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

March 19, 2024 updated by: Yanhong Deng, Sun Yat-sen University
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Xiaoyu Xie, M.D.
  • Phone Number: 86-13570487315
  • Email: xie_xyu@163.com

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510655
        • Recruiting
        • The Sixth Affiliated Hospital of Sun Yat-sen University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

  • Pregnant (confirmed by serum human chorionic gonadotropin [hCG] test) or lactating women, or women of childbearing potential who plan to become pregnant during the treatment period and within 2 months after the end of cetuximab treatment, or within 6 months after the end of capecitabine treatment. Women of childbearing potential or sexually active men who are unwilling to use contraception during the study period and for at least 2 months after the end of cetuximab treatment, or 6 months after the end of capecitabine treatment. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.
  • Presence of any other serious illness that, in the investigator's opinion, would preclude the patient's participation in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cetuximab in Combination With Capecitabine

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
Cetuximab will be given triweekly at a dose from 400mg/m2 to 700mg/m2.
Other Names:
  • Erbitux
Drug: Capecitabine
Capecitabine will be given 2 weeks on/1 week off (1000mg/m2 BID po.)
Other Names:
  • Capecitabine Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety variables (Incidence of Adverse Events [Safety and Tolerability])
Time Frame: 2 year
Safety variables will be summarized using descriptive statistics based on adverse events collection
2 year
Pharmacokinetic (PK) characteristics 1
Time Frame: 2 year
Evaluation Peak Concentration (Cmax) of cetuximab before and after Treatment.
2 year
Pharmacokinetic (PK) characteristics 2
Time Frame: 2 year
Evaluation Area Under the Curve (AUC0-t, AUC0-∞) of cetuximab before and after Treatment.
2 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: 2 year
OS is defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
2 year
Disease Control Rate (DCR)
Time Frame: 2 year
DCR is defined as the percentage of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating)
2 year
Progression-free survival (PFS)
Time Frame: 2 year
The PFS is defined as the time from the start of treatment to the date of first documented PD or death as a result of any cause, whichever occurred first. When a patient was alive and without progression, PFS was censored at the date of the last disease assessment.
2 year
Objective response rate (ORR)
Time Frame: 2 year
The percentage of subjects with total number of Complete Response (CR) + total number of Partial Response (PR).
2 year
Quality of Life (QOL)
Time Frame: 2 year
Evaluation of alterations in patients' quality of life throughout treatment by using the EORTC QLQ-CR29 and EORTC QLQ-CR30 quality of life questionnaire. Evaluation of the scores was based on the Karnofsky Performance Scale (KPS). The reliability and validity of the questionnaires were assessed by Cronbach's α coefficient, the Spearman correlation test and Wilcoxon rank sum test.
2 year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment-emergent genetic mutations
Time Frame: 2 year
Assessment of the correlation between mutation status of relevant genes and treatment response through ctDNA testing.
2 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Investigators

  • Principal Investigator: Yanhong Deng, Ph.D, Sixth Affiliated Hospital, Sun Yat-sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2023

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

February 25, 2023

First Submitted That Met QC Criteria

March 7, 2023

First Posted (Actual)

March 20, 2023

Study Record Updates

Last Update Posted (Actual)

March 21, 2024

Last Update Submitted That Met QC Criteria

March 19, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GIHSYSU-29

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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