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

NCT02713373 | Completed Phase 1 Results DMC

• 3 other identifiers: I 274515NCI-2016-00228P30CA016056
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

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.

Conditions

Recurrent Colorectal Carcinoma; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

Outcome Measures

Primary Outcomes (3)

• To Examine the Adverse Event Profile

  The frequency of toxicities will be tabulated by maximum grade by preferred term within a patient across all cycles.

  up to 24 months

• Progression Free Survival (PFS), Evaluated According to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

  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.

  At 6 months

• Number of Participants With a Response, Evaluated According to RECIST 1.1

  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.

  Up to 2 years

Secondary Outcomes (3)

• 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

Study Arms (1)

Arm I (cetuximab and pembrolizumab)

EXPERIMENTAL

Patients receive cetuximab IV over 120 minutes on day 1 (days 1, 7, and 14 of course 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.

Biological: Cetuximab; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

Cetuximab BIOLOGICAL

Given IV

Also known as: Chimeric Anti-Epidermal Growth Factor Receptor (EGFR) Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225, Erbitux, IMC-C225

Arm I (cetuximab and pembrolizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (cetuximab and pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Arm I (cetuximab and pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• Hemoglobin \>= 8 g/dL (performed within 14 days of treatment initiation)
• Absolute neutrophil count \>= 1000/mm3 (performed within 14 days of treatment initiation)
• Platelet count \>= 100,000/mm3 (performed within 14 days of treatment initiation)
• Serum creatinine =\< 2 upper limit of normal (ULN) or, \>= 15 mL/min for participants with creatinine levels \> 2 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• National Cancer Institute (NCI): collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

University Hospitals Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Antibodies, Monoclonal; pembrolizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Katy Wang
• Organization: Roswell Park Comprehensive Cancer Center

Chong.Wang@RoswellPark.org

716-845-1300

Study Officials

• Christos Fountzilas

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2016
• First Posted: March 18, 2016
• Study Start: August 5, 2016
• Primary Completion: July 28, 2020
• Study Completion: July 20, 2021
• Last Updated: October 6, 2022
• Results First Posted: December 3, 2021

Record last verified: 2022-09

Locations

US (2)