Cetuximab and Pembrolizumab in Treating Patients with Colorectal Cancer That is Metastatic or Cannot Be Removed by Surgery

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase II, Phase IBiomarker/Laboratory analysis, TreatmentActive18 and overI 274515
NCI-2016-00228, NCT02713373

Trial Description

Summary

This phase I/II trial studies the side effects and best dose of cetuximab when given together with pembrolizumab in treating patients with colorectal cancer that has spread from the primary site (place where it started) to other places in the body (metastatic) or that cannot be removed by surgery. Monoclonal antibodies, such as cetixumab and pembrolizumab, may block tumor growth in different ways by targeting certain cells.

Further Study Information

PRIMARY OBJECTIVES:

I. To estimate the objective response rate of patients with metastatic colorectal cancer treated with pembrolizumab and cetuximab.

II. To estimate the 6-month progression free survival (PFS) rate of patients with metastatic colorectal cancer treated with pembrolizumab and cetuximab.

III. To examine the adverse event profile of combining pembrolizumab and cetuximab.

SECONDARY OBJECTIVES:

I. To examine the PFS of patients with metastatic colorectal cancer treated with pembrolizumab and cetuximab.

II. To determine the objective response rate by immune-related response criteria (irRC) of patients with metastatic colorectal cancer.

III. To examine the overall survival of patients with metastatic colorectal cancer treated with pembrolizumab and cetuximab.

TERTIARY OBJECTIVES:

I. Identify tumor and peripheral blood biomarkers of response and/or resistance to the study treatment.

OUTLINE:

Patients receive cetuximab intravenously (IV) over 120 minutes on day 1 of course 1 and over 60 minutes on days 1, 8 and 15 of subsequent courses. Patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients may continue pembrolizumab treatment for up to 1 year if they experience disease progression.

After completion of the study treatment, patients are followed up every 3 months for up to 2 years.

Eligibility Criteria

Inclusion Criteria:

Have a pathologically confirmed diagnosis of colorectal cancer, which is metastatic or otherwise unresectable

Have received at least 1 prior systemic therapy in the metastatic or unresectable disease setting; patients who have recurred within six months of adjuvant chemotherapy are not required to have received an additional line of chemotherapy

RAS wild-type; both KRAS and NRAS testing are necessary; the presence of pathogenic mutations in KRAS or NRAS is exclusionary; primary tumor or metastatic tumor may be tested

Naive to anti-EGFR therapy (cetuximab or panitumumab)

Have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2

Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present

Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion; newly-obtained is defined as a specimen obtained up to 30 days prior to initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the principal investigator

Hemoglobin >= 8 g/dL (performed within 14 days of treatment initiation)

Absolute neutrophil count >= 1000/mm^3 (performed within 14 days of treatment initiation)

Platelet count >= 100,000/mm^3 (performed within 14 days of treatment initiation)

Serum creatinine clearance >= 15 mL/min (performed within 14 days of treatment initiation)

Serum total bilirubin =< 1.5 upper limit of normal (ULN) or, direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 ULN (performed within 14 days of treatment initiation)

Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 ULN or, =< 5 ULN for participants with liver metastases (performed within 14 days of treatment initiation)

Female participants of childbearing potential are to have a negative serum pregnancy test

Female participants of child-bearing potential must agree to use an acceptable method of birth control, be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after last dose of pembrolizumab and 180 days after the last dose of cetuximab; participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose pembrolizumab and 180 days after the last dose of cetuximab

Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

Participants who have had chemotherapy, targeted therapies, radiotherapy, or used an investigational device within 2 weeks prior to the first dose of treatment or those who have not recovered from adverse events (i.e., =< grade 1 or at baseline) due to agents administered more than 2 weeks earlier; note: participants with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study

Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment

Has a known history of active TB (Bacillus Tuberculosis)

Hypersensitivity to pembrolizumab or any of its excipients

Has a known additional malignancy that requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer

Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability

Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment

Has known history of, or any evidence of active, non-infectious pneumonitis

Uncontrolled clinically significant intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, or psychiatric illness, substance abuse disorders or social situations that would limit compliance with study requirements

Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment

Has a known history of human immunodeficiency virus (HIV or HIV 1/2 antibodies); testing not required

Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected); testing not required

Has received a live vaccine within 30 days of planned start of study therapy (note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and shingles are not allowed)

Received an investigational agent within 30 days prior to starting study treatment

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

Unwilling or unable to follow protocol requirements

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Roswell Park Cancer Institute

  • National Cancer Institute
Patrick McKay Boland, Principal Investigator

Trial Sites

U.S.A.

New York
Buffalo

Roswell Park Cancer Institute

Patrick McKay Boland
Ph: 716-845-3099
Email: Patrick.Boland@RoswellPark.org

Patrick McKay Boland
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT02713373

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.