows signs of infection. You will continue to have this visit 1 time each month as part of your standard of care until the catheter is removed. During each of these visits:

* You will have a chest x-ray to check the status of your lungs.
* You will complete the same 2 questionnaires that you completed before your IPC was placed.

Long-Term Follow-Up:

One (1) time each month after the IPC is removed, you will be called and asked how you are doing, if you are having any side effects, if the disease has come back, and about your overall quality of life. Some of this information may be collected from your medical record. Each phone call should last about 5-10 minutes.

This is an investigational study. Doxycycline is FDA approved and commercially available for the treatment of different types of infections and pleural effusions. It is considered investigational to compare doxycycline to saline to treat pleural effusions.

Up to 250 participants will take part in this study. All will be enrolled at MD Anderson.

Indwelling Pleural Catheter With Either Doxycycline or Saline at Day 7 for Pleurodesis

A Double Blind Randomized Controlled Trial of Indwelling Pleural Catheters Versus Indwelling Pleural Catheters Plus Doxycycline Pleurodesis for Treatment of Malignant Pleural Effusions

This outcome will be analyzed by cause-specific hazard Cox model with treatment group as a covariate. Whenever a catheter is removed the cause for removal will be documented. For the analysis causes will include removal due to decreased drainage (i.e. as per plan) as well as removal due to complications (e.g. infection, empyema, and refractory pain) or other reasons (e.g. catheter plugged but no complication to the patient, patient preference without a complication).

Due to slow accrual and the design of the study the protocol was terminated and Adverse Events was not collected.

Symptom and quality of life questionnaires completed at baseline and at 10 - 14 days after receiving Saline. Participant given a Fentanyl patch which should be worn at follow up visit 5 days after IPC placement. Fentanyl patch then be removed and Fentanyl by vein given prior to catheter draining. Study staff drains the IPC and places Saline in the catheter. After the IPC is removed, participant is called one time each month by study staff to check on their status. Questionnaires: Symptom and quality of life questionnaires completed at baseline and at 10 - 14 days after receiving Saline or Doxycycline.

Fentanyl Patch: Participant given a Fentanyl patch, 12 mcg/hour, which should be worn at follow up visit 5 days after IPC placement.

Fentanyl (IV): Fentanyl 50 mcg given by vein prior to catheter draining.

Saline: Catheter is drained then Saline placed in the catheter. Catheter is capped for 1 hour and then drained again.

Phone Calls: After the IPC is removed, partici

Indwelling Pleural Catheters (Randomized to Saline)

Symptom and quality of life questionnaires completed at baseline and at 10 - 14 days after receiving Doxycycline. Participant given a Fentanyl patch which should be worn at follow up visit 5 days after IPC placement. Fentanyl patch then be removed and Fentanyl by vein given prior to catheter draining. Study staff drains the IPC and places Doxycycline in the catheter.

After the IPC is removed, participant is called one time each month by study staff to check on their status. Questionnaires: Symptom and quality of life questionnaires completed at baseline and at 10 - 14 days after receiving Saline or Doxycycline.

Fentanyl Patch: Participant given a Fentanyl patch, 12 mcg/hour, which should be worn at follow up visit 5 days after IPC placement.

Fentanyl (IV): Fentanyl 50 mcg given by vein prior to catheter draining.

Doxycycline: Catheter is drained then Doxycycline 500 mg placed in the catheter. Catheter is capped for 1 hour and then drained again.

Phone Calls: After th

Indwelling Pleural Catheters Plus Doxycycline (Randomized to R

Indwelling Pleural Catheters (IPC) (Randomized to Saline)

IPC Plus Doxycycline (Randomized to Rx Arm)

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

2 participants withdrew before randomization

Due to slow accrual and the design of the study the protocol was terminated and no analysis or adverse event was reported.

Ost,David,M.D. / DOST@MDANDERSON.ORG

Symptom and quality of life questionnaires completed at baseline and at 10 - 14 days after receiving Saline. Participant given a Fentanyl patch which should be worn at follow up visit 5 days after IPC placement. Fentanyl patch then be removed and Fentanyl by vein given prior to catheter draining. Study staff drains the IPC and places Saline in the catheter.

After the IPC is removed, participant is called one time each month by study staff to check on their status.

Questionnaires: Symptom and quality of life questionnaires completed at baseline and at 10 - 14 days after receiving Saline or Doxycycline.

Fentanyl Patch: Participant given a Fentanyl patch, 12 mcg/hour, which should be worn at follow up visit 5 days after IPC placement.

Fentanyl (IV): Fentanyl 50 mcg given by vein prior to catheter draining. Saline: Catheter is drained then Saline placed in the catheter. Catheter is capped for 1 hour and then drained again.

Phone Calls: After the IPC is removed, partici

Indwelling Pleural Catheter (IPC) + Saline

Symptom and quality of life questionnaires completed at baseline and at 10 - 14 days after receiving Doxycycline. Participant given a Fentanyl patch which should be worn at follow up visit 5 days after IPC placement. Fentanyl patch then be removed and Fentanyl by vein given prior to catheter draining. Study staff drains the IPC and places Doxycycline in the catheter.

After the IPC is removed, participant is called one time each month by study staff to check on their status Questionnaires: Symptom and quality of life questionnaires completed at baseline and at 10 - 14 days after receiving Saline or Doxycycline.

Fentanyl Patch: Participant given a Fentanyl patch, 12 mcg/hour, which should be worn at follow up visit 5 days after IPC placement.

Fentanyl (IV): Fentanyl 50 mcg given by vein prior to catheter draining. Doxycycline: Catheter is drained then Doxycycline 500 mg placed in the catheter. Catheter is capped for 1 hour and then drained again.

Phone Calls: After th

Indwelling Pleural Catheter (IPC) + Doxycycline

Due to slow accrual and the design of the study the protocol was terminated. No data was collected and no analysis was done.

The Primary Outcomes of Interest Will be Time to Catheter Removal.

Due to slow accrual and the design of the study the protocol was terminated and no analysis was done.

Assessment of Symptom Burden, Pleurodesis Efficacy, Complications, Health Care Resource Utilization, the Need of Hospitalization for Pain Control, Pain Free Days and Mortality

On Day 5, Fentanyl patch 12 mcg/hr placed if not already on, Fentanyl 50 mcg IV given, drain maximally, saline instilled, catheter capped for 1 hour and then re-drain. Pain will assess using a Visual Analogue Scale (VAS) as well, patient discharged home.

Symptom and quality of life questionnaires will be completed at baseline, at 10 - 14 days and each month for 12 months as well as recurrence status defined as recurrent effusion on the same side requiring intervention will be documented.

On Day 5, Fentanyl patch 12 mcg/hr placed if not already on, Fentanyl 50 mcg IV given, drain maximally, doxycycline instilled, Catheter is capped for 1 hour and then re-drain. Pain will assess using a Visual Analogue Scale as well, patient discharged home.

Symptom and quality of life questionnaires will be completed at baseline, at 10 - 14 days and each month for 12 months as well as recurrence status defined as recurrent effusion on the same side requiring intervention will be documented.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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
Indwelling Pleural Catheter With Either Doxycycline or Saline at Day 7 for Pleurodesis	NCT02623959	Advanced Cancer... Malignant Pleur...	Questionnaires Fentanyl Patch Fentanyl (IV) Saline Doxycycline Phone Calls	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for periostat

Every month we try and update this database with for periostat cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for periostat

Every month we try and update this database with for periostat cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for periostat cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.