Clinical trial NCT04175470: Bevacizumab and Tocotrienol in Recurrent Ovarian Cancer
Official title: Bevacizumab and Tocotrienol in Recurrent Ovarian Cancer: A Marker Based Phase II Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer Recurrent
Lead sponsor: Vejle Hospital
Sponsor class: OTHER
First posted: 2019-11-25
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Progression free survival
timeFrame: 6 months after enrollment of the last patient
Secondary outcomes:
measure: Overall survival
timeFrame: 12 months after enrollment of the last patient
measure: Response rate as measured by RECIST 1.1 or CA-125
timeFrame: 6 months after enrollment of the last patient
measure: Safety as measured by CTC version 5.0
timeFrame: Every 9 weeks until progression, up to 3 years
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, DMSc
role: STUDY_CHAIR
References: