Tocotrienol and Bevacizumab in Metastatic Colorectal Cancer

NCT ID: NCT04245865

Last Updated: 2025-04-27

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 83 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-26
• Study Completion Date: 2025-12-31

Brief Summary

This double blind, randomized phase II trial will investigate whether the addition of tocotrienol will improve the effect and lower the toxicity of standard chemotherapy and bevacizumab. Half of the patients will receive tocotrienol and the other half placebo. Treatment is planned for a period of maximum six months and will be discontinued earlier in case of progression or unacceptable toxicity.

Conditions

Colorectal Cancer Metastatic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm A, standard treatment + tocotrienol

Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + tocotrienol OR capecitabine + bevacizumab + tocotrienol

Group Type: EXPERIMENTAL

Fluorouracil

Intervention Type: DRUG

2800 mg/m2 iv

Calcium folinate

Intervention Type: DRUG

400 mg/m2 iv

Oxaliplatin

Intervention Type: DRUG

85 mg/m2 iv

Bevacizumab

Intervention Type: DRUG

5 mg/kg OR 7.5 mg/kg iv

Capecitabine

Intervention Type: DRUG

2000 mg/m2 orally daily for two weeks

Tocotrienol

Intervention Type: DIETARY_SUPPLEMENT

300 mg orally x 3 daily

Arm B, standard treatment + placebo

Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + placebo OR capecitabine + bevacizumab + placebo

Group Type: PLACEBO_COMPARATOR

Fluorouracil

Intervention Type: DRUG

2800 mg/m2 iv

Calcium folinate

Intervention Type: DRUG

400 mg/m2 iv

Oxaliplatin

Intervention Type: DRUG

85 mg/m2 iv

Bevacizumab

Intervention Type: DRUG

5 mg/kg OR 7.5 mg/kg iv

Capecitabine

Intervention Type: DRUG

2000 mg/m2 orally daily for two weeks

Placebo

Intervention Type: OTHER

Placebo orally x 3 daily

Interventions

Fluorouracil

2800 mg/m2 iv

Intervention Type: DRUG

Calcium folinate

400 mg/m2 iv

Intervention Type: DRUG

Oxaliplatin

85 mg/m2 iv

Intervention Type: DRUG

Bevacizumab

5 mg/kg OR 7.5 mg/kg iv

Intervention Type: DRUG

Capecitabine

2000 mg/m2 orally daily for two weeks

Intervention Type: DRUG

Tocotrienol

300 mg orally x 3 daily

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Placebo orally x 3 daily

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Histopathologically verified adenocarcinoma of the colon or rectum
• Metastatic disease
• Planned treatment with FOLFOX or capecitabine combined with bevacizumab
• Evaluable disease according to RECIST 1.1
• Performance status 0-2
• Expected survival ≥ 3 months
• Patient acceptance to collection of blood samples for translational research
• Age ≥ 18 years
• Contraception during and 6 months after last dose for women of childbearing potential (less than one year amenorrhea and not undergone hysterectomy, bilateral salpingectomy or bilateral oophorectomy) and for male patients with a fertile partner. Hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence is accepted.
• Adequate bone marrow function, liver function, and renal function (within 7 days prior to inclusion):

• WBC ≥ 3.0 x 109/l or neutrophils (ANC) ≥ 1.5 x 10^9/l
• Platelet count ≥ 100 x 10^9/l
• Hemoglobin ≥ 6.0 mmol/l
• Serum bilirubin ≤ 2.0 x ULN
• Serum transaminase ≤ 2.5 x ULN
• Serum creatinine ≤ 1.5 ULN
• Urine dipstick for protein ≤ 2+, if the dipstick shows protein ≥ 2+, 24 hour urine testing must be performed and show protein contents ≤ 1g.
• Written and orally informed consent

Exclusion Criteria

• Other active malignant disease within 5 years prior to inclusion in the study.
• Other experimental therapy within 28 days prior to treatment initiation.
• Underlying medical disease not adequately treated.
• Surgery, including open biopsy, within 4 weeks prior to first dose of bevacizumab.
• Cerebral vascular attack, transient ischemic attack or subarachnoid hemorrhage within six months before start of treatment
• Bleeding tumor
• Pregnant or breastfeeding women
• Fertile patients not willing to use effective methods of contraception during treatment and for six months after end of treatment.
• Hypersensitivity to one or more active substances or auxiliary substances

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vejle Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Torben F Hansen, MD, PhD

Role: STUDY_CHAIR

Department of Oncology, Vejle Hospital - University Hospital of Southern Denmark

Locations

Department of Oncology, Vejle Hospital

Vejle, , Denmark

Countries

Denmark

Other Identifiers

Toco-CoR

Identifier Type: -

Identifier Source: org_study_id