Clinical trial NCT02705300: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Vejle Hospital
Sponsor class: OTHER
First posted: 2016-03-10
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Time to first serious adverse event
timeFrame: 6 months after the last patient has finished chemotherapy
Secondary outcomes:
measure: Number of non-planned hospitalizations calculated from date of first treatment until 1 month after completed chemotherapy
timeFrame: 6 months after the last patient has finished chemotherapy
measure: Duration of non-planned hospitalizations calculated from date of first treatment until 1 month after completed chemotherapy
timeFrame: 6 months after the last patient has finished chemotherapy
measure: Death during treatment calculated from date of first treatment until 1 month after completed chemotherapy
timeFrame: 6 months after the last patient has finished chemotherapy
measure: Response rate
timeFrame: 6 months after the last patient has finished chemotherapy
measure: Progression free survival
timeFrame: 6 months after the last patient has finished chemotherapy
measure: Overall survival
timeFrame: 6 months after the last patient has finished chemotherapy
measure: Number of patients with treatment related adverse events as assessed by CTCAE v.4.0
timeFrame: 6 months after the last patient has finished chemotherapy
measure: Quality of life as measured by combined questionnaire consisting of EORTC QLQ-C30 and CR29
timeFrame: 6 months after the last patient has finished chemotherapy
measure: Resection rate
timeFrame: 6 months after the last patient has finished chemotherapy
Other outcomes:
Locations:
city: Vejle
country: Denmark
facility: Department of Oncology, Vejle Hospital
Study officials:
affiliation: Department of Oncology, Vejle Hospital
name: Lars H Jensen, PhD
role: STUDY_CHAIR
affiliation: Department of Oncology, Vejle Hospital
name: Louise R Larsen, MD
role: PRINCIPAL_INVESTIGATOR
References: