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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT05775900
Recruitment Status : Recruiting
First Posted : March 20, 2023
Last Update Posted : March 20, 2023
Information provided by (Responsible Party):
Yanhong Deng, Sun Yat-sen University

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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: Cetuximab Drug: Capecitabine Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Triweekly Cetuximab in Combination With Capecitabine as First-line Maintenance Treatment for KRAS/BRAF Wild-type Metastatic Colorectal Cancer
Actual Study Start Date : February 1, 2023
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : June 30, 2024

Resource links provided by the National Library of Medicine

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 Name: Erbitux

Drug: Capecitabine
Capecitabine will be given 2 weeks on/1 week off (1000mg/m2 BID po.)
Other Name: Capecitabine Tablets

Primary Outcome Measures :
  1. 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. Pharmacokinetic (PK) characteristics 1 [ Time Frame: 2 year ]
    Evaluation Peak Concentration (Cmax) of cetuximab before and after Treatment.

  3. Pharmacokinetic (PK) characteristics 2 [ Time Frame: 2 year ]
    Evaluation Area Under the Curve (AUC0-t, AUC0-∞) of cetuximab before and after Treatment.

Secondary Outcome Measures :
  1. 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. 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.

  3. 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).

  4. 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)

  5. 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.

Other Outcome Measures:
  1. Treatment-emergent genetic mutations [ Time Frame: 2 year ]
    Assessment of the correlation between mutation status of relevant genes and treatment response through ctDNA testing.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT05775900

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Contact: Yanhong Deng, Ph.D 86-13925106525
Contact: Xiaoyu Xie, M.D. 86-13570487315

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China, Guangdong
The Sixth Affiliated Hospital of Sun Yat-sen University Recruiting
Guangzhou, Guangdong, China, 510655
Contact: Yanhong Deng, M.D.    86-13925106525   
Sponsors and Collaborators
Sun Yat-sen University
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Principal Investigator: Yanhong Deng, Ph.D Sixth Affiliated Hospital, Sun Yat-sen University
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Responsible Party: Yanhong Deng, Director of Medical Oncology, Clinical Professor, Sun Yat-sen University Identifier: NCT05775900    
Other Study ID Numbers: GIHSYSU-29
First Posted: March 20, 2023    Key Record Dates
Last Update Posted: March 20, 2023
Last Verified: March 2023

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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
Keywords provided by Yanhong Deng, Sun Yat-sen University:
First-line Maintenance Therapy
Triweekly Cetuximab
KRAS/BRAF Wild-type
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Immunological