Bevacizumab and Tocotrienol in Recurrent Ovarian Cancer

• ClinicalTrials.gov Identifier: NCT04175470
• Recruitment Status: Recruiting
• First Posted: November 25, 2019
• Last Update Posted: May 17, 2022
• Sponsor: Vejle Hospital
• Information provided by (Responsible Party): Vejle Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer Recurrent	Drug: Bevacizumab; Dietary Supplement: Tocotrienol	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Bevacizumab and Tocotrienol in Recurrent Ovarian Cancer: A Marker Based Phase II Trial
• Actual Study Start Date: October 29, 2019
• Estimated Primary Completion Date: May 2023
• Estimated Study Completion Date: August 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Progression free survival [ Time Frame: 6 months after enrollment of the last patient ]

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Louise Faaborg, MD; +45 7940 5446; louise.faaborg.larsen@rsyd.dk

Locations

Denmark

Department of Oncology, Vejle Hospital; Recruiting

Vejle, Denmark, 7100

Contact: Louise Faaborg, MD louise.faaborg.larsen@rsyd.dk

Sponsors and Collaborators

Vejle Hospital

Investigators

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

More Information

• Responsible Party: Vejle Hospital
• ClinicalTrials.gov Identifier: NCT04175470
• Other Study ID Numbers: BeTo-Ovar
• First Posted: November 25, 2019
• Last Update Posted: May 17, 2022
• Last Verified: May 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Recurrence; Disease Attributes; Pathologic Processes; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Tocotrienols; Vitamin E; Tocopherols; Bevacizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antioxidants; Molecular Mechanisms of Pharmacological Action