Efficacy and Safety of Triweekly Cetuximab in Combination With Capecitabine as First-line Maintenance Treatment for KRAS/BRAF Wild-type Metastatic Colorectal Cancer

NCT05775900 | Completed Phase 1

• 1 other identifier: GIHSYSU-29
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

To explore the safety, efficacy and pharmacokinetic (PK) characteristics of triweekly cetuximab in combination with capecitabine as first-line maintenance treatment for KRAS/BRAF wild-type metastatic colorectal cancer: a single-arm, a single-center, Phase 1b trial. Meanwhile, Exploring the maximum tolerant dose or recommended II research dose of triweekly cetuximab combined with a fixed dose of capecitabine using '3+3' dose climbing Phase I experiment.

Conditions

Metastatic Colorectal Cancer

Keywords

First-line Maintenance Therapy; Triweekly Cetuximab; KRAS/BRAF Wild-type

Outcome Measures

Primary Outcomes (3)

• Safety variables (Incidence of Adverse Events [Safety and Tolerability])

  Safety variables will be summarized using descriptive statistics based on adverse events collection

  2 year

• Pharmacokinetic (PK) characteristics 1

  Evaluation Peak Concentration (Cmax) of cetuximab before and after Treatment.

  2 year

• Pharmacokinetic (PK) characteristics 2

  Evaluation Area Under the Curve (AUC0-t, AUC0-∞) of cetuximab before and after Treatment.

  2 year

Secondary Outcomes (5)

• Progression-free survival (PFS)

  2 year

• Overall Survival (OS)

  2 year

• Objective response rate (ORR)

  2 year

• Disease Control Rate (DCR)

  2 year

• Quality of Life (QOL)

  2 year

Other Outcomes (1)

• Treatment-emergent genetic mutations

  2 year

Study Arms (1)

Cetuximab in Combination With Capecitabine

EXPERIMENTAL

Patients were given cetuximab (a '3+3' design was adopted in the experimental arm, with four dose levels of 400mg/m2, 500mg/m2, 600mg/m2 and 700mg/m2 for dose exploration) every 3 weeks (Q3W). Capecitabine, 1000mg/m2, twice a day (BID, once in the morning and once in the evening), 14 days of continuous oral administration followed by 7 days of rest. The two-drug combination therapy was continued every 3 weeks in a cycle until patients developed disease progression or met other criteria for termination of study treatment specified in the protocol.

Drug: Cetuximab; Drug: Capecitabine

Interventions

Cetuximab DRUG

Cetuximab will be given triweekly at a dose from 400mg/m2 to 700mg/m2.

Also known as: Erbitux

Cetuximab in Combination With Capecitabine

Capecitabine DRUG

Capecitabine will be given 2 weeks on/1 week off (1000mg/m2 BID po.)

Also known as: Capecitabine Tablets

Cetuximab in Combination With Capecitabine

Eligibility Criteria

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

You may qualify if:

• Provide a written informed consent form (ICF) before any research procedure is carried out.
• Patients must be ≥18 years old and have an expected life span of at least 12 weeks when signing the ICF.
• Patients have histologically or cytologically confirmed RAS and BRAF wild-type metastatic colorectal adenocarcinoma (mCRC), excluding appendiceal and anal cancers.
• After being diagnosed with mCRC, patients have only received cetuximab combined with chemotherapy (FOLFOX or FOLFIRI) as first-line induction therapy. Imaging progression during adjuvant therapy or within 6 months after completion of adjuvant therapy is considered as first-line treatment.
• Patients have completed 8 cycles of cetuximab combined with chemotherapy induction therapy and the disease is controlled (including CR/PR and SD).
• There is at least one measurable metastatic lesion, defined as per RECIST version 1.1. Patients who have achieved CR without measurable lesions after induction therapy, and those who have achieved no evidence of disease (NED) through R0 resection, interventional ablation, or other local destructive therapies can be included in this study.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Within 7 days before treatment, the following laboratory test values are obtained and appropriate organ function is present:
• Hemoglobin ≥ 90g/L, neutrophil count ≥ 1.5 × 10\^9/L, platelet count ≥ 75 × 10\^9/L; Serum total bilirubin ≤ 1.5 × upper limit of normal (UNL); Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 × UNL; if there are liver metastases, AST or ALT ≤ 5 × UNL; Serum creatinine ≤ 1.5 × UNL.
• Patients are not allowed to participate in other clinical trials during the study period.
• Patients are willing and able to comply with the study protocol and visit plan.

You may not qualify if:

• Excluding adjuvant therapy that ended more than 9 months ago (including oxaliplatin-containing therapy) or more than 6 months ago (excluding oxaliplatin-containing therapy), any chemotherapy for metastatic colorectal cancer (mCRC) other than induction therapy consisting of cetuximab in combination with FOLFOX or FOLFIRI.
• Concurrent active malignancy, excluding malignancies with disease-free survival of 5 years or more or in situ carcinoma considered cured after adequate treatment.
• Known brain metastases or leptomeningeal metastases. Patients with neurological symptoms should undergo brain CT/MRI to exclude metastases.
• Any unresolved toxicities greater than or equal to Grade 2 per the Common Terminology Criteria for Adverse Events (CTCAE) caused by previous treatment, excluding alopecia, skin pigmentation, and anemia. Patients with unresolved neurotoxicity greater than or equal to CTCAE Grade 3 caused by platinum-based drugs should be excluded.
• Ascites, pleural effusion, or pericardial effusion requiring drainage within the past 4 weeks.
• Patients with bowel obstruction, gastrointestinal bleeding, pulmonary fibrosis or interstitial pneumonia, renal failure, liver failure, or cerebrovascular disease.
• Uncontrolled diabetes, defined as HbA1c \>7.5% after the use of antidiabetic drugs, or uncontrolled hypertension, defined as systolic/diastolic blood pressure \>140/90mmHg after the use of antihypertensive drugs.
• Myocardial infarction within the past 12 months, severe/unstable angina pectoris, or New York Heart Association (NYHA) Class III or IV congestive heart failure symptoms.
• A history of allergy to any study drugs (such as cetuximab or capecitabine).
• Known infection with human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS) related diseases, hepatitis B or C.
• Autoimmune diseases or a history of organ transplantation requiring immunosuppressive therapy.
• Mental illness that may increase the risk associated with participation in the study or interfere with the interpretation of study results.
• Received any of the following treatments within a specified time period prior to receiving the study drug:
• Major surgery within 4 weeks (excluding diagnostic biopsy, surgical incision should be completely healed before administering the study drug).
• Radiotherapy within 4 weeks. Other anti-tumor treatments or participation in other clinical trials within 4 weeks, except for induction therapy as specified in the protocol.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510655, 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

• Yanhong Deng, Ph.D

  Sixth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Medical Oncology, Clinical Professor

Study Record Dates

• First Submitted: February 25, 2023
• First Posted: March 20, 2023
• Study Start: February 1, 2023
• Primary Completion: July 31, 2025
• Study Completion: August 26, 2025
• Last Updated: September 3, 2025

Record last verified: 2025-07

Locations

CN (1)