mFOLFOXIRI+Bev vs. mFOLFOX6+Bev for RAS Mutant Unresectable Colorectal Liver-limited Metastases

NCT04781270 | Recruiting Phase 3

• 1 other identifier: BECOME2
• Study Type: interventional
• Target: 308
• Locations: 1 country
• Sites: 1

Brief Summary

Colorectal cancer patients with initially unresectable liver-only metastases may be cured after downsizing of metastases by conversion therapy. However, the optimal regimen of conversion therapy for RAS mutant patients has not been defined. In this study colorectal cancer patients with initially unresectable liver-only metastases, as prospectively confirmed by a local multidisciplinary team (MDT) according to predefined criteria, will be tested for RAS and BRAF tumor mutation status. Patients with RAS mutant and BRAF wild type will be randomised between modified FOLFOXIRI (mFOLFOXIRI) plus bevacizumab and modified FOLFOX6 (mFOLFOX6) plus bevacizumab. Patient imaging will be reviewed for resectability by MDT, consisting of at least one radiologist and three liver surgeons every assessment. MDT review will be performed prior to randomization as well as during treatment, as described in the protocol.

Conditions

Colorectal Carcinoma; Liver Metastases

Outcome Measures

Primary Outcomes (1)

• conversion resection rate

  R0 resection rate upon conversion treatment with chemotherapy plus bevacizumab

  up to 6 months

Secondary Outcomes (8)

• Overall survival (OS)

  up to 2 years

• Progression-free survival (PFS)

  up to 2 years

• Toxicity (AE)

  up to 6 months

• postoperative complication

  After surgery during one month

• overall response

  up to 6 months

Study Arms (2)

mFOLFOXIRI+Bev

EXPERIMENTAL

Patients will receive mFOLFOXIRI plus bevacizumab once every two weeks as the first-line treatment. Drug: mFOLFOXIRI plus Bevacizumab Bevacizumab (5 mg/kg on day 1) plus mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 165 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1). A local MDT will assess the efficiency every 4 cycles of the treatment. The maximum period of conversion therapy is 12 cycles.

Drug: mFOLFOXIRI regimen; Drug: Bevacizumab

mFOLFOX6+Bev

ACTIVE COMPARATOR

Patients will receive mFOLFOX6 plus bevacizumab once every two weeks as the first-line treatment. Drug: mFOLFOX6 Plus Bevacizumab mFOLFOX6 (oxaliplatin 85 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1). A local MDT will assess the efficiency every 4 cycles of the treatment. The maximum period of conversion therapy is 12 cycles.

Drug: mFOLFOX regimen; Drug: Bevacizumab

Interventions

mFOLFOXIRI regimen DRUG

oxaliplatin 85 mg/m2, irinotecan 165 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1

mFOLFOXIRI+Bev

mFOLFOX regimen DRUG

oxaliplatin 85 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1

mFOLFOX6+Bev

Bevacizumab DRUG

5 mg/kg on day 1

mFOLFOX6+Bev; mFOLFOXIRI+Bev

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological proof of colorectal adenocarcinoma;
• Age ≥ 18 years and ≤75 years;
• Simultaneous liver-limited metastases;
• Initially unresectable liver metastases determined by a local MDT;
• RAS mutation and BRAF V600E wild-type;
• At least one measurable liver metastasis;
• Initially resectable primary tumor or primary tumor already resected;
• World Health Organization (WHO) performance status 0-1;
• Life expectancy ≥ 3 months;
• Adequate hematologic function: absolute neutrophil count (ANC)≥1.5×109/l, platelets≥100×109/l, and hemoglobin(HB) ≥ 9g/dl;
• Adequate liver and renal function: total bilirubin ≤2.0 mg/dl, serum transaminases ≤ 5x upper limit of normal(ULN), and serum creatinine ≤ 1.5x ULN and creatinine clearance ≥ 30 ml/min;
• Written informed consent.

You may not qualify if:

• Previous systemic treatment for metastatic disease;
• Previous surgery for metastatic disease;
• Extrahepatic metastases;
• Unresectable primary tumor;
• Major cardiovascular events (myocardial infarction, severe/unstable angina, congestive heart failure, CVA) within 12 months before randomisation;
• Acute or subacute intestinal obstruction;
• Second primary malignancy within the past 5 years;
• Drug or alcohol abuse;
• No legal capacity or limited legal capacity;
• Pregnant or lactating women;
• Uncontrolled hypertension, or unsatisfactory blood pressure control with ≥3 antihypertensive drugs;
• Peripheral neuropathy;

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

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

• Jianmin Xu, MD, Ph.D.

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianmin Xu, MD, Ph.D.

CONTACT

021-64041990; xujmin@aliyun.com

Wentao Tang, MD, Ph.D.

CONTACT

021-64041990; tangwt1988@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2021
• First Posted: March 4, 2021
• Study Start: April 15, 2021
• Primary Completion: March 30, 2024
• Study Completion: March 30, 2026
• Last Updated: September 27, 2021

Record last verified: 2021-03

Locations

CN (1)