Nivolumab + Bevacizumab + Rucaparib for Ovarian Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three drugs—Nivolumab (an immunotherapy drug), Bevacizumab (also known as Avastin, an anti-angiogenic drug), and Rucaparib (a PARP inhibitor)—to determine their effectiveness in treating ovarian, fallopian tube, or peritoneal cancer that has recurred after initial treatment. The goal is to assess whether this drug combination can slow or stop cancer growth. Suitable participants have previously undergone platinum-based chemotherapy, but their cancer returned despite that treatment. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people, providing an opportunity to contribute to significant findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using Nivolumab and Bevacizumab together is generally safe for patients with relapsed ovarian cancer. In one study, 89.5% of participants experienced at least one treatment-related side effect, but only 23.7% of these were severe. This indicates that while side effects are common, most are not serious.

Specific information about the combination of Nivolumab, Bevacizumab, and Rucaparib is limited. However, each drug is already used safely in other treatments. Past studies have demonstrated the safety of Nivolumab and Bevacizumab together, providing some confidence in adding Rucaparib, though further research would be beneficial.

These treatments are currently being tested in a phase 2 trial. This phase suggests some evidence of safety and tolerability, but additional research is needed for confirmation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for ovarian cancer because they offer a novel combination approach that targets the disease in multiple ways. Nivolumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. Bevacizumab, on the other hand, works by inhibiting blood vessel growth in tumors, essentially starving them. Rucaparib is a PARP inhibitor that prevents cancer cells from repairing themselves, leading to their death. This multi-faceted strategy could potentially be more effective than traditional options like surgery, chemotherapy, and single-drug therapies, offering new hope for patients with ovarian cancer.

What evidence suggests that this trial's treatments could be effective for relapsed ovarian cancer?

Research has shown that using Nivolumab and Bevacizumab together may help treat relapsed ovarian cancer. In one study, about 28.9% of women responded positively to this treatment combination. Bevacizumab is known to slow disease progression when used with other treatments. Rucaparib is already approved for certain ovarian cancer cases, particularly those with specific genetic changes. However, adding Nivolumab to Rucaparib did not significantly improve results in some cases. In this trial, participants will be assigned to different cohorts to study the effects of these combinations: one cohort will receive Nivolumab with Bevacizumab, while others will receive Nivolumab with Bevacizumab and Rucaparib. Each drug has potential, but their combined effectiveness for this condition remains under investigation. ^{1 2 6 7 8}

Who Is on the Research Team?

Joyce Liu, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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.

I rely on IV fluids or tube feeding for nutrition.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 (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]

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]

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]

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]

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]

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]

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 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]

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]

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