Clinical trial NCT04245865: Tocotrienol and Bevacizumab in Metastatic Colorectal Cancer
Official title: Tocotrienol and Bevacizumab in Metastatic Colorectal Cancer. A Randomized Phase II Marker Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Colorectal Cancer Metastatic
Keywords: Colorectal cancer
Tocotrienol
Natural killer cells
Circulating tumor DNA
Lead sponsor: Vejle Hospital
Sponsor class: OTHER
First posted: 2020-01-29
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: The rate of progression free patients at six months
timeFrame: Six months after enrollment of the last patient
Secondary outcomes:
measure: Time to first serious adverse event according to CTCAE 5.0
timeFrame: Six months after enrollment of the last patient
measure: Response rate as measured by RECIST 1.1
timeFrame: Six months after enrollment of the last patient
measure: Overall survival
timeFrame: 12 months after enrollment of the last patient
Other outcomes:
Locations:
city: Vejle
country: Denmark
facility: Department of Oncology, Vejle Hospital
Study officials:
affiliation: Department of Oncology, Vejle Hospital - University Hospital of Southern Denmark
name: Torben F Hansen, MD, PhD
role: STUDY_CHAIR
References: