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

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Enrolling; Phase 3

Conditions: Colo-rectal Cancer

Treatments: Drug: Experimental: mXELOX plus cetuximab; Drug: Active Comparator: FOLFOX plus cetuximab

Study type: Interventional

Funder types: Other

Identifiers

NCT05074966

mCRC-CLARIFY-2021

Details and patient eligibility

About

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.

Enrollment: 314 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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
• May increase the risk associated with participation in the study or administration of the study drug or mental illness that may interfere with the interpretation of research results
• Pregnant women (determined by serum human chorionic gonadotropin [hCG]) or lactating women, or plan to conceive during the treatment period, 2 months after cetuximab treatment and 6 months after capecitabine treatment. Women of childbearing age with positive or no pregnancy test at baseline. Women of childbearing age or sexually active men were not willing to use contraception during the study period, at least 2 months after cetuximab treatment and 6 months after capecitabine treatment. Postmenopausal women must be amenorrhea for at least 12 months to be considered infertile
• There are other serious diseases that the researchers believe patients cannot be included in the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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314 participants in 2 patient groups

mXELOX plus cetuximab

Experimental group

Description:

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;

Treatment:

Drug: Experimental: mXELOX plus cetuximab

FOLFOX plus cetuximab

Active Comparator group

Description:

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）

Treatment:

Drug: Active Comparator: FOLFOX plus cetuximab