Clinical trial NCT05074966: The Efficacy and Safety of Modified XELOX(mXELOX) Plus Cetuximab vs FOLFOX Plus Cetuximab in RAS and BRAF WT mCRC Pts
Official title: A Phase III, Multicenter, Open-label, Randomized Study to Assess the Efficacy and Safety of mXELOX Plus Cetuximab Versus FOLFOX Plus Cetuximab in Chinese Patients With RAS and BRAF Wild-type Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Colo-rectal Cancer
Lead sponsor: ChineseAMS
Sponsor class: UNKNOWN
First posted: 2021-10-12
Enrollment: 314
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: patients with RAS/BRAF wild type left-sided mCRC will be randomized to two groups, which are mXELOX plus cetuximab and FOLFOX plus cetuximab.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: median PFS
timeFrame: From Baseline to primary completion date, about 48 months
Secondary outcomes:
measure: Number of Participants With Adverse Events（AEs） During Treatment Period
timeFrame: From Baseline to primary completion date, about 48 months
measure: Number of Participants With Hematology Abnormalities During Treatment Period
timeFrame: From Baseline to primary completion date, about 48 months
measure: Number of Participants With Electrolyte Abnormalities During Treatment Period
timeFrame: From Baseline to primary completion date, about 48 months
measure: Number of Participants With Clinical chemistry Abnormalities During Treatment Period
timeFrame: From Baseline to primary completion date, about 48 months
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CR29 (EORTC QLQ-CR29)
timeFrame: From Baseline to primary completion date, about 48 months
measure: Change From Baseline in 5-level EuroQol-5 Dimensions(EQ-5D-5L)
timeFrame: From Baseline to primary completion date, about 48 months
measure: objective response rate
timeFrame: From Baseline to primary completion date, about 48 months.
measure: Overall Survival OS
timeFrame: From Baseline to primary completion date, about 48 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital & Institute, Chinese Academy of Medical Sciences
Study officials:
affiliation: Cancer Hospital & Institute, Chinese Academy of Medical Sciences
name: Aiping Zhou, Doctor
role: PRINCIPAL_INVESTIGATOR
References: