Pembrolizumab With Intratumoral Injection of Clostridium Novyi-NT
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03435952|
Recruitment Status : Recruiting
First Posted : February 19, 2018
Last Update Posted : February 27, 2023
|First Submitted Date ICMJE||February 9, 2018|
|First Posted Date ICMJE||February 19, 2018|
|Last Update Posted Date||February 27, 2023|
|Actual Study Start Date ICMJE||July 10, 2018|
|Estimated Primary Completion Date||October 1, 2024 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Maximum Tolerated Dose (MTD) of Intratumoral Injection of Clostridium Novyi-NT with Pembrolizumab [ Time Frame: 6 weeks ]
MTD defined as the highest dose studied in which the incidence of DLT was less than 33%.
|Original Primary Outcome Measures ICMJE||Same as current|
|Current Secondary Outcome Measures ICMJE
||Preliminary Anti-Tumor Activity of Pembrolizumab in Combination with C. novyi-NT in the Injected Tumor and an Overall Response by RECIST 1.1 [ Time Frame: 6 weeks ]|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Pembrolizumab With Intratumoral Injection of Clostridium Novyi-NT|
|Official Title ICMJE||A Phase Ib Investigation of Pembrolizumab in Combination With Intratumoral Injection of Clostridium Novyi-NT in Patients With Treatment-Refractory Solid Tumors|
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:
On Day 8:
On Days 9-15 daily:
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:
On Days 35:
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:
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):
Follow Up Visit:
About 30 days after your last dose of pembrolizumab:
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.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 1|
|Study Design ICMJE||Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Study Arms ICMJE||Experimental: Pembrolizumab + Clostridium novyi-NT
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
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE
|Original Estimated Enrollment ICMJE||Same as current|
|Estimated Study Completion Date ICMJE||October 1, 2024|
|Estimated Primary Completion Date||October 1, 2024 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT03435952|
|Other Study ID Numbers ICMJE||2017-0719
NCI-2018-00757 ( Registry Identifier: NCI CTRP )
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||Not Provided|
|Current Responsible Party||M.D. Anderson Cancer Center|
|Original Responsible Party||Same as current|
|Current Study Sponsor ICMJE||M.D. Anderson Cancer Center|
|Original Study Sponsor ICMJE||Same as current|
|PRS Account||M.D. Anderson Cancer Center|
|Verification Date||February 2023|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP