Cetuximab in Third Line for Mutant APC, TP53 and RAS Patients With Refractory Metastatic Colorectal Cancer

NCT04853043 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: HCI141689R21CA252436
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

A prospective, multi-center, phase II study of 21 patients to evaluate the efficacy of the epidermal growth factor receptor (EGFR) inhibitor, Cetuximab in patients with metastatic colorectal cancer (mCRC) harboring Adenomatous polyposis coli (APC), tumor protein p53 (TP53) and RAS mutations.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Evaluate the PFS among patients treated with cetuximab in APC, TP53 and RAS mutated refractory metastatic colorectal cancer. PFS will be measured from the date of first dose of study drug until the first documented radiographic evidence of disease progression by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) criteria 1.1, clinical progression per investigator judgement, start of new anti-cancer therapy, or death from any cause. Per RECIST 1.1 for target lesions, Progressive Disease (PD) is a \>=20% increase in the sum of the longest diameter (LD) of target lesions. Disease progression by RECIST 1.1 is PD.

  PFS will be measured from the date of first dose of study drug until first documented clinical or radiographic evidence of disease progression by RECIST 1.1, clinical progression, start of new therapy or death. Estimated assessment at 6 months.

Secondary Outcomes (1)

• Overall Survival (OS).

  OS was measured from the date of first dose of study drug until death from any cause (up to 223 days)

Study Arms (1)

Cetuximab

EXPERIMENTAL

Drug: Cetuximab

Interventions

Cetuximab DRUG

Cetuximab will be administered every 2 weeks (14 days). The initial dose of 500 mg/m2 is to be administered by IV infusion over 120 minutes on the first day of the treatment. In the absence of infusion reactions, subsequent doses are to be administered over 60 minutes biweekly. Each cycle will be defined as 14 days of treatment.

Cetuximab

Eligibility Criteria

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

You may qualify if:

• Male or female subject aged ≥ 18 years.
• Histologically confirmed metastatic colorectal adenocarcinoma with mutant APC, TP53 and KRAS genes as determined by the local Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory are eligible. All RAS mutations are allowed (KRAS, Neuroblastoma RAS (NRAS), HRAS). Patients with wild type KRAS, APC or TP53 are ineligible.
• Progression or unwanted toxicities on at least 2 prior lines of treatment including 5-Fluorouracil, oxaliplatin and irinotecan-based regimen
• Study participants must have measurable disease by RECIST 1.1 criteria by CT or MRI.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
• Study participants with treated and/or stable brain metastases are allowed
• Study participants must have anticipated life expectancy \> 3 months
• Adequate organ function as defined as:
• Hematologic:
• Absolute neutrophil count (ANC) ≥ ≥1000/µL
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 9 g/dL
• Hepatic:
• Serum Bilirubin ≤ 2 x ULN or ≤ 3 x ULN for subjects with Gilbert's syndrome
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 times the upper limit of normal (ULN; or 5.0 times the ULN in the setting of liver metastases)

You may not qualify if:

• Prior use of systemic anti-EGFR therapy including cetuximab or panitumumab is not allowed but prior use irinotecan, oxaliplatin, regorafenib or Trifluridine/Tipiracil (TAS-102) is allowed
• Study participants with prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of the investigational regimen, as determined by the investigator
• Study participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease who need immediate central nervous system (CNS)-specific treatment during first cycle of treatment as determined by the treating physician.
• Note: Brain metastases or cranial epidural disease adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before the first dose of study treatment will be allowed on trial. Subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the first dose of study treatment.
• Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
• The patient has clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months or high risk of uncontrolled arrhythmia or uncontrolled cardiac insufficiency.
• The patient has uncontrolled or poorly-controlled hypertension (\>180 mmHg systolic or \> 130 mmHg diastolic.
• Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, \[subjects may not receive the drug through a feeding tube\], social/ psychological issues, etc.)
• Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment.
• Note: Subjects on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial.
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and tuberculosis (TB) testing in line with local practice), hepatitis B (known positive hepatitis B virus (HBV) surface antigen (HBsAg) result), or hepatitis C.
• Note: Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody (anti-HBc) and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study.
• Known prior severe hypersensitivity attributed to compounds of chemical or biologic composition similar to those of cetuximab, or if the patient had red meat allergy/tick bite history (NCI CTCAE v5.0 Grade ≥ 3).
• Live attenuated and inactive vaccinations within 4 weeks of the first dose of study treatment and while on trial is prohibited. Coronavirus Disease 19 (COVID-19) vaccines are allowed

Sponsors & Collaborators

• University of Utah: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Intermountain Medical Center

Salt Lake City, Utah, 84107, United States

Location

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab

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

Results Point of Contact

• Title: IIT Data Management Team
• Organization: Research Compliance Office, Huntsman Cancer Institute

IITDataManagement@hci.utah.edu

801-213-6215

Study Officials

• Vaia Florou, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm, open label

Study Record Dates

• First Submitted: April 16, 2021
• First Posted: April 21, 2021
• Study Start: November 3, 2021
• Primary Completion: February 20, 2024
• Study Completion: May 3, 2024
• Last Updated: May 6, 2025
• Results First Posted: May 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)