Side Effects to FOLFOXIRI + Tocotrienol/Placebo as First Line Treatment of Metastatic Colorectal Cancer

Sponsor

Vejle Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02705300

Collaborator

(none)

Enrollment

Location

Arms

105.8

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: Irinotecan 165 mg/m2 iv Drug: Oxaliplatin 85 mg/m2 iv Drug: Calcium folinate 200 mg/m2 iv Drug: 5-fluorouracil 3200 mg/m2 Dietary Supplement: Tocotrienol Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized Investigation of Side Effects to FOLFOXIRI in Combination With Tocotrienol or Placebo as First Line Treatment of Metastatic Colorectal Cancer

Actual Study Start Date :

May 6, 2016

Actual Primary Completion Date :

Aug 1, 2019

Anticipated Study Completion Date :

Mar 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chemotherapy plus tocotrienol 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	Drug: Irinotecan 165 mg/m2 iv Max. 4 months Drug: Oxaliplatin 85 mg/m2 iv Max. 4 months Drug: Calcium folinate 200 mg/m2 iv Max. 6 months Drug: 5-fluorouracil 3200 mg/m2 Max. 6 months Dietary Supplement: Tocotrienol Max. 2 years or at the discretion of the investigator
Placebo Comparator: Chemotherapy plus placebo 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	Drug: Irinotecan 165 mg/m2 iv Max. 4 months Drug: Oxaliplatin 85 mg/m2 iv Max. 4 months Drug: Calcium folinate 200 mg/m2 iv Max. 6 months Drug: 5-fluorouracil 3200 mg/m2 Max. 6 months Drug: Placebo Max. 2 years or at the discretion of the investigator

Arm

Intervention/Treatment

Experimental: Chemotherapy plus tocotrienol

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

Drug: Irinotecan 165 mg/m2 iv

Max. 4 months

Drug: Oxaliplatin 85 mg/m2 iv

Max. 4 months

Drug: Calcium folinate 200 mg/m2 iv

Max. 6 months

Drug: 5-fluorouracil 3200 mg/m2

Max. 6 months

Dietary Supplement: Tocotrienol

Max. 2 years or at the discretion of the investigator

Placebo Comparator: Chemotherapy plus placebo

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

Drug: Irinotecan 165 mg/m2 iv

Max. 4 months

Drug: Oxaliplatin 85 mg/m2 iv

Max. 4 months

Drug: Calcium folinate 200 mg/m2 iv

Max. 6 months

Drug: 5-fluorouracil 3200 mg/m2

Max. 6 months

Drug: Placebo

Max. 2 years or at the discretion of the investigator

Outcome Measures

Primary Outcome Measures

Time to first serious adverse event [6 months after the last patient has finished chemotherapy]

Secondary Outcome Measures

Number of non-planned hospitalizations calculated from date of first treatment until 1 month after completed chemotherapy [6 months after the last patient has finished chemotherapy]
Duration of non-planned hospitalizations calculated from date of first treatment until 1 month after completed chemotherapy [6 months after the last patient has finished chemotherapy]
Death during treatment calculated from date of first treatment until 1 month after completed chemotherapy [6 months after the last patient has finished chemotherapy]
Response rate [6 months after the last patient has finished chemotherapy]
Progression free survival [6 months after the last patient has finished chemotherapy]
Overall survival [6 months after the last patient has finished chemotherapy]
Number of patients with treatment related adverse events as assessed by CTCAE v.4.0 [6 months after the last patient has finished chemotherapy]
Quality of life as measured by combined questionnaire consisting of EORTC QLQ-C30 and CR29 [6 months after the last patient has finished chemotherapy]
Resection rate [6 months after the last patient has finished chemotherapy]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Oncology, Vejle Hospital	Vejle		Denmark	DK-7100

Sponsors and Collaborators

Vejle Hospital

Investigators

Study Chair: Lars H Jensen, PhD, Department of Oncology, Vejle Hospital
Principal Investigator: Louise R Larsen, MD, Department of Oncology, Vejle Hospital