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

Fujian Provincial Cancer Hospital

Status and phase: Withdrawn; Phase 2

Conditions: Metastatic Colorectal Cancer

Treatments: Drug: GM-CSF; Drug: Irinotecan; Drug: IL-2; Drug: Levoleucovorin; Drug: 5-FU; Drug: Oxaliplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT03222089

FNF-006

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

FOLFOXIGIL

Experimental group

Description:

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.

Treatment:

Drug: Oxaliplatin

Drug: 5-FU

Drug: IL-2

Drug: Levoleucovorin

Drug: Irinotecan

Drug: GM-CSF

FOLFOXIRI

Active Comparator group

Description:

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.

Treatment:

Drug: Oxaliplatin

Drug: 5-FU

Drug: Levoleucovorin

Drug: Irinotecan