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

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Vejle, Denmark, DK-7100
    • Department of Oncology, Vejle Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to first serious adverse event	6 months after the last patient has finished chemotherapy

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: 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

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2016
• Primary Completion (Actual): August 1, 2019
• Study Completion (Actual): March 27, 2024

Study Registration Dates

• First Submitted: February 26, 2016
• First Submitted That Met QC Criteria: March 4, 2016
• First Posted (Estimated): March 10, 2016

Study Record Updates

• Last Update Posted (Actual): August 29, 2024
• Last Update Submitted That Met QC Criteria: August 28, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Antioxidants; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan; Levoleucovorin; Vitamin E; Tocopherols; Tocotrienols
• Other Study ID Numbers: FOLFOXIRI-Toco