Using Olaparib and Bevacizumab for First Line Treatment in HRD Positive Ovarian Cancer

A Phase IV Trial to Confirm the Efficacy of Olaparib in Combination With Bevacizumab as Frontline Treatment of HRD Positive Ovarian Tumors

This study is testing if a combination of two drugs, olaparib and bevacizumab, can help people with advanced ovarian cancer who have a specific genetic marker feel better after their initial treatment.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 190 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Mario Negri Institute for Pharmacological Research (Academic / other)
• Drugs / interventions: bevacizumab, chemotherapy
• Locations: 2 sites (San Fermo Della Battaglia, Como and 1 other locations)
• Trial ID: NCT06121401 on ClinicalTrials.gov

What this trial studies

This phase IV clinical trial aims to evaluate the effectiveness of olaparib in combination with bevacizumab as a maintenance treatment for patients with advanced high-grade epithelial ovarian cancer who are HRD-positive. The study will assess the proportion of patients responding to this treatment after completing first-line chemotherapy. Additionally, it includes two translational research projects: one analyzing circulating-tumor DNA through liquid biopsies to monitor disease evolution, and another generating organotypic models to predict treatment response in cancer stem cells. The trial is designed to reflect real-world clinical practice.

Who should consider this trial

Good fit: Ideal candidates are patients with advanced high-grade epithelial ovarian cancer who are HRD-positive and have completed first-line chemotherapy with bevacizumab.

Not a fit: Patients who have not received prior treatment with bevacizumab or those with non-HRD-positive tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could improve outcomes for patients with advanced ovarian cancer by providing a more effective maintenance therapy.

How similar studies have performed: Previous studies have shown promising results with similar combinations of PARP inhibitors and anti-angiogenic agents, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Patient who has completed first line platinum-taxane chemotherapy
2. Patient on treatment with bevacizumab (patient must have received at least 1 cycle of bevacizumab in combination with chemotherapy). Bevacizumab treatment should have been administered at a dose of 15mg/kg q3 weeks.
3. Patient must be without evidence of disease (NED) or in complete response (CR) or partial response (PR) from her first line treatment.
4. Patients with histologically confirmed high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer and HRD-positive tumor according to the Myriad Mychoice CDx Plus evaluation.
5. Patients must have normal organ and bone marrow function values measured within 28 days before administration of olaparib
6. Normal blood pressure (BP) or adequately treated and controlled hypertension (systolic BP ≤ 140 mmHg and/or diastolic BP ≤ 90 mmHg

8. Patients must have a life expectancy ≥ 16 weeks. 9. Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of olaparib administration and confirmed the day of treatment start.

Exclusion Criteria:

1. Persistent toxicities (Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia
2. Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
3. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required
4. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
5. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
6. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
7. Patients with known active hepatitis (i.e. Hepatitis B or C).
8. Any previous treatment with PARP inhibitor, including Olaparib.
9. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to olaparib.
10. Major surgery within 2 weeks of starting olaparib and patients must have recovered from any effects of any major surgery
11. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy is permitted as are steroidal antiemetics).
12. Concomitant use of known strong CYP3A inhibitors
13. Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers
14. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
15. Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
16. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of olaparib or puts the patient at high risk for treatment-related complications.
17. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
18. Breast feeding and pregnant women

Where this trial is running

San Fermo Della Battaglia, Como and 1 other locations

• Azienda Socio Sanitaria Territoriale (ASST) Lariana — San Fermo Della Battaglia, Como, Italy (Recruiting)
• Istituto Oncologico Veneto IRCCS — Padova, Italy (Recruiting)

Study contacts

• Principal investigator: Federica Tomao — Università degli Studi di Roma "La Sapienza", Viale del Policlinico 155, Roma
• Study coordinator: Elena Biagioli

Conditions Carcinoma, Ovarian Epithelial