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

Vejle Hospital

Status and phase: Completed; Phase 2

Conditions: Colorectal Cancer

Treatments: Drug: 5-fluorouracil 3200 mg/m2; Drug: Placebo; Drug: Irinotecan 165 mg/m2 iv; Dietary Supplement: Tocotrienol; Drug: Calcium folinate 200 mg/m2 iv; Drug: Oxaliplatin 85 mg/m2 iv

Study type: Interventional

Funder types: Other

Identifiers

NCT02705300

FOLFOXIRI-Toco

Details and patient eligibility

About

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.

Enrollment: 70 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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70 participants in 2 patient groups, including a placebo group

Chemotherapy plus tocotrienol

Experimental group

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

Treatment:

Drug: Oxaliplatin 85 mg/m2 iv

Drug: Calcium folinate 200 mg/m2 iv

Dietary Supplement: Tocotrienol

Drug: Irinotecan 165 mg/m2 iv

Drug: 5-fluorouracil 3200 mg/m2

Chemotherapy plus placebo

Placebo Comparator group

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

Treatment:

Drug: Oxaliplatin 85 mg/m2 iv

Drug: Calcium folinate 200 mg/m2 iv

Drug: Placebo

Drug: Irinotecan 165 mg/m2 iv

Drug: 5-fluorouracil 3200 mg/m2