A Phase Ib/II Study of Cetuximab and Pembrolizumab in Metastatic Colorectal Cancer
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Recurrent Colorectal Carcinoma
- Sponsor
- Roswell Park Cancer Institute
- Enrollment
- 45
- Locations
- 2
- Primary Endpoint
- To Examine the Adverse Event Profile
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief 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.
Detailed Description
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. EXPLORATORY 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, 8, and 15 (as monotherapy for cycle 1 only) and 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.
Investigators
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
- •Retrovirus-associated deoxyribonucleic acid (DNA) sequence (RAS) wild-type; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) testing must be completed, with full KRAS and neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) testing strongly advised; the presence of known mutations in KRAS or NRAS is exclusionary; primary tumor or metastatic tumor may be tested; (note: in the case of multiple genomic evaluations with conflicting results - e.g. KRAS mutant in one sample, but wild-type in another - the patient may be included as RAS wild-type, if clinically justified, after review with the principal investigator \[PI\])
- •Appropriate for anti-EGFR therapy: Naive to anti-EGFR therapy (cetuximab or panitumumab) or a candidate for rechallenge by virtue of the following:
- •the investigator deems anti-EGFR retreatment with cetuximab to be a reasonable standard of care option AND
- •outcome of prior anti-EGFR therapy was not rapid progression (i.e. \<= 3 months on therapy) AND
- •prior anti-EGFR therapy was administered \> 6 months prior to the start of protocol therapy
- •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
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
- •Prior severe infusion reaction to cetuximab
- •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
Outcomes
Primary Outcomes
To Examine the Adverse Event Profile
Time Frame: up to 24 months
The frequency of toxicities will be tabulated by maximum grade by preferred term within a patient across all cycles.
Progression Free Survival (PFS), Evaluated According to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
Time Frame: At 6 months
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), At least a 20% increase in the sum of diameters of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Number of Participants With a Response, Evaluated According to RECIST 1.1
Time Frame: Up to 2 years
Number of Participants with a Response, Evaluated According to RECIST 1.1 will be tabulated and will be compared to the null values using exact tests.
Secondary Outcomes
- Objective Tumor Response Using Immune-related RECIST(up to 24 months)
- Overall Survival (OS)(Up to death, withdrawal of consent, or the end of the study, whichever occurs first, assessed up to 2 years)
- Progression Free Survival (PFS)(Up to15 months)