Comparing two doses of bevacizumab with chemotherapy for ovarian cancer

A Comparison of 2 Standard Doses of Bevacizumab in Combination With Chemotherapy in Epithelial Ovarian Cancer - a Pragmatic Trial

This study is testing whether a lower dose of the cancer drug bevacizumab works just as well as a higher dose when combined with chemotherapy for people with platinum-resistant ovarian cancer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 244 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: British Columbia Cancer Agency (other)
• Drugs / interventions: bevacizumab, chemotherapy, immunotherapy, Radiation
• Locations: 2 sites (Abbotsford British Columbia, British Columbia and 1 other locations)
• Trial ID: NCT04787289 on ClinicalTrials.gov

What this trial studies

This study compares two standard doses of the anti-cancer drug bevacizumab, 7.5 mg/kg and 15 mg/kg, in combination with chemotherapy for patients with platinum-resistant ovarian cancer. It is a pragmatic, two-arm, randomized trial involving 70 patients who will receive either dose every three weeks. The aim is to determine if the lower dose is non-inferior in terms of efficacy while potentially offering a better safety profile and reduced side effects. The study will also assess the duration of cancer control, side effect profiles, and quality of life between the two dosing regimens.

Who should consider this trial

Good fit: Ideal candidates are patients with histologically confirmed epithelial ovarian cancer who have platinum-resistant disease and measurable disease as defined by RECIST 1.1.

Not a fit: Patients with non-epithelial ovarian cancers or those who have not progressed on platinum-containing therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to safer and more cost-effective treatment options for patients with platinum-resistant ovarian cancer.

How similar studies have performed: Other studies have explored dosing strategies for bevacizumab, but this specific comparison of doses in platinum-resistant ovarian cancer is novel.

Eligibility criteria

Inclusion Criteria:

* Histologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal, or fallopian tube carcinoma according to WHO Classification of tumours that is advanced/metastatic/recurrent or unresectable and for which no curative therapy exists.
* Platinum resistant disease (progression within six months of completing a platinum-containing protocol). In this case, progression from the last line of therapy would be defined as radiologic progression by RECIST 1.1 criteria on CT or MR.
* Presence of clinically and/or radiologically documented disease. All radiology studies must be performed within 28 days of randomization.
* All patients must have measurable disease as defined by RECIST 1.1. The criteria for defining measurable disease are as follows:

  * Chest x-ray \> 20 mm
  * CT scan (with slice thickness of 5 mm) \> 10 mm longest diameter
  * Physical exam (using calipers) \> 10 mm Lymph nodes by CT scan \> 15 mm measured in short axis
* Patients must be \>= 18 years of age.
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
* Any number of prior lines of treatment is permitted. However, all patients must have received at least one prior regimen of chemotherapy including platinum. All patients may have received other therapies including immunotherapy, hormone therapy, or PARP inhibitors.
* Patients must have never received an anti-angiogenesis inhibitor including bevacizumab.
* A BC Cancer "Compassionate Access Program" (CAP) request must be approved prior to treatment
* Radiation: prior external beam radiation is permitted provided a minimum of 28 days (4 weeks) have elapsed between the last dose of radiation and date of treatment initiation. Exceptions may be made for low-dose, non-myelosuppressive radiotherapy after consultation with sponsor.
* Surgery: Previous surgery is permitted provided that a minimum of 28 days (4 weeks) have elapsed between any major surgery and date of randomization/registration, and that wound healing has occurred.
* Women of childbearing potential must have agreed to use a highly effective contraceptive method during the study and for up to 5 months after the last dose of chemotherapy/bevacizumab. A woman is considered to be of "childbearing potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgical sterility defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation, or vasectomy/vasectomized partner.
* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to any study specific procedures (see Section 6.0) to document their willingness to participate.

Patients who cannot give informed consent (i.e. mentally incompetent patients, or those physically incapacitated such as comatose patients) are not to be recruited into the study. Patients competent but physically unable to sign the consent form may have the document signed by their Legally Acceptable Representative (LAR) or legal guardian. Each patient will be provided with a full explanation of the study before consent is requested.

* Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits. Investigators must assure themselves the patients registered on this trial will be available for complete documentation of the treatment, response assessment, adverse events, and follow-up.

Exclusion Criteria:

* Patients with a history of other active or current malignancies that require active treatment.
* Patients with serious illness or medical conditions that might be aggravated by treatment or limit compliance including, but not limited to:

  * History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements.
  * Uncontrolled hypertension
  * Active uncontrolled or serious infection (viral, bacterial or fungal)
  * Other medical conditions that might be aggravated by study treatment
* Patients receiving concurrent treatment with other anti-cancer therapy or investigational agents.
* Neutrophils less than 1 x 10\^9 /L
* Pregnancy or breastfeeding
* Bleeding diathesis
* History of bowel obstruction or unresolved bowel obstruction (refer to the BC Cancer protocols above)
* Uncontrolled arterial or venous thromboembolism (note: once controlled, patient may still be eligible).
* Myocardial infarction (MI) or cerebrovascular accident (CVA) within 4 months.
* Untreated or uncontrolled central nervous system (CNS) metastatic disease.
* Open, non-healing wounds or known fistulas that have not healed.

Where this trial is running

Abbotsford British Columbia, British Columbia and 1 other locations

• Abbotsford Centre, BC Cancer Agency — Abbotsford British Columbia, British Columbia, Canada (RECRUITING)
• BC Cancer - Vancouver — Vancouver, British Columbia, Canada (RECRUITING)

Study contacts

• Principal investigator: Jenny Ko — BC Cancer
• Study coordinator: Jenny Ko

Conditions: Ovarian Cancer, Platinum-resistant Ovarian Cancer