Nivolumab + Bevacizumab + Rucaparib for Ovarian Cancer

Recruiting at 2 trial locations

Overseen By DFCI Clinical Trials Hotline

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Immunosuppressants, PARP inhibitors

Disqualifiers: Platinum-refractory, Brain metastases, Cardiovascular diseases, Autoimmune diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 14

Duration: 2 years

73 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests three drugs for patients with relapsed ovarian, fallopian tube, or peritoneal cancer. Nivolumab helps the immune system fight cancer, Bevacizumab stops blood vessel growth, and Rucaparib blocks DNA repair in cancer cells. The goal is to find new treatment options for these patients. Bevacizumab has been approved for the treatment of advanced ovarian cancer and has shown effectiveness in prolonging survival in various studies.

Will I have to stop taking my current medications?

The trial requires participants to stop any hormonal therapy at least 1 week before starting treatment with nivolumab and bevacizumab, but hormone replacement therapy for post-menopausal symptoms can continue. Participants must also avoid natural herbal products or 'folk remedies' during the study.

What data supports the effectiveness of the drug combination Nivolumab, Bevacizumab, and Rucaparib for ovarian cancer?

Research shows that Bevacizumab, when combined with standard chemotherapy, improves progression-free survival in ovarian cancer patients, especially those at high risk of disease progression. Additionally, combining immunotherapy with anti-angiogenesis agents like Bevacizumab has shown improved outcomes in various cancers, suggesting potential benefits for ovarian cancer. ^{1 2 3 4 5}

Is the combination of Nivolumab, Bevacizumab, and Rucaparib generally safe for humans?

Bevacizumab, one of the drugs in the combination, has been approved for use in ovarian cancer and has been studied in several clinical trials, showing expected types and frequencies of side effects. Rucaparib is also approved for ovarian cancer, but specific safety data for the combination with Nivolumab is not detailed in the available research. ^{6 7 8 9 10}

How does the drug combination of Nivolumab, Bevacizumab, and Rucaparib for ovarian cancer differ from other treatments?

This drug combination is unique because it combines Nivolumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with Bevacizumab, which inhibits blood vessel growth in tumors, and Rucaparib, a PARP inhibitor that targets cancer cell DNA repair mechanisms. This multi-faceted approach is different from standard treatments that typically focus on chemotherapy or single-agent therapies. ^{2 3 11 12 13}

Research Team

Joyce Liu, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults over 18 with relapsed ovarian, fallopian tube, or peritoneal cancer who've had standard therapy and up to 3 chemo regimens. They must not be pregnant, breastfeeding, have certain allergies or infections, uncontrolled illnesses, recent surgeries or severe psychiatric conditions. Participants need measurable disease by RECIST criteria and agree to use contraception.

Inclusion Criteria

My cancer returned more than 6 months after platinum chemotherapy, or within 6-12 months but not within 2 months.

I am using certain approved corticosteroids.

I have been tested for BRCA mutations and do not have harmful changes.

Exclusion Criteria

I have not had major surgery or a serious injury in the last 28 days.

I have never taken PARP inhibitors before.

Any patient with a history of major depressive episode, bipolar disorder, obsessive/compulsive disorder, schizophrenia, a history of suicide attempt or ideation, or homicide/homicidal ideation as judged by the investigator and/or based on recent psychiatric assessment may not participate in this study without discussion with and agreement of the study PI.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nivolumab, Bevacizumab, and Rucaparib every 14 days, with Rucaparib taken orally twice daily on days 1-14

2 years

Visits every 14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Bevacizumab
• Nivolumab
• Rucaparib

Trial Overview The study tests a combination of Nivolumab (an immune system booster), Bevacizumab (a blood vessel growth inhibitor), and Rucaparib (a DNA repair blocker) in patients with specific types of relapsed cancers. It aims to evaluate the safety and effectiveness of this drug trio.

Participant Groups

Group I: Cohort 3: Nivolumab with Bevacizumab and Rucaparib Experimental Treatment 3 Interventions

Patients will receive treatment every 14 days with Nivolumab, Bevacizumab administered on day 1 of each cycle and Rucaparib will be taken orally twice daily on days 1-14 .

Group II: Cohort 2: Nivolumab with Bevacizumab and Rucaparib Experimental Treatment 3 Interventions

Patients will receive treatment every 14 days with Nivolumab, Bevacizumab administered on day 1 of each cycle and Rucaparib will be taken orally twice daily on days 1-14 .

Group III: Cohort 1: Nivolumab with Bevacizumab Experimental Treatment 2 Interventions

Patients will receive treatment every 14 days with Nivolumab and Bevacizumab administered on day 1 of each cycle.

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Clovis Oncology, Inc.

Industry Sponsor

Trials

65

Recruited

11,100+

Patrick J. Mahaffy

Clovis Oncology, Inc.

Chief Executive Officer since 2009

BA from Haverford College, MBA from Columbia University

Lindsey Rolfe

Clovis Oncology, Inc.

Chief Medical Officer since 2015

Specialist accreditation in pharmaceutical medicine

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

Bevacizumab (Avastin) has been approved for use in combination with other therapies for patients with platinum-resistant ovarian cancer, showing antitumor activity in this challenging setting.

Despite the overall low response rates (around 10%) to treatments for platinum-resistant ovarian cancer, bevacizumab is currently the most studied antiangiogenic therapy, with ongoing research into alternative treatments like tyrosine kinase inhibitors and angiopoietin inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of bevacizumab in the treatment of platinum-resistant ovarian cancer: current perspectives. McClung, EC., Wenham, RM.[2022]

Bevacizumab has been shown to be effective in managing epithelial ovarian cancer, particularly when combined with cytotoxic chemotherapy, as indicated by phase III trial data that demonstrate improved progression-free survival.

There is a compelling argument for using bevacizumab as a single agent in patients with platinum-resistant ovarian cancer, suggesting a more rational and potentially cost-effective approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of bevacizumab in the management of ovarian cancer: an argument for single-agent rather than combination therapy. Markman, M.[2020]

The IMagyn050/GOG 3015/ENGOT-OV39 trial is a significant phase III study involving 1300 patients with advanced epithelial ovarian cancer, testing the efficacy of atezolizumab combined with standard chemotherapy and bevacizumab against a placebo.

The primary goal is to determine if this combination therapy can improve progression-free survival and overall survival, particularly in patients with PD-L1+ tumors, potentially leading to better treatment outcomes for ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trials in progress: IMagyn050/GOG 3015/ENGOT-OV39. A Phase III, multicenter, randomized study of atezolizumab versus placebo administered in combination with paclitaxel, carboplatin, and bevacizumab to patients with newly-diagnosed stage III or stage IV ovarian, fallopian tube, or primary peritoneal cancer. Moore, KN., Pignata, S.[2022]

In a study of 299 patients with advanced ovarian cancer, combining bevacizumab with carboplatin/paclitaxel resulted in a median progression-free survival of 15.4 months, indicating its efficacy as a front-line treatment.

The treatment was generally safe, with 54% of patients experiencing grade 3/4 adverse events, primarily hypertension and neutropenia, and a 1-year overall survival rate of 94%, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of front-line bevacizumab in advanced ovarian cancer: the OSCAR study. Hall, M., Bertelli, G., Li, L., et al.[2020]

Bevacizumab, an antiangiogenesis drug, has been approved by the US FDA for use in combination with chemotherapy for women with newly diagnosed ovarian cancer, based on a Phase III clinical trial that demonstrated improved progression-free survival.

The approval extends to both frontline and maintenance therapy for different types of ovarian cancer, including platinum-sensitive and platinum-resistant recurrent cases, highlighting its versatility in treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab use in the frontline, maintenance and recurrent settings for ovarian cancer. Haunschild, CE., Tewari, KS.[2023]

Recent advancements in ovarian cancer treatment have introduced several new options that show improved survival rates compared to historical data, marking a significant progress after decades of stagnation.

Three new PARP inhibitors (olaparib, rucaparib, niraparib) have been approved for ovarian cancer, providing new maintenance and recurrence treatment options, alongside expanded uses for bevacizumab in combination chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Therapies for Ovarian Cancer. O'Malley, DM.[2020]

In a study of 46 patients with advanced and recurrent epithelial ovarian cancer treated with bevacizumab and chemotherapy over 30 months, the most common adverse events were hypertension (65.2%) and proteinuria (49%), with hypertension typically occurring 2 months after treatment initiation.

Patients with a history of radiation therapy experienced a significantly higher risk of gastrointestinal perforation, indicating that careful consideration is needed when administering bevacizumab to these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Associated With Long-term Treatment of Epithelial Ovarian Cancer With Bevacizumab and Chemotherapy. Yokoyama, Y., Kubo-Kaneda, M., Sunada, K., et al.[2022]

Bevacizumab, an anti-angiogenic agent, has been approved for use in advanced ovarian cancer and has shown significant efficacy when combined with standard chemotherapy in multiple phase III trials involving women with ovarian cancer.

While bevacizumab's safety profile aligns with expectations, ongoing research is necessary to identify markers that can predict patient response to optimize treatment outcomes, and new anti-angiogenic agents are currently being evaluated in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in combination with chemotherapy for the treatment of advanced ovarian cancer: a systematic review. Aravantinos, G., Pectasides, D.[2023]

In a phase Ib study involving 20 patients with platinum-resistant ovarian cancer, the combination of atezolizumab and bevacizumab demonstrated a safety profile consistent with the individual drugs, with 95% experiencing treatment-related adverse events, but no grade 5 events reported.

The treatment resulted in a 15% overall response rate, with some patients achieving durable responses lasting up to 18.9 months, and a disease control rate of 55%, indicating potential efficacy in managing this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Clinical Activity of Atezolizumab Plus Bevacizumab in Patients with Ovarian Cancer: A Phase Ib Study. Moroney, JW., Powderly, J., Lieu, CH., et al.[2021]

A 77-year-old woman with platinum-resistant recurrent ovarian cancer achieved long-term disease control for 29 months using a combination therapy of bevacizumab and gemcitabine (BEV + GEM).

This case highlights the potential of BEV + GEM to significantly prolong survival in patients with difficult-to-treat ovarian cancer, marking it as a promising treatment option in this challenging scenario.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum-resistant recurrent ovarian cancer with long survival on bevacizumab and gemcitabine. Komiyama, S., Kugimiya, T., Takeya, C., et al.[2022]

Bevacizumab, when combined with carboplatin and paclitaxel, significantly prolongs progression-free survival in women with newly diagnosed advanced ovarian cancer, as shown in the GOG-0218 and ICON7 studies.

In patients with recurrent platinum-sensitive ovarian cancer, bevacizumab combined with carboplatin and gemcitabine also extends progression-free survival, demonstrating its efficacy in both first-line and second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab combination therapy: a review of its use in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Dhillon, S.[2019]

In a phase 3 trial involving 682 patients with recurrent ovarian cancer, the combination of carboplatin-pegylated liposomal doxorubicin and bevacizumab showed a median progression-free survival of 13.3 months, significantly longer than the 11.6 months observed with the standard carboplatin-gemcitabine-bevacizumab regimen (p=0.012).

The safety profile was comparable between the two treatment groups, with hypertension and neutropenia being the most common severe adverse events; however, treatment-related deaths were rare, occurring in less than 1% of patients in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Pfisterer, J., Shannon, CM., Baumann, K., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Profile of bevacizumab in the treatment of platinum-resistant ovarian cancer: current perspectives. [2022]

3. England pubmed.ncbi.nlm.nih.gov

The use of bevacizumab in the management of ovarian cancer: an argument for single-agent rather than combination therapy. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Trials in progress: IMagyn050/GOG 3015/ENGOT-OV39. A Phase III, multicenter, randomized study of atezolizumab versus placebo administered in combination with paclitaxel, carboplatin, and bevacizumab to patients with newly-diagnosed stage III or stage IV ovarian, fallopian tube, or primary peritoneal cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Role of front-line bevacizumab in advanced ovarian cancer: the OSCAR study. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Bevacizumab use in the frontline, maintenance and recurrent settings for ovarian cancer. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

New Therapies for Ovarian Cancer. [2020]

8. Greece pubmed.ncbi.nlm.nih.gov

Adverse Events Associated With Long-term Treatment of Epithelial Ovarian Cancer With Bevacizumab and Chemotherapy. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Bevacizumab in combination with chemotherapy for the treatment of advanced ovarian cancer: a systematic review. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Safety and Clinical Activity of Atezolizumab Plus Bevacizumab in Patients with Ovarian Cancer: A Phase Ib Study. [2021]

11. Australia pubmed.ncbi.nlm.nih.gov

Platinum-resistant recurrent ovarian cancer with long survival on bevacizumab and gemcitabine. [2022]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Bevacizumab combination therapy: a review of its use in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. [2022]