Phase II Trial of FOLFOXIGIL Versus FOLFOXIRI as First-line Therapy in Patients With mCRC

NCT ID: NCT03222089

Last Updated: 2018-03-27

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-20
• Study Completion Date: 2020-07-20

Brief Summary

A randomized phase II trial of FOLFOXIRI in Combination With GM-CSF and IL-2 (FOLFOXIGIL) Versus FOLFOXIRI as First-line Treatment for Patients With Metastatic Colorectal Cancer.

Detailed Description

The triple drug regimen FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) for the first-line treatment of metastatic colorectal cancer has shown a significant increase in response rate and overall survival compared to FOLFIRI and FOLFOX. The combination of GOLF chemotherapy with GM-CSF and IL-2（GOLFIG regimen） has shown more active than the standard FOLFOX chemotherapy in first-line mCRC patients，through the chemoimmunomodulatory effects. SO the FOLFOXIGIL chemoimmunotherapy regimen was designed with the same principle to evaluate the antitumor frontline efficacy in comparison with the FOLFOXIRI regimen as first-line treatment of mCRC patients. This is a multicenter, randomized controlled, double-blind, phase II trial.

Conditions

Metastatic Colorectal Cancer

Study Design

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

Study Groups

FOLFOXIGIL

The FOLFOXIGIL chemoimmunotherapy regimen is composed by FOLFOXIRI chemotherapy and the immunotherapy of GM-CSF and IL-2.

FOLFOXIRI: Irinotecan 165 mg/m² + oxaliplatin 85 mg/m² + Levoleucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1, repeated every 2 weeks.

GM-CSF 150ug s.c. d3-7; Interleukin-2 100MIU s.c. d8-14 and d17-d28, Repeated every 4 weeks.

Treatment will be administered until progression, patients' withdrawal of consent, unacceptable toxicity.

Group Type: EXPERIMENTAL

Irinotecan

Intervention Type: DRUG

Irinotecan 165 mg/m² 1-hour IV day 1

Oxaliplatin

Intervention Type: DRUG

oxaliplatin 85 mg/m² 2-hours IV day 1

Levoleucovorin

Intervention Type: DRUG

Levoleucovorin 200 mg/m² 2-hours IV day 1

5-FU

Intervention Type: DRUG

5-FU 2800 mg/m² 46-hours flat continuous infusion IV

GM-CSF

Intervention Type: DRUG

GM-CSF 150ug s.c. d3-7 , Repeated every 4 weeks.

IL-2

Intervention Type: DRUG

Interleukin-2 100MIU s.c. d8-14 and d17-d28, Repeated every 4 weeks.

FOLFOXIRI

Irinotecan 165 mg/m² + oxaliplatin 85 mg/m² + Levoleucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1, Repeated every 2 weeks.

Treatment will be administered until progression, patients' withdrawal of consent, unacceptable toxicity.

Group Type: ACTIVE_COMPARATOR

Irinotecan

Intervention Type: DRUG

Irinotecan 165 mg/m² 1-hour IV day 1

Oxaliplatin

Intervention Type: DRUG

oxaliplatin 85 mg/m² 2-hours IV day 1

Levoleucovorin

Intervention Type: DRUG

Levoleucovorin 200 mg/m² 2-hours IV day 1

5-FU

Intervention Type: DRUG

5-FU 2800 mg/m² 46-hours flat continuous infusion IV

Interventions

Irinotecan

Irinotecan 165 mg/m² 1-hour IV day 1

Intervention Type: DRUG

Oxaliplatin

oxaliplatin 85 mg/m² 2-hours IV day 1

Intervention Type: DRUG

Levoleucovorin

Levoleucovorin 200 mg/m² 2-hours IV day 1

Intervention Type: DRUG

5-FU

5-FU 2800 mg/m² 46-hours flat continuous infusion IV

Intervention Type: DRUG

GM-CSF

GM-CSF 150ug s.c. d3-7 , Repeated every 4 weeks.

Intervention Type: DRUG

IL-2

Interleukin-2 100MIU s.c. d8-14 and d17-d28, Repeated every 4 weeks.

Intervention Type: DRUG

Other Intervention Names

CPT11; Camptosar; L-OHP; Eloxatin; Fusilev; l-LV; 5-Fluorouracil; Granulocyte Macrophage Colony Stimulating Factor; Interleukin-2

Eligibility Criteria

Inclusion Criteria

• histological or cytological documentation of adenocarcinoma of the colon or rectum.
• unresectable metastatic disease
• age 18 to 75 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or lower if age 70 years or younger or ECOG performance status of 0 if age 71 to 75 years
• at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria measured within 4 weeks prior to registration.
• no previous chemotherapy or target therapy for metastatic disease (adjuvant chemotherapy for non-metastatic disease is allowed if terminated more than 6 months ago).
• adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:

• Leukocytes ≥ 3.0 x109/ L, absolute neutrophil count (ANC) ≥ 1.5 x109/ L, platelet count ≥ 100 x109/ L, hemoglobin (Hb) ≥9g/ dL.
• Total bilirubin ≤ 1.5 x the upper limit of normal (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN.
• Alkaline phosphatase limit ≤ 5x ULN.
• Amylase and lipase ≤ 1.5 x the ULN.
• Serum creatinine ≤ 1.5 x the ULN.
• Calculated creatinine clearance or 24 hour creatinine clearance ≥ 50 mL/ min.

Exclusion Criteria

• previous palliative chemotherapy for metastatic disease
• previous chemotherapy including irinotecan or oxaliplatin
• symptomatic cardiac disease, myocardial infarction in the last 24 months or uncontrolled arrhythmia
• active infections
• pregnancy or lactation at the time of study entry.
• inflammatory bowel disease
• major autoimmune diseases
• acquired immunosuppression (AIDS or major immunosuppressive agents)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fujian Cancer Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rongbo Lin, MD

Role: STUDY_CHAIR

Fujian Cancer Hospital

Locations

Rongbo Lin

Fuzhou, Fujian, China

Countries

China

Other Identifiers

FNF-006

Identifier Type: -

Identifier Source: org_study_id