The Efficacy and Safety of Modified XELOX(mXELOX) Plus Cetuximab vs FOLFOX Plus Cetuximab in RAS and BRAF WT mCRC Pts

NCT05074966 | Unknown Phase 3

• 1 other identifier: mCRC-CLARIFY-2021
• Study Type: interventional
• Target: 314
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, multicenter, randomized study in Chinese patients with RAS and BRAF wild-type mCRC. Participants were randomly assigned to cetuximab + FOLFOX (group A) and cetuximab + modified XELOX\[mXELOX\] (group B). All patients in groups A and B will be treated until progression of disease(PD), death, intolerable toxicity or withdrawal of informed consent, whichever occurs first.

Conditions

Colo-rectal Cancer

Outcome Measures

Primary Outcomes (1)

• median PFS

  from randomization to PD or death from any cause

  From Baseline to primary completion date, about 48 months

Secondary Outcomes (8)

• Number of Participants With Adverse Events（AEs） During Treatment Period

  From Baseline to primary completion date, about 48 months

• Number of Participants With Hematology Abnormalities During Treatment Period

  From Baseline to primary completion date, about 48 months

• Number of Participants With Electrolyte Abnormalities During Treatment Period

  From Baseline to primary completion date, about 48 months

• Number of Participants With Clinical chemistry Abnormalities During Treatment Period

  From Baseline to primary completion date, about 48 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 48 months

Study Arms (2)

mXELOX plus cetuximab

EXPERIMENTAL

Patients will receive the study drug after randomization, and those with effective efficacy evaluation (CR, PR or SD) will receive intravenous chemotherapy for up to 9 cycles, and then enter the maintenance treatment stage until PD, death, intolerable toxicity or withdrawal of informed consent (whichever occurs first) Cetuximab: 500 mg/m2, IV, d1, q2w; Oxaliplatin: 85 mg/m2, IV, d1,q2w; Capecitabine: 850 mg/m2, po, bid, d1-10, q2w; maintenance stage: Cetuximab: 500 mg/m2, IV, d1, q2w; Capecitabine: 850 mg/m2, po, bid, d1-10, q2w;

Drug: Experimental: mXELOX plus cetuximab

FOLFOX plus cetuximab

ACTIVE COMPARATOR

Patients will receive the study drug after randomization, and those with effective efficacy evaluation (CR, PR or SD) will receive intravenous chemotherapy for up to 9 cycles, and then enter the maintenance treatment stage until PD, death, intolerable toxicity or withdrawal of informed consent (whichever occurs first) Cetuximab：500 mg/m2, IV, d1, q2w Oxaliplatin： 85 mg/m2, IV d1, q2w; Leucovorin： 400 mg/m2 IV d1, q2w; 5-FU： 400 mg/m2 IV bolus on d1, then 1200 mg/m2/d x 2d(total 2400 mg/m2 over 46-48 hours) IV continuous infusion, q2w; maintenance stage: Cetuximab: 500 mg/m2, IV, d1, q2w; Leucovorin： 400 mg/m2 IV d1, q2w; 5-FU： 400 mg/m2 IV bolus on d1, then 1200 mg/m2/d x 2d(total 2400 mg/m2 over 46-48 hours) IV continuous infusion, q2w （Cetuximab combined with capecitabine can be used according to the patient's wishes and the nursing situation of intravenous catheterization）

Drug: Active Comparator: FOLFOX plus cetuximab

Interventions

Experimental: mXELOX plus cetuximab DRUG

Patients will receive the study drug after randomization, and those with effective efficacy evaluation (CR, PR or SD) will receive intravenous chemotherapy for up to 9 cycles, and then enter the maintenance treatment stage until PD, death, intolerable toxicity or withdrawal of informed consent (whichever occurs first) Cetuximab: 500 mg/m2, IV, d1, q2w; Oxaliplatin: 85 mg/m2, IV, d1,q2w; Capecitabine: 850 mg/m2, po, bid, q2w maintenance stage: Cetuximab: 500 mg/m2, IV, d1, q2w; Capecitabine: 850 mg/m2, po, bid, d1-10, q2w;

mXELOX plus cetuximab

Active Comparator: FOLFOX plus cetuximab DRUG

Patients will receive the study drug after randomization, and those with effective efficacy evaluation (CR, PR or SD) will receive intravenous chemotherapy for up to 9 cycles, and then enter the maintenance treatment stage until PD, death, intolerable toxicity or withdrawal of informed consent (whichever occurs first) Oxaliplatin 85 mg/m2, IV d1; Leucovorin 400 mg/m2 IV d1; 5-FU 400 mg/m2 IV bolus on d1, then 1200 mg/m2/d x 2d(total 2400 mg/m2 over 46-48 hours) IV continuous infusion; q2w maintenance stage: Cetuximab: 500 mg/m2, IV, d1, q2w; Leucovorin： 400 mg/m2 IV d1, q2w; 5-FU： 400 mg/m2 IV bolus on d1, then 1200 mg/m2/d x 2d(total 2400 mg/m2 over 46-48hours) IV continuous infusion, q2w （Cetuximab combined with capecitabine can be used according to the patient's wishes and the nursing situation of intravenous catheterization）

FOLFOX plus cetuximab

Eligibility Criteria

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

You may qualify if:

• Provide written informed consent (ICF) prior to any study procedure.
• Patient must be ≥18 years of age, at the time of signing the informed consent.
• Patients who had histologically or cytologically confirmed RAS and BRAF wild-type, initially unresectable metastatic adenocarcinoma of the left-sided colon or rectum, excluding appendiceal or anal cancer.
• The patients were willing to receive FOLFOX /mXELOX plus cetuximab as the first-line treatment choice after the diagnosis of mCRC;
• At least one measurable metastatic lesion(s) as defined by RECIST version 1.1. Eastern Cooperative Oncology Group (ECOG) performance score was 0-1 or KPS score ≥ 80.
• Life expectancy of at least 12 weeks in the opinion of the investigator.
• Neutrophils ≥ 1.5 × 109 / L, platelet ≥ 75 × 109 / L and hemoglobin ≥ 9 g / dl; Total bilirubin ≤ 1.5 × upper limit of normal value (ULN); ASAT (SGOT) and / or ALAT (SGPT) ≤ 2.5 × UNL (≤5×ULN in case of liver metastases）； Alkaline phosphatase ≤ 2.5 × UNL (≤ 5 × ULN in case of liver metastases; ≤ 10× ULN in case of bone metastasis ）； 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:

• Previously received chemotherapy for CRC, except for adjuvant therapy\>9 months (chemotherapy with oxaliplatin) or \>6 months (chemotherapy without oxaliplatin) before the start of the study
• Patients that has been treated with monoclonal antibody, VEGF pathway targeted therapy, EGFR pathway targeted therapy, or other signal transduction pathway inhibitors
• Radiotherapy, RFA, interventional therapy or surgery were performed within 28 days before the first medication (except for previous diagnostic biopsy)
• Other active malignant tumors, excluding those who have been disease free for more than 5 years or in situ cancer considered to have been cured by adequate treatment
• Brain metastasis or meningeal metastasis has been confirmed. Patients with neurological symptoms should receive brain CT / MRI examination to exclude metastasis
• Peripheral nerve disorder is above grade 1(NCI CTCAE Version 5 )
• Existing toxicity or unrecovered toxicity caused by previous treatment whose grade is above 2 according to CTCAE criteria(excluding anemia, alopecia, skin pigmentation)
• Ascites, pleural effusion or pericardial fluid requiring drainage in the past 4 weeks
• Patients who is suffering from intestinal obstruction, gastrointestinal bleeding, pulmonary fibrosis or interstitial pneumonia, renal failure, liver failure or cerebrovascular disease
• Diabetes was not controlled, defined as HbA1c \> 7.5% after anti-diabetic drugs or hypertension was not controlled, defined as systolic / diastolic blood pressure \> 140 / 90 mmHg after antihypertensive drug
• Myocardial infarction, severe/unstable angina, New York Heart Association (NYHA) class III or IV congestive heart failure in the past 12 months
• Patients who was allergic to any of the research drugs (cetuximab, 5-FU, oxaliplatin, capecitabine) in the past
• Deficiency in dihydropyrimidine dehydrogenase (DPD) as manifested by medical history of fluorouracil adverse reactions
• Known to be infected with human immunodeficiency virus (HIV), have acquired immunodeficiency syndrome (AIDS) related diseases, have active hepatitis B or hepatitis C
• Suffering from autoimmune diseases or history of organ transplantation requiring immunosuppressive therapy

Sponsors & Collaborators

• Chinese Academy of Medical Sciences: lead

Study Sites (1)

Cancer Hospital & Institute, Chinese Academy of Medical Sciences

Beijing, 100021, China

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Aiping Zhou, Doctor

  Cancer Hospital & Institute, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aiping Zhou, Doctor

CONTACT

8610-87788145; ZHOUAP1825@126.COM

Yongkun Sun, Doctor

CONTACT

8610-87788145; hsunyk@126.com

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: Deputy director of Internal Medicine

Model Details: patients with RAS/BRAF wild type left-sided mCRC will be randomized to two groups, which are mXELOX plus cetuximab and FOLFOX plus cetuximab.

Study Record Dates

• First Submitted: September 7, 2021
• First Posted: October 12, 2021
• Study Start: September 6, 2021
• Primary Completion: June 24, 2024
• Study Completion: June 24, 2025
• Last Updated: October 12, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)