A Study of FOLFOXIRI Plus Cetuximab vs. FOLFOXIRI Plus Bevacizumab

NCT ID: NCT02515734

Last Updated: 2015-08-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 360 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2020-06-30

Brief Summary

This study is to verify the advantage of FOLFOXIRI plus cetuximab over FOLFOXIRI plus bevacizumab as the first-line therapy in metastatic colorectal cancer patients with RAS wild-type tumors.

Detailed Description

This study is to verify the advantage of FOLFOXIRI plus cetuximab over FOLFOXIRI plus bevacizumab as the first-line therapy in metastatic colorectal cancer patients with RAS wild-type tumors. In this study the investigators employed deepness of response as a primary endpoint.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

FOLFOXIRI+Bmab

Patients in the FOLFOXIRI + Bmab group receive until 12 cycles of FOLFOXIRI plus bevacizumab, consisting of a 30-minute infusion of bevacizumab at a dose of 5 mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and bevacizumab every 14 days until disease progression.

Group Type: ACTIVE_COMPARATOR

fluorouracil

Intervention Type: DRUG

Leucovorin

Intervention Type: DRUG

irinotecan

Intervention Type: DRUG

oxaliplatin

Intervention Type: DRUG

bevacizumab

Intervention Type: BIOLOGICAL

FOLFOXIRI+Cmab

Patients in the experimental group received until 12 cycles of FOLFOXIRI plus cetuximab, consisting of a 30-minute infusion of cetuximab first time at a dose of 400 mg per kilogram, after the second time at a dose of 250mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and cetuximab every 14 days until disease progression.

Group Type: EXPERIMENTAL

fluorouracil

Intervention Type: DRUG

Leucovorin

Intervention Type: DRUG

irinotecan

Intervention Type: DRUG

oxaliplatin

Intervention Type: DRUG

cetuximab

Intervention Type: BIOLOGICAL

Interventions

fluorouracil

Intervention Type: DRUG

Leucovorin

Intervention Type: DRUG

irinotecan

Intervention Type: DRUG

oxaliplatin

Intervention Type: DRUG

bevacizumab

Intervention Type: BIOLOGICAL

cetuximab

Intervention Type: BIOLOGICAL

Other Intervention Names

5-fluorouracil; 5-FU; Levofolinate; CPT-11; eloxatin

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed colorectal cancer
• RAS wild-type
• Measurable lesion by RECIST (Ver.1.1)
• No past history of chemotherapy in the case of unresectable primary lesion/distant metastasis/lymph node metastasis.In the case of recurrence, no treatment for the first recurrence lesion after operation
• Eastern Cooperative Oncology Group (ECOG) Performance status 0-1.The case >=71 years is PS0.
• Life expectancy of more than 6 months
• Patients have enough organ function for study treatment within 14 days before enrollment;

1. White blood cell (WBC)>=3,000/mm3, <12,000/mm3.

2. Neu>=1,500/mm3.

3. Platelet count (PLT) >=10.0x104/mm3.

4. Hb>=9.0g/dL.

5. Total Bilirubin<=1.5x Upper Limited Normal (ULN)

6. aspartate aminotransferase (AST) <=2.5xULN.

7. alanine aminotransferase (ALT) <=2.5xULN.

8. Creatinine<=1.5xULN.

9. Proteinuria<=1+.

10. prothrombin time-international normalized ratio (PT-INR) <=1.5

• Must be able to swallow tablets
• Written informed consent

Exclusion Criteria

• Synchronous multiple malignancy or metachronous multiple malignancy within 5 years disease free interval
• Lynch syndrome
• Brain metastases
• Infectious disease
• Interstitial lung disease or pulmonary fibrosis
• Comorbidity or history of serious heart failure
• History of thromboembolic events
• Cerebrovascular disease
• History of hemoptysis/hematemesis
• Uncontrolled hypertension (systolic BP>180mmHg, or diastolic BP>100mmHg)
• Sensory alteration or paresthesia interfering with function
• Large quantity of pleural, abdominal or cardiac effusion
• Severe comorbidity (renal failure, liver failure, hypertension, etc)
• Prior radiotherapy for primary and metastases leision
• Men/women who are unwilling to avoid pregnancy
• Women who are pregnant or breastfeeding
• Women with a positive pregnancy test
• History of severe allergy
• HBsAg positive or active viral hepatitis
• Administration of blood products/ Granulocyte-Colony Stimulating Factor (G-CSF), and blood transfusion within 14 days
• Surgical procedure or such as skin-open biopsy, trauma surgery, or other more intensive surgery within 28 days
• Systematic administration of antiplatelet drug or non steroid anti-inflammatory drugs (NSAIDs)
• Diathesis of bleeding (history of hemoptysis, including cavitation and/or necrosis in lung metastasis confirmed by imaging), coagulopathy
• History of gastrointestinal perforation within 1 year
• Unhealed traumatic bone fracture
• Uncontrolled diarrhea
• History of organ recipient
• Prior cetuximab/bevacizumab/Irinotecan/Oxaliplatin treatment (Adjuvant therapy by Oxaliplatin is excluded)
• Administration of atazanavir sulfate
• Jaundice
• Ileus or bowel obstruction
• Clinical diagnosis of Alzheimer's Disease
• Insulin dependent diabetes
• Thyroid disease
• Any other cases who are regarded as inadequate for study enrollment by investigators

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Japan Clinical Cancer Research Organization

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Toshifusa Nakajima, MD

Role: STUDY_DIRECTOR

Japan Clinical Cancer Research Organization

Central Contacts

Masashi Fujii, MD

Role: CONTACT

masashi.fujii@gioncology.jp

+81-3-5579-9882

Sachika Koyama, Ms

Role: CONTACT

cc13.dc@jaccro.or.jp

+81-3-5579-9882

Other Identifiers

JACCRO CC-13

Identifier Type: -

Identifier Source: org_study_id