Bevacizumab and Tocotrienol in Recurrent Ovarian Cancer

Bevacizumab and Tocotrienol in Recurrent Ovarian Cancer: A Marker Based Phase II Trial

A recent study at the Department of Oncology, Vejle Hospital (NCT02399592), investigated bevacizumab and tocotrienol in ovarian cancer patients and concurrently monitored the level of methylated HOXA9 circulating tumor DNA (HOXA9 meth-ctDNA) in the blood.

The rate of disease control was 70% with better results than other studies using bevacizumab alone. The toxicity was very low and attributed to bevacizumab only.

When the study results were worked up they showed that patients with a significant increase of HOXA9 meth-ctDNA after the first cycle of treatment did not benefit from the treatment whereas those with stable or decreasing HOXA9 meth-ctDNA did.

Therefore, in the current study patients with a high increase of HOXA9 meth-ctDNA after the first treatment cycle will discontinue treatment, as it is then considered ineffective. The remaining patients may achieve prolonged survival as predicted by their level of HOXA9 meth-ctDNA.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer Recurrent
• Intervention / Treatment: Drug: Bevacizumab; Dietary supplement: Tocotrienol

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Vejle, Denmark, 7100
    • Department of Oncology, Vejle Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed epithelial ovarian cancer, primary fallopian or primary peritoneal cancer.
• Platinum resistant epithelial ovarian cancer treated with at least two different previous chemotherapeutic regimens
• Progression on previous treatment. Previous treatment with bevacizumab is allowed.
• Measurable disease by the RECIST 1.1 criteria or evaluable by the GCIG CA-125 criteria.
• Age ≥ 18 years.
• Performance status 0-2.

• Adequate bone marrow function, liver function, and renal function (within 7 days prior to inclusion):

  • WBC ≥ 3.0 x 10^9/l or neutrophils (ANC) ≥ 1.5 x 10^9/l
  • Platelet count ≥ 100 x 10^9/l
  • Hemoglobin ≥ 6 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 < 1 g.
• Written informed consent

Exclusion Criteria:

• Other malignant disease within 3 years prior to inclusion in the study, except curatively treated basal cell or squamous cell carcinoma of the skin.
• Other experimental therapy or participation in another clinical trial within 28 days prior to treatment initiation.
• Intestinal infiltration or infiltration in major blood vessels at the discretion of the treating physician.
• Underlying medical disease not adequately treated (diabetes, cardiac disease).
• Uncontrolled hypertension (BP > 150/100 despite antihypertensive treatment).
• Surgery including open biopsy, within 4 weeks prior to first dose of bevacizumab.
• Cerebral vascular attack, transient ischemic attack or subarachnoid hemorrhage within 6 months before start of treatment.

• Clinical significant cardiovascular disease, including:

  • Myocardial infarction or unstable angina within 6 months before start of treatment
  • New York Heart Association (NYHA) class ≥ 2
  • Poorly controlled cardiac arrhythmia despite medication
  • Peripheral vascular disease grade ≥ 3
• Allergy to active substance or any of the auxiliary agents
• Bleeding tumor
• Pregnant or breast-feeding patients. For fertile women a negative pregnancy test at screening is mandatory.
• Fertile patients not willing to use effective methods of contraception during treatment and for 6 months after the end of treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Discontinue treatment after first treatment cycle	Drug: Bevacizumab; 10 mg/kg intravenously every three weeks; Dietary supplement: Tocotrienol; Capsules, 300 mg orally three times daily
Experimental: Arm B: Continue treatment until progression	Drug: Bevacizumab; 10 mg/kg intravenously every three weeks; Dietary supplement: Tocotrienol; Capsules, 300 mg orally three times daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression free survival	6 months after enrollment of the last patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		12 months after enrollment of the last patient
Response rate as measured by RECIST 1.1 or CA-125		6 months after enrollment of the last patient
Safety as measured by CTC version 5.0	CTC = National Cancer Institute's Common Toxicity Criteria (NCI-CTC)	Every 9 weeks until progression, up to 3 years

Collaborators and Investigators

• Sponsor: Vejle Hospital
• Investigators: Study Chair: Torben F Hansen, MD, DMSc, Department of Oncology, Vejle Hospital - University Hospital of Southern Denmark

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2019
• Primary Completion (Actual): July 30, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: November 14, 2019
• First Submitted That Met QC Criteria: November 20, 2019
• First Posted (Actual): November 25, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 2, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Neoplasms by Histologic Type; Genital Diseases, Female; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Carcinoma; Carcinoma, Ovarian Epithelial; Recurrence; Ovarian Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Micronutrients; Antioxidants; Protective Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Vitamins; Bevacizumab; Vitamin E; Tocopherols; Tocotrienols
• Other Study ID Numbers: BeTo-Ovar

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No