VB-111 in Combination With Nivolumab in People With Metastatic Colorectal Cancer (mCRC)

Colorectal Neoplasms Clinical Trial

Official title: Phase II Trial of VB-111 in Combination With Nivolumab in Patients With Metastatic Colorectal Cancer (mCRC).

Status Completed

Clinical Trial Summary

Background:

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.

Objective:

To see if using a combination of Vascular Biogenics (VB)-111 and nivolumab is safe and will cause colorectal tumors to shrink.

Eligibility:

People ages 18 and older with microsatellite stable colorectal cancer that has spread to the liver

Design:

Participants must consent to sample collection protocol 11C0112.

Participants will be screened with:

Blood tests

Scans

Tumor samples. If these are not available, participants will have a biopsy.

Before they start treatment and with every treatment cycle, participants will have:

Physical exams

Blood tests

Heart tests

Before they start treatment and every 4 cycles, participants will have computed tomography (CT) or magnetic resonance imaging (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.

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Clinical Trial Description

Background:

• Immune based approaches in gastrointestinal (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.

• Vascular Biogenics (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 programmed cell death protein 1 (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.

Objectives:

• 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 in Solid Tumors (RECIST v1.1) of combined treatment of VB-111 and nivolumab in patients with refractory, metastatic CRC.

Eligibility:

• 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.

• Patient's 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.

Design:

• 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. ;

Related Conditions & MeSH terms

• Colorectal Cancer With Hepatic Metastases
• Colorectal Carcinoma
• Colorectal Neoplasms
• Colorectal Tumors
• Metastatic Colorectal Cancer

• NCT number: NCT04166383
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 2
• Start date: August 9, 2020
• Completion date: December 31, 2022