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

NCT02705300 | Completed Phase 2

• 1 other identifier: FOLFOXIRI-Toco
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Time to first serious adverse event

  6 months after the last patient has finished chemotherapy

Secondary Outcomes (9)

• 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

Study Arms (2)

Chemotherapy plus tocotrienol

EXPERIMENTAL

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; Drug: Oxaliplatin 85 mg/m2 iv; Drug: Calcium folinate 200 mg/m2 iv; Drug: 5-fluorouracil 3200 mg/m2; Dietary Supplement: Tocotrienol

Chemotherapy plus placebo

PLACEBO COMPARATOR

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; Drug: Oxaliplatin 85 mg/m2 iv; Drug: Calcium folinate 200 mg/m2 iv; Drug: 5-fluorouracil 3200 mg/m2; Drug: Placebo

Interventions

Irinotecan 165 mg/m2 iv DRUG

Max. 4 months

Chemotherapy plus placebo; Chemotherapy plus tocotrienol

Oxaliplatin 85 mg/m2 iv DRUG

Max. 4 months

Chemotherapy plus placebo; Chemotherapy plus tocotrienol

Calcium folinate 200 mg/m2 iv DRUG

Max. 6 months

Chemotherapy plus placebo; Chemotherapy plus tocotrienol

5-fluorouracil 3200 mg/m2 DRUG

Max. 6 months

Chemotherapy plus placebo; Chemotherapy plus tocotrienol

Tocotrienol DIETARY_SUPPLEMENT

Max. 2 years or at the discretion of the investigator

Chemotherapy plus tocotrienol

Placebo DRUG

Max. 2 years or at the discretion of the investigator

Chemotherapy plus placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vejle Hospital: lead

Study Sites (1)

Department of Oncology, Vejle Hospital

Vejle, DK-7100, Denmark

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Irinotecan; Oxaliplatin; Leucovorin; Fluorouracil; Tocotrienols

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; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Vitamin E; Benzopyrans; Pyrans

Study Officials

• Lars H Jensen, PhD

  Department of Oncology, Vejle Hospital

  STUDY CHAIR

• Louise R Larsen, MD

  Department of Oncology, Vejle Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2016
• First Posted: March 10, 2016
• Study Start: May 6, 2016
• Primary Completion: August 1, 2019
• Study Completion: March 27, 2024
• Last Updated: August 29, 2024

Record last verified: 2024-08

Locations

DK (1)