VB-111 in Combination With Nivolumab in People With Metastatic Colorectal Cancer (mCRC)
|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: NCT04166383|
Recruitment Status : Recruiting
First Posted : November 18, 2019
Last Update Posted : May 27, 2022
Gastrointestinal cancer is one of the most common cancers worldwide. Researchers think an unmet need exists to understand and improve treatment options. They want to see if a combination of drugs can help people with metastatic colorectal cancer.
To see if using a combination of VB-111 and nivolumab is safe and will cause colorectal tumors to shrink.
People ages 18 and older with microsatellite stable colorectal cancer that has spread to the liver
Participants must consent to sample collection protocol 11C0112.
Participants will be screened with:
Tumor samples. If these are not available, participants will have a biopsy.
Before they start treatment and with every treatment cycle, participants will have:
Before they start treatment and every 4 cycles, participants will have CT or MRI scans. For these, they will lie in a machine that takes pictures of the body. For the MRI, a soft padding or coil will be placed around their head.
Participants will have biopsies before they start therapy. They will have them again after 2 6 weeks on study.
On day 1 of 14-day cycles, participants will get one or both study drugs by vein.
After they finish treatment, participants will have monthly visits for 3 months. They will have a physical exam and blood tests.
If participants stop treatment for reasons other than their disease getting worse, they will have scans about every 8 weeks. This will continue until their disease gets worse.
Participants will be contacted by phone or email every 6 months. This will continue for life.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Colorectal Cancer Colorectal Neoplasms Colorectal Carcinoma Colorectal Cancer With Hepatic Metastases Colorectal Tumors||Biological: VB-111 Drug: Nivolumab||Phase 2|
- Immune based approaches in GI cancers have unfortunately- with the notable exception of immune checkpoint inhibition in microsatellite instable (MSI-H) disease and gastric cancer-been largely unsuccessful. The reasons for this are unclear but no doubt relate to the fact that in advanced disease GI cancer appears to be less immunogenic, as evidenced by the lack of infiltrating lymphocytes with advancing T stage as well as an immunosuppressive tumor micro environment.
- VB-111 is an anti-angiogenic agent comprising of a nonreplicating E1 deleted adenovirus type 5 which contains a modified murine preproendothelin (PPE) promoter and Fas-chimera transgene
- VB-111 has been tested and shows promise in glioblastoma, ovarian and thyroid tumors
- Nivolumab is a human monoclonal antibody directed against PD-1.
- The aim of this study is to study the effects of VB-111 in colorectal cancer (CRC) and to evaluate whether the antitumor immunity induced by VB-111 therapy can be enhanced by PD-1 inhibition.
- To determine the safety and tolerability of VB-111 in combination with nivolumab in patients with refractory, metastatic CRC
- To determine Best Overall Response (BOR) (partial response (PR) + complete response (CR)) according to Response Evaluation Criteria (RECIST v1.1) of combined treatment of VB-111 and nivolumab in patients with refractory, metastatic CRC.
- Histopathological confirmation of colorectal cancer metastatic to the liver
- Patients must have progressed on > 2 lines of standard of care chemotherapy for colorectal cancer or been intolerant of chemotherapy or refused prior chemotherapy.
- Patients tumors must be documented to be microsatellite stable (MSS).
- Patients must have at least 1 focus of metastatic disease that is amenable to pre-and on-treatment biopsies and be willing to undergo this.
- All patients enrolled will be required to have measurable disease by RECIST v 1.1 criteria.
- The proposed study is a phase II study of VB-111 in combination with immune checkpoint inhibition (nivolumab) in patients with metastatic CRC
- Treatment will be delivered in cycles consisting of 2 weeks with VB-111 given every 6 weeks and nivolumab given every 2-week until progression or unacceptable toxicity.
- Disease status evaluation will be done every 8 (+/- 1) weeks after the start of study therapy.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Trial of VB-111 in Combination With Nivolumab in Patients With Metastatic Colorectal Cancer (mCRC).|
|Actual Study Start Date :||August 9, 2020|
|Estimated Primary Completion Date :||December 31, 2022|
|Estimated Study Completion Date :||December 31, 2022|
Experimental: 1/Arm 1
VB-111 and nivolumab
1E13 or 0.7E13 VP via IV infusion on Day 1 of cycle 1 and continue every 6 weeks
240 mg of nivolumab via IV infusion on Day 1 of each cycle starting on cycle 2 and continue every 2 weeks
- To determine the safety and tolerability of VB-111 in combination with immune checkpoint inhibition (anti-PD-1) in patients with refractory, metastatic CRC [ Time Frame: 90 days after treatment ]List of adverse event frequency
- To determine Best Overall Response (BOR) [ Time Frame: every 8 weeks ]Proportion of patients whose tumors shrunk after therapy
- To evaluate progression-free survival (PFS). [ Time Frame: at progression ]Kaplan-Meier method, and the median PFS will be reported along with 95% confidence intervals
- To evaluate overall survival (OS) [ Time Frame: death ]Kaplan-Meier method, and the median OS will be reported along with 95% confidence intervals
- To evaluate a 6-month progression-free survival (PFS) [ Time Frame: 6 months ]Kaplan-Meier method, and the median PFS will be reported along with 95% confidence intervals
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04166383
|Contact: Donna M Hrones, C.R.N.P.||(240) firstname.lastname@example.org|
|Contact: Tim F Greten, M.D.||(240) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Tim F Greten, M.D.||National Cancer Institute (NCI)|