Cetuximab Plus Capecitabine as Maintenance Treatment in RAS and BRAF wt Metastatic Colorectal Cancer

NCT04262635 | Unknown Phase 3

• 1 other identifier: C-CLASSIC
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, multicenter, randomized study to be conducted in Chinese patients with RAS and BRAF wild-type mCRC. Patients who have already completed 9 cycles of standard first-line induction treatment, without discontinuation for toxicity, of cetuximab or fluorouracil or oxaliplatin,, and achieved disease control (including CR/PR and SD), and are progression free at the end of Cycle 9 will be assigned to 2 maintenance treatment groups by randomization in a 1:1 ratio to receive cetuximab + capecitabine (Arm A) or cetuximab alone (Arm B). The randomization will be stratified by induction treatment response (complete response \[CR\]+ partial response \[PR\] versus stable disease \[SD\]) and primary tumor location (left side only versus right side). All patients from Arm A and Arm B will be treated until progressive disease, death from any cause, unacceptable toxicity or informed consent withdrawal (whichever occurs earlier).

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Efficacy: Maintenance PFS

  mPFS from randomization to PD or death from any cause

  From Baseline to primary completion date, about 42 months

Secondary Outcomes (5)

• Number of Participants With Adverse Events During Treatment Period

  From Baseline to primary completion date, about 42 months

• Number of Participants With Clinical Laboratory Abnormalities During Treatment Period

  From Baseline to primary completion date, about 42 months

• Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)

  From Baseline to primary completion date, about 42 months

• Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CR29 (EORTC QLQ-CR29)

  From Baseline to primary completion date, about 42 months

• Overall Survival

  From Baseline to primary completion date, about 42 months

Other Outcomes (1)

• Change from Baseline in Mutation Status of Selected Genes tested by Next-Generation Sequencing during Treatment Period

  From Baseline to primary completion date, about 42 months

Study Arms (2)

ArmA Cetuximab plus Capecitabine

EXPERIMENTAL

Maintenance therapy with Cetuximab as intravenous (IV) infusion at the dose of 500 mg/m2, given every 2 weeks (Q2W); plus capecitabine in 2-week cycles until progressive disease, death from any cause, unacceptable toxicity or informed consent withdrawal

Drug: Cetuximab, Capecitabine

ArmB Cetuximab

ACTIVE COMPARATOR

Maintenance therapy with Cetuximab as intravenous (IV) infusion at the dose of 500 mg/m2, given every 2 weeks (Q2W) until progressive disease, death from any cause, unacceptable toxicity or informed consent withdrawal

Drug: Cetuximab

Interventions

Cetuximab, Capecitabine DRUG

Maintenance treatment ( ArmA )

ArmA Cetuximab plus Capecitabine

Cetuximab DRUG

Maintenance treatment ( ArmB )

ArmB Cetuximab

Eligibility Criteria

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

You may qualify if:

• Written informed consent prior to performance of any study procedure.
• Patient must be ≥18 years of age, at the time of signing the informed consent.
• Patients who have histologically or cytologically confirmed adenocarcinoma of the colon or rectum, excluding appendix carcinoma or anal canal carcinoma, with RAS and BRAF wild-type mutation status.
• Patients who received only FOLFOX plus cetuximab as first-line induction treatment after diagnosis of mCRC.
• Having completed FOLFOX plus cetuximab for 9 cycles as induction treatment (in the first cycle, they could be treated with FOLFOX alone for waiting the results of genetic test) without discontinuation for toxicity, of cetuximab or fluorouracil or oxaliplatin and achieved disease control (including CR/PR and SD) and are progression free at the start of maintenance therapy.
• At least one lesion(s), which is considered as unresectable at start of maintenance therapy (mCRC patients with resectable lesion(s) after induction treatment can be enrolled if they are willing to choose maintenance therapy). Patients who achieved CR and had no measurable lesion after induction treatment can be enrolled in this study.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Life expectancy of at least 12 weeks in the opinion of the investigator.
• Laboratory requirements
• Neutrophils ≥1.5×109/L, platelets ≥75×109/L, and hemoglobin ≥9 g/dL;
• Total bilirubin ≤1.5×upper limit of normal (ULN); aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT)
• ×ULN (≤5×ULN in case of liver metastases); alkaline phosphatase
• ×ULN (≤5×ULN in case of liver metastases, ≤10×ULN in case of bone metastases); lactate dehydrogenase (LDH) \<1500 U/L;
• Creatinine clearance (calculated according to Cockcroft and Gault) \>60 mL/min or serum creatinine ≤1.5×ULN.

You may not qualify if:

• Having received chemotherapy for mCRC other than induction therapy with FOLFOX plus cetuximab, except for adjuvant therapy that has ended \>9 months (oxaliplatin- based chemotherapy) or \>6 months (oxaliplatin-free chemotherapy), prior to the start of the induction treatment.
• Other concurrently active malignancies, excluding malignancies that are disease free for more than 5 years or carcinoma-in-situ deemed cured by adequate treatment. Patients who are definitely detected as dMMR/MSI-H at the start of induction therapy.
• Known brain metastasis or leptomeningeal metastasis. Patients with neurological symptoms should undergo brain computed tomography (CT)/ magnetic resonance imaging (MRI) to exclude metastases.
• Unresolved toxicity greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation). Patients with platinum induced neurotoxicity greater than or equal to CTCAE Grade 3 should be excluded.
• Ascites, pleural effusion or pericardial fluid requiring drainage in last 4 weeks.
• Intestinal obstruction, major gastrointestinal hemorrhage or other diseases not suitable for maintenance treatment in this study as assessed by the investigator within 2 weeks prior to enrollment.
• Diabetes and hypertension as assessed by the investigator as not eligible for the subsequent maintenance treatment in this study.
• Myocardial infarction within the last 12 months, severe/unstable angina, symptoms of class III or IV congestive heart failure per New York Heart Association (NYHA) classification.
• Previous hypersensitivity to any of the study drugs (cetuximab or capecitabine).
• Deficiency in dihydropyrimidine dehydrogenase (DPD) as manifested by known medical history of fluorouracil adverse reactions.
• Known infection with human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS)-related illness, or active hepatitis B (positive HBsAg and HBV-DNA ≥ 2000 IU/mL or 104 copies/mL) or hepatitis C. Patients with previously confirmed COVID-19 infection, including severe, mild, asymptomatic, and recovered patients.
• Patients with active autoimmune disorders requiring treatment or history of organ transplantation requiring immunosuppressive therapy.
• Psychiatric disease that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results.
• Treatment with any of the following within the specified time frame prior to study drug administration
• Major surgery within 4 weeks (excluding diagnostic biopsy, the surgical incision should be fully healed prior to study drug administration);

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Capecitabine

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; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Ruihua Xu, MD

  Sun Yat-sen University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 5, 2020
• First Posted: February 10, 2020
• Study Start: September 24, 2021
• Primary Completion: December 31, 2022
• Study Completion: August 30, 2024
• Last Updated: August 2, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)