Back to resultsSide Effects to FOLFOXIRI + Tocotrienol/Placebo as First Line Treatment of Metastatic Colorectal Cancer
Primary Purpose
Colorectal Cancer
Status
Active
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Irinotecan 165 mg/m2 iv
Oxaliplatin 85 mg/m2 iv
Calcium folinate 200 mg/m2 iv
5-fluorouracil 3200 mg/m2
Tocotrienol
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically verified colorectal adenocarcinoma.
- Patients to receive first line treatment of metastatic disease, including potentially resectable or non-resectable disease
- > 6 months without recurrence after end of adjuvant chemotherapy for radically treated stage II or III colorectal cancer
- Disease evaluable according to RECIST 1.1, but not necessarily measurable disease.
- Age 18-75 years
- Performance status (PS) 0-1. If age 71-75, then PS 0
- Life expectancy > 3 months
Organ and bone marrow function as follows:
- Neutrophil count ≥ 1.5 x 10^9/L
- Thrombocytes ≥ 100 x 10^9/L
- Total bilirubin ≤ 1.5 x upper level of normal (ULN)
- Alanine transaminase (ALAT) ≤ 2.5 x ULN (or≤ 5 x ULN in case of liver metastases)
- Fertile women must present negative pregnancy test. Male (with a female fertile partner) as well as female patients must use secure contraceptives during and 6 months after end of treatment.
- Orally and written informed consent to treatment and biobank
Exclusion Criteria:
- Primarily resectable metastases
- Chemotherapy, radiotherapy or immunotherapy within 4 weeks
- Known neuropathy ≥ grade 2
- Serious competitive medical condition
- Other concurrent malignant disease other than non-melanoma skin cancer
- Previous serious and unexpected reactions to 5-fluorouracil, calcium folinate, oxaliplatin, irinotecan or capecitabine.
- Hypersensitivity to one or more of the active substances or auxilliary agents
Sites / Locations
- Department of Oncology, Vejle Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Chemotherapy plus tocotrienol
Chemotherapy plus placebo
Arm Description
Every 2 weeks: irinotecan 165 mg/m2 iv, oxaliplatin 85 mg/m2 iv, calcium folinate 200 mg/m2 iv, and 5-fluorouracil 3200 mg/m2 as a 46 hour infusion. Daily: Tocotrienol 300 mg x 3 daily
Every 2 weeks: irinotecan 165 mg/m2 iv, oxaliplatin 85 mg/m2 iv, calcium folinate 200 mg/m2 iv, and 5-fluorouracil 3200 mg/m2 as a 46 hour infusion. Daily: Placebo x 3 daily
Outcomes
Primary Outcome Measures
Time to first serious adverse event
Secondary Outcome Measures
Number of non-planned hospitalizations calculated from date of first treatment until 1 month after completed chemotherapy
Duration of non-planned hospitalizations calculated from date of first treatment until 1 month after completed chemotherapy
Death during treatment calculated from date of first treatment until 1 month after completed chemotherapy
Response rate
Progression free survival
Overall survival
Number of patients with treatment related adverse events as assessed by CTCAE v.4.0
Quality of life as measured by combined questionnaire consisting of EORTC QLQ-C30 and CR29
Resection rate
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02705300
Brief Title
Side Effects to FOLFOXIRI + Tocotrienol/Placebo as First Line Treatment of Metastatic Colorectal Cancer
Official Title
A Randomized Investigation of Side Effects to FOLFOXIRI in Combination With Tocotrienol or Placebo as First Line Treatment of Metastatic Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 6, 2016 (Actual)
Primary Completion Date
August 2019 (Actual)
Study Completion Date
March 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vejle Hospital
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Treatment with FOLFOXIRI (5-fluorouracil, oxaliplatin, irinotecan) can be effective, but it has serious side effects, which may require hospitalization.
The purpose of this study is to investigate whether the addition of tocotrienol can reduce the side effects to FOLFOXIRI otherwise leading to hospitalization.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
70 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Chemotherapy plus tocotrienol
Arm Type
Experimental
Arm Description
Every 2 weeks: irinotecan 165 mg/m2 iv, oxaliplatin 85 mg/m2 iv, calcium folinate 200 mg/m2 iv, and 5-fluorouracil 3200 mg/m2 as a 46 hour infusion.
Daily: Tocotrienol 300 mg x 3 daily
Arm Title
Chemotherapy plus placebo
Arm Type
Placebo Comparator
Arm Description
Every 2 weeks: irinotecan 165 mg/m2 iv, oxaliplatin 85 mg/m2 iv, calcium folinate 200 mg/m2 iv, and 5-fluorouracil 3200 mg/m2 as a 46 hour infusion.
Daily: Placebo x 3 daily
Intervention Type
Drug
Intervention Name(s)
Irinotecan 165 mg/m2 iv
Intervention Description
Max. 4 months
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin 85 mg/m2 iv
Intervention Description
Max. 4 months
Intervention Type
Drug
Intervention Name(s)
Calcium folinate 200 mg/m2 iv
Intervention Description
Max. 6 months
Intervention Type
Drug
Intervention Name(s)
5-fluorouracil 3200 mg/m2
Intervention Description
Max. 6 months
Intervention Type
Dietary Supplement
Intervention Name(s)
Tocotrienol
Intervention Description
Max. 2 years or at the discretion of the investigator
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Max. 2 years or at the discretion of the investigator
Primary Outcome Measure Information:
Title
Time to first serious adverse event
Time Frame
6 months after the last patient has finished chemotherapy
Secondary Outcome Measure Information:
Title
Number of non-planned hospitalizations calculated from date of first treatment until 1 month after completed chemotherapy
Time Frame
6 months after the last patient has finished chemotherapy
Title
Duration of non-planned hospitalizations calculated from date of first treatment until 1 month after completed chemotherapy
Time Frame
6 months after the last patient has finished chemotherapy
Title
Death during treatment calculated from date of first treatment until 1 month after completed chemotherapy
Time Frame
6 months after the last patient has finished chemotherapy
Title
Response rate
Time Frame
6 months after the last patient has finished chemotherapy
Title
Progression free survival
Time Frame
6 months after the last patient has finished chemotherapy
Title
Overall survival
Time Frame
6 months after the last patient has finished chemotherapy
Title
Number of patients with treatment related adverse events as assessed by CTCAE v.4.0
Time Frame
6 months after the last patient has finished chemotherapy
Title
Quality of life as measured by combined questionnaire consisting of EORTC QLQ-C30 and CR29
Time Frame
6 months after the last patient has finished chemotherapy
Title
Resection rate
Time Frame
6 months after the last patient has finished chemotherapy
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:
Histologically or cytologically verified colorectal adenocarcinoma.
Patients to receive first line treatment of metastatic disease, including potentially resectable or non-resectable disease
> 6 months without recurrence after end of adjuvant chemotherapy for radically treated stage II or III colorectal cancer
Disease evaluable according to RECIST 1.1, but not necessarily measurable disease.
Age 18-75 years
Performance status (PS) 0-1. If age 71-75, then PS 0
Life expectancy > 3 months
Organ and bone marrow function as follows:
Neutrophil count ≥ 1.5 x 10^9/L
Thrombocytes ≥ 100 x 10^9/L
Total bilirubin ≤ 1.5 x upper level of normal (ULN)
Alanine transaminase (ALAT) ≤ 2.5 x ULN (or≤ 5 x ULN in case of liver metastases)
Fertile women must present negative pregnancy test. Male (with a female fertile partner) as well as female patients must use secure contraceptives during and 6 months after end of treatment.
Orally and written informed consent to treatment and biobank
Exclusion Criteria:
Primarily resectable metastases
Chemotherapy, radiotherapy or immunotherapy within 4 weeks
Known neuropathy ≥ grade 2
Serious competitive medical condition
Other concurrent malignant disease other than non-melanoma skin cancer
Previous serious and unexpected reactions to 5-fluorouracil, calcium folinate, oxaliplatin, irinotecan or capecitabine.
Hypersensitivity to one or more of the active substances or auxilliary agents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lars H Jensen, PhD
Organizational Affiliation
Department of Oncology, Vejle Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Louise R Larsen, MD
Organizational Affiliation
Department of Oncology, Vejle Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Oncology, Vejle Hospital
City
Vejle
ZIP/Postal Code
DK-7100
Country
Denmark
12. IPD Sharing Statement
Learn more about this trial
Side Effects to FOLFOXIRI + Tocotrienol/Placebo as First Line Treatment of Metastatic Colorectal Cancer
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