Back to resultsPhase II Trial of FOLFOXIGIL Versus FOLFOXIRI as First-line Therapy in Patients With mCRC
Primary Purpose
Metastatic Colorectal Cancer
Status
Withdrawn
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Irinotecan
Oxaliplatin
Levoleucovorin
5-FU
GM-CSF
IL-2
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer
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)
Sites / Locations
- Rongbo Lin
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
FOLFOXIGIL
FOLFOXIRI
Arm 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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Response rate
CR + PR rate according to the RECIST version 1.1 guidelines.
Toxicity
Toxicity assessed using the NCI common toxicity criteria, version 4.01
Overall survival time
OS was calculated from the date of randomization to death from any cause.
Progression free survival
PFS was calculated from the day of randomization to the date of first documented progression, or death from any cause.
Quality of life (QLQ C30)
Scores according to EORTC QLQ-C30 scoring manual
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03222089
Brief Title
Phase II Trial of FOLFOXIGIL Versus FOLFOXIRI as First-line Therapy in Patients With mCRC
Official Title
FOLFOXIRI in Combination With GM-CSF and IL-2 (FOLFOXIGIL) Versus FOLFOXIRI as First-line Treatment for Patients With Metastatic Colorectal Cancer: a Phase II Trial by the FNF Team.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Withdrawn
Why Stopped
Another study enrolling the similar group of patient are ongoing
Study Start Date
July 20, 2017 (Anticipated)
Primary Completion Date
July 20, 2019 (Anticipated)
Study Completion Date
July 20, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fujian Cancer Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
FOLFOXIGIL
Arm Type
Experimental
Arm 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.
Arm Title
FOLFOXIRI
Arm Type
Active Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
CPT11, Camptosar
Intervention Description
Irinotecan 165 mg/m² 1-hour IV day 1
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
L-OHP, Eloxatin
Intervention Description
oxaliplatin 85 mg/m² 2-hours IV day 1
Intervention Type
Drug
Intervention Name(s)
Levoleucovorin
Other Intervention Name(s)
Fusilev, l-LV
Intervention Description
Levoleucovorin 200 mg/m² 2-hours IV day 1
Intervention Type
Drug
Intervention Name(s)
5-FU
Other Intervention Name(s)
5-Fluorouracil
Intervention Description
5-FU 2800 mg/m² 46-hours flat continuous infusion IV
Intervention Type
Drug
Intervention Name(s)
GM-CSF
Other Intervention Name(s)
Granulocyte Macrophage Colony Stimulating Factor
Intervention Description
GM-CSF 150ug s.c. d3-7 , Repeated every 4 weeks.
Intervention Type
Drug
Intervention Name(s)
IL-2
Other Intervention Name(s)
Interleukin-2
Intervention Description
Interleukin-2 100MIU s.c. d8-14 and d17-d28, Repeated every 4 weeks.
Primary Outcome Measure Information:
Title
Progression-free survival (PFS) rate at 10 months
Description
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.
Time Frame
PFS rate at 10 months from study entry
Secondary Outcome Measure Information:
Title
Response rate
Description
CR + PR rate according to the RECIST version 1.1 guidelines.
Time Frame
up to 12 months
Title
Toxicity
Description
Toxicity assessed using the NCI common toxicity criteria, version 4.01
Time Frame
up to 12 months
Title
Overall survival time
Description
OS was calculated from the date of randomization to death from any cause.
Time Frame
Up to 30 months
Title
Progression free survival
Description
PFS was calculated from the day of randomization to the date of first documented progression, or death from any cause.
Time Frame
Up to 18 months
Title
Quality of life (QLQ C30)
Description
Scores according to EORTC QLQ-C30 scoring manual
Time Frame
Quality of life was evaluated every 2 weeks during treatment and every 8 weeks during follow up (36 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rongbo Lin, MD
Organizational Affiliation
Fujian Cancer Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Rongbo Lin
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350014
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Phase II Trial of FOLFOXIGIL Versus FOLFOXIRI as First-line Therapy in Patients With mCRC
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