Tocotrienol and Bevacizumab in Metastatic Colorectal Cancer

Phase 2

Active, not recruiting

• Conditions: Colorectal Cancer Metastatic
• Interventions: Drug: Fluorouracil; Drug: Calcium folinate; Drug: Oxaliplatin; Drug: Bevacizumab; Drug: Capecitabine; Dietary Supplement: Tocotrienol; Other: Placebo

• Registration Number: NCT04245865
• Lead Sponsor: Vejle Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-01-27
• Study First Submitted QC: 2020-01-27
• Study First Posted: 2020-01-29
• Study Start: 2020-06-26
• Primary Completion: 2025-03-31
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-25
• Last Update Posted: 2025-04-27
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 83

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A, standard treatment + tocotrienol	Fluorouracil	Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + tocotrienol OR capecitabine + bevacizumab + tocotrienol
Arm A, standard treatment + tocotrienol	Calcium folinate	Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + tocotrienol OR capecitabine + bevacizumab + tocotrienol
Arm A, standard treatment + tocotrienol	Oxaliplatin	Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + tocotrienol OR capecitabine + bevacizumab + tocotrienol
Arm A, standard treatment + tocotrienol	Bevacizumab	Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + tocotrienol OR capecitabine + bevacizumab + tocotrienol
Arm A, standard treatment + tocotrienol	Capecitabine	Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + tocotrienol OR capecitabine + bevacizumab + tocotrienol
Arm A, standard treatment + tocotrienol	Tocotrienol	Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + tocotrienol OR capecitabine + bevacizumab + tocotrienol
Arm B, standard treatment + placebo	Fluorouracil	Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + placebo OR capecitabine + bevacizumab + placebo
Arm B, standard treatment + placebo	Calcium folinate	Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + placebo OR capecitabine + bevacizumab + placebo
Arm B, standard treatment + placebo	Placebo	Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + placebo OR capecitabine + bevacizumab + placebo
Arm B, standard treatment + placebo	Bevacizumab	Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + placebo OR capecitabine + bevacizumab + placebo
Arm B, standard treatment + placebo	Oxaliplatin	Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + placebo OR capecitabine + bevacizumab + placebo
Arm B, standard treatment + placebo	Capecitabine	Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + placebo OR capecitabine + bevacizumab + placebo

Primary Outcome Measures

Name	Time	Method
The rate of progression free patients at six months	Six months after enrollment of the last patient

Secondary Outcome Measures

Name	Time	Method
Time to first serious adverse event according to CTCAE 5.0	Six months after enrollment of the last patient	CTCAE=Common Terminology Criteria for Adverse Events
Overall survival	12 months after enrollment of the last patient
Response rate as measured by RECIST 1.1	Six months after enrollment of the last patient	RECIST=Response evaluation criteria in solid tumors

Trial Locations

Locations (1)

Department of Oncology, Vejle Hospital; 🇩🇰 Vejle, Denmark