Standard of Care Alone or in Combination With Ad-CEA Vaccine and Avelumab in People With Previously Untreated Metastatic Colorectal Cancer QUILT-2.004

Colorectal Cancer Clinical Trial

Official title: A Randomized Phase II Trial of Standard of Care Alone or in Combination With Ad-CEA Vaccine and Avelumab in Patients With Previously Untreated Metastatic or Unresectable Colorectal Cancer

Status Terminated

Clinical Trial Summary

Background:

Colorectal cancer is a common cancer in the Unites States (U.S.) It causes the second most cancer-related deaths. The drug avelumab and vaccine Ad-CEA together help the immune system fight cancer.

Objective:

To test if avelumab and Ad-CEA plus standard therapy treats colorectal cancer that has spread to other sites better than standard therapy alone.

Eligibility:

People ages 18 and older with untreated colorectal cancer that has spread in the body

Design:

Participants will be screened with:

Test to see if their cancer has a certain deficiency

Blood, urine, and heart tests

Scans

Medical history

Physical exam

Tumor sample. This can be from a previous procedure.

A small group of participants will get Ad-CEA and avelumab plus standard therapy. This is leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX) plus bevacizumab for up to 24 weeks then capecitabine plus bevacizumab.

The others will have treatment in 2-week cycles. They will be Arm A or B:

Arm A: FOLFOX and bevacizumab by intravenous (IV) days 1 and 2 for 12 cycles. After that, capecitabine by mouth twice a day and bevacizumab by IV on day 1.

Arm B: Ad-CEA injection every 2-12 weeks. Avelumab by IV on day 1 of each cycle. FOLFOX and bevacizumab by IV days 2 and 3 for 12 cycles. Then, capecitabine by mouth twice a day and bevacizumab through IV on day 2.

Participants will repeat screening tests during the study.

Participants will be treated until their disease gets worse or they have bad side effects. Arm A participants can join Arm B. They will have a visit 4 5 weeks after they stop therapy.

Clinical Trial Description

Background

• Colorectal cancer (CRC) is the fourth most common cancer diagnosis in the United States and accounts for the second most cancer-related deaths.

• Programmed death ligand 1 (PD-L1) is a transmembrane protein that was first identified for its role in the maintenance of self-tolerance and prevention of autoimmunity. Blockade of the interaction between PD-L1 on tumor cells and PD-1 on T cells is expected to reverse T cell suppression within tumors. These agents are dependent on underlying T cell activation against the tumor cell to be effective.

• Avelumab is a fully human immunoglobulin G 1 (IgG1) anti-PDL1 antibody that selectively binds to PD-L1 and competitively blocks its interaction with PD-1.

• In ongoing phase 1 trials of avelumab, the agent has been well tolerated and has shown clinical activity.

• Clinical trials with anti-PD-1/L1 agents in colorectal cancer have resulted in minimal activity in patients who do not have mismatch repair deficiency (MMR-D).

• Therapeutic cancer vaccines targeting overexpressed proteins offer a potential method to activate T cells against tumors.

• A novel adenovirus-based, carcinoembryonic antigen (CEA)-targeting vaccine has demonstrated cytolytic T cell responses in patients with metastatic colorectal cancer.

• Standard of care agents in first line metastatic colorectal cancer (CRC) have properties been associated with improved immune response via immunologic cell death and immunogenic modulation.

Primary Objective

-To determine if there is an improvement progression free survival among patients with metastatic colorectal cancer lacking a mismatch repair deficiency who are treated with standard of care + anti- PDL1 monoclonal antibody + Ad-CEA therapeutic cancer vaccine compared with standard of care alone.

Eligibility

• Subject's age 18 and older with previously untreated pathologically confirmed metastatic or unresectable colorectal cancer; prior adjuvant therapy is acceptable.

• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.

• Normal organ and bone marrow function.

• Subjects with active autoimmune diseases requiring treatment and subjects requiring system steroids (except for physiologic doses for steroid replacement) are not allowed.

• Tumor sample and whole blood sample must be available for proteomics, genomics and transcriptomics analyses.

• Subjects with metastatic or unresectable colorectal cancer with mismatch repair deficiency (MMR-D or microsatellite instability (MSI)-High) will not be eligible.

Design

• This is a randomized, multicenter phase II clinical trial designed to evaluate the potential improvement in progression free survival (PFS) when Avelumab and Ad-CEA vaccine are used in combination with standard of care therapy in metastatic or unresectable colorectal cancer when compared with standard of care alone (FOLFOX-A).

• A lead in cohort, comprising the first 6 evaluable subjects enrolled, will be treated with avelumab + Ad- CEA vaccine + standard of care in order to assess the safety of the combination.

• If no more than 1 subject in the lead in cohort experiences a dose limiting toxicity attributable to the investigational new drug (IND) agents, 70 evaluable subjects will be randomized on a 1:1 basis to receive either Avelumab + Ad-CEA vaccine + standard of care (Arm B) or standard of care alone (Arm A).

• Standard of care therapy consists of 6 - 12 two-week cycles of bevacizumab + FOLFOX (5-FU, leucovorin, oxaliplatin) followed by two-week cycles of bevacizumab + capecitabine until disease progression.

• Subjects assigned to Arm A that have progressive disease will be offered Avelumab + Ad-CEA vaccine in combination with a standard chemotherapy regimen.

• Kaplan-Meier curves and a two-tailed log-rank test will be the primary analysis methods.

• The accrual ceiling for the study is set at 97. ;

Related Conditions & MeSH terms

• Colorectal Adenocarcinoma
• Colorectal Cancer
• Colorectal Carcinoma
• Colorectal Neoplasms
• Colorectal Tumors

• NCT number: NCT03050814
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Terminated
• Phase: Phase 2
• Start date: April 5, 2017
• Completion date: August 25, 2021