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

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

Ovarian Neoplasms

Ovarian Cancer

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme 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.

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
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
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

Spots Global Cancer Trial Database for malignant neoplasms of thyroid and other endocrine glands