Tocotrienol and Bevacizumab in Metastatic Colorectal Cancer

NCT04245865 | Active Not Recruiting Phase 2

• 1 other identifier: Toco-CoR
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

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

Keywords

Colorectal cancer; Tocotrienol; Natural killer cells; Circulating tumor DNA

Outcome Measures

Primary Outcomes (1)

• The rate of progression free patients at six months

  Six months after enrollment of the last patient

Secondary Outcomes (3)

• Time to first serious adverse event according to CTCAE 5.0

  Six months after enrollment of the last patient

• Response rate as measured by RECIST 1.1

  Six months after enrollment of the last patient

• Overall survival

  12 months after enrollment of the last patient

Study Arms (2)

Arm A, standard treatment + tocotrienol

EXPERIMENTAL

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

Drug: Fluorouracil; Drug: Calcium folinate; Drug: Oxaliplatin; Drug: Bevacizumab; Drug: Capecitabine; Dietary Supplement: Tocotrienol

Arm B, standard treatment + placebo

PLACEBO COMPARATOR

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

Drug: Fluorouracil; Drug: Calcium folinate; Drug: Oxaliplatin; Drug: Bevacizumab; Drug: Capecitabine; Other: Placebo

Interventions

Fluorouracil DRUG

2800 mg/m2 iv

Arm A, standard treatment + tocotrienol; Arm B, standard treatment + placebo

Calcium folinate DRUG

400 mg/m2 iv

Arm A, standard treatment + tocotrienol; Arm B, standard treatment + placebo

Oxaliplatin DRUG

85 mg/m2 iv

Arm A, standard treatment + tocotrienol; Arm B, standard treatment + placebo

Bevacizumab DRUG

5 mg/kg OR 7.5 mg/kg iv

Arm A, standard treatment + tocotrienol; Arm B, standard treatment + placebo

Capecitabine DRUG

2000 mg/m2 orally daily for two weeks

Arm A, standard treatment + tocotrienol; Arm B, standard treatment + placebo

Tocotrienol DIETARY_SUPPLEMENT

300 mg orally x 3 daily

Arm A, standard treatment + tocotrienol

Placebo OTHER

Placebo orally x 3 daily

Arm B, standard treatment + placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vejle Hospital: lead

Study Sites (1)

Department of Oncology, Vejle Hospital

Vejle, 7100, Denmark

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Fluorouracil; Leucovorin; Oxaliplatin; Bevacizumab; Capecitabine; Tocotrienols

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Vitamin E; Benzopyrans; Pyrans

Study Officials

• Torben F Hansen, MD, PhD

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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2020
• First Posted: January 29, 2020
• Study Start: June 26, 2020
• Primary Completion: March 31, 2025
• Study Completion: December 1, 2025
• Last Updated: April 27, 2025

Record last verified: 2025-04

Locations

DK (1)