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

NCT03222089 | Withdrawn Phase 2

• 1 other identifier: FNF-006
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) rate at 10 months

  PFS by investigator-reported measurements according to CT image. PFS was calculated from the day of randomization to the date of first documented progression disease (PD) , or death from any cause. PD was defined as Overall Response by RECIST criteria v1.1 according to CT image.

  PFS rate at 10 months from study entry

Secondary Outcomes (5)

• Response rate

  up to 12 months

• Toxicity

  up to 12 months

• Overall survival time

  Up to 30 months

• Progression free survival

  Up to 18 months

• Quality of life (QLQ C30)

  Quality of life was evaluated every 2 weeks during treatment and every 8 weeks during follow up (36 months)

Study Arms (2)

FOLFOXIGIL

EXPERIMENTAL

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.

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

FOLFOXIRI

ACTIVE COMPARATOR

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.

Drug: Irinotecan; Drug: Oxaliplatin; Drug: Levoleucovorin; Drug: 5-FU

Interventions

Irinotecan DRUG

Irinotecan 165 mg/m² 1-hour IV day 1

Also known as: CPT11, Camptosar

FOLFOXIGIL; FOLFOXIRI

Oxaliplatin DRUG

oxaliplatin 85 mg/m² 2-hours IV day 1

Also known as: L-OHP, Eloxatin

FOLFOXIGIL; FOLFOXIRI

Levoleucovorin DRUG

Levoleucovorin 200 mg/m² 2-hours IV day 1

Also known as: Fusilev, l-LV

FOLFOXIGIL; FOLFOXIRI

5-FU DRUG

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

Also known as: 5-Fluorouracil

FOLFOXIGIL; FOLFOXIRI

GM-CSF DRUG

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

Also known as: Granulocyte Macrophage Colony Stimulating Factor

FOLFOXIGIL

IL-2 DRUG

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

Also known as: Interleukin-2

FOLFOXIGIL

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 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Fujian Cancer Hospital: lead

Study Sites (1)

Rongbo Lin

Fuzhou, Fujian, 350014, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Irinotecan; Oxaliplatin; Levoleucovorin; Fluorouracil; Granulocyte-Macrophage Colony-Stimulating Factor; Interleukin-2

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)

Camptothecin; Alkaloids; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Leucovorin; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Interleukins; Lymphokines

Study Officials

• Rongbo Lin, MD

  Fujian Cancer Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2017
• First Posted: July 19, 2017
• Study Start: July 20, 2017
• Primary Completion: July 20, 2019
• Study Completion: July 20, 2020
• Last Updated: March 27, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)