Bevacizumab + Niraparib for Ovarian and Endometrial Cancer

(ARID1A Trial)

No longer recruiting at 2 trial locations

Overseen By SCC IIT Office

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Oklahoma

Must not be taking: PARP inhibitors

Disqualifiers: Uncontrolled hypertension, Brain metastases, 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: 3

Duration: As long as the tumor is not growing or spreading and no unacceptable side effects occur

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, bevacizumab (Avastin) and niraparib (Zejula), to evaluate their effectiveness in treating ovarian or endometrial cancer that has recurred with a specific ARID1A mutation. Researchers aim to determine if these drugs can shrink tumors and assess the treatment's benefits and side effects. Women whose cancer has returned after treatment and who have the ARID1A mutation might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research shows that the combination of niraparib and bevacizumab has been studied for safety in treating ovarian cancer. Previous studies found that patients generally tolerated this combination well. The safety profile of using these drugs together aligned with existing knowledge, meaning any side effects were expected and manageable.

Patients experienced some side effects with this combination, such as high blood pressure, tiredness, or nausea. However, these effects are common with many cancer treatments. While these side effects can be uncomfortable, healthcare teams can often help manage them.

Overall, both niraparib and bevacizumab have been used safely in cancer treatment before. Discussing possible side effects with a doctor can help prospective trial participants understand how this treatment might fit into their plan. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for ovarian and endometrial cancer typically involve chemotherapy and surgery. But researchers are excited about Bevacizumab and Niraparib because they offer a targeted approach. Niraparib is a PARP inhibitor that interferes with cancer cell repair mechanisms, potentially leading to cancer cell death, and it's taken orally, making it more convenient. Bevacizumab, on the other hand, is a monoclonal antibody that inhibits the growth of blood vessels that supply tumors, administered intravenously. This combination could enhance effectiveness by attacking cancer in two different ways, potentially leading to better outcomes.

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

This trial will compare the effectiveness of Niraparib alone versus the combination of Niraparib and Bevacizumab for treating advanced ovarian and endometrial cancer. Studies have shown that using Niraparib and Bevacizumab together can help treat advanced ovarian cancer. Research indicates that this combination helps patients live longer without their cancer worsening. In one study, patients taking both Niraparib and Bevacizumab lived for 29.4 months, compared to 27.8 months for those taking only Niraparib. Additionally, this combination has shown promising results in delaying cancer progression. The safety of this combination aligns with existing knowledge about these drugs. ^{1 2 4 5 6}

Who Is on the Research Team?

Lauren Dockery, MD

Principal Investigator

Stephenson Cancer Center

Are You a Good Fit for This Trial?

This trial is for women over 18 with recurrent endometrial or ovarian cancer and ARID1A mutation. They must not be pregnant, have a life expectancy over 12 weeks, and able to take oral medication. Participants need measurable disease by RECIST v1.1, good organ function, ECOG ≤ 1, and recovery from major surgery without open wounds.

Inclusion Criteria

You are expected to live for more than 12 weeks.

I am fully active and can carry on all my pre-disease activities without restriction.

Patient is willing and able to comply with the protocol for the duration of the study

Exclusion Criteria

My cancer is advanced but localized, and can potentially be cured.

I have never been treated with a PARP inhibitor, including niraparib.

Patients with a known hypersensitivity to investigational drugs or excipients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive niraparib alone or in combination with bevacizumab, with monitoring for tumor response and side effects

As long as the tumor is not growing or spreading and no unacceptable side effects occur

Niraparib daily, Bevacizumab every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Niraparib

Trial Overview The study tests the tumor response to niraparib combined with bevacizumab in patients with specific recurrent cancers. It aims to understand the effectiveness and side effects of this treatment combination in those who've had prior platinum-based therapy.

How Is the Trial Designed?

Group I: Arm 2: Niraparib and Bevacizumab Experimental Treatment 2 Interventions

Niraparib (200mg or 300 mg based on body weight and blood platelet count), oral, once daily. Bevacizumab (15 mg/kg, IV on day 1 of each cycle).

Group II: Arm 1: Niraparib Active Control 1 Intervention

Niraparib (200mg or 300 mg based on body weight and blood platelet count), oral, once daily.

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?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

University of Virginia

Collaborator

Trials

802

Recruited

1,342,000+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

In a study involving patients with newly diagnosed advanced ovarian cancer, the combination of olaparib and bevacizumab significantly improved overall survival (OS) in patients with homologous recombination deficiency (HRD), showing a 5-year OS rate of 65.5% compared to 48.4% for those receiving placebo.

The safety profile of olaparib plus bevacizumab was favorable, with low and balanced incidences of serious conditions like myelodysplastic syndrome and acute myeloid leukemia between treatment groups, confirming its potential as a standard care option for HRD-positive ovarian cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Ray-Coquard, I., Leary, A., Pignata, S., et al.[2023]

Niraparib significantly improves progression-free survival and other key outcomes in patients with recurrent, platinum-sensitive ovarian cancer, based on the phase III NOVA trial involving a randomized, double-blind, placebo-controlled design.

The treatment has a manageable safety profile, with most serious side effects being blood-related issues, which can be effectively managed through dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib: A Review in Ovarian Cancer. Heo, YA., Duggan, ST.[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]

Niraparib significantly improves progression-free survival in patients with recurrent ovarian, fallopian tube, and primary peritoneal cancers, showing 21 months for gBRCA mutation carriers and 9.3 months for non-gBRCA patients compared to much shorter durations with placebo.

As a PARP inhibitor, niraparib works by blocking a key DNA repair mechanism in cancer cells, making it an effective maintenance therapy for patients who have responded to platinum-based treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib for the Treatment of Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. Kerliu, L., Myruski, S., Bhatti, A., et al.[2020]

In a study of 105 patients with newly diagnosed advanced ovarian cancer, the combination of niraparib and bevacizumab as first-line maintenance therapy resulted in a promising progression-free survival (PFS) rate of 62% at 18 months, with even higher rates in patients with homologous recombination deficiency (76%).

The safety profile of this combination therapy was consistent with the known side effects of the individual drugs, with common treatment-related adverse events including thrombocytopenia, fatigue, and anemia, indicating that the treatment is manageable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab. Hardesty, MM., Krivak, TC., Wright, GS., et al.[2022]

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 15 heavily pre-treated ovarian cancer patients, bevacizumab demonstrated a tolerable safety profile, with no gastrointestinal perforations observed, which is a significant concern in previous studies.

The treatment resulted in a partial response in 13.3% of patients and stable disease in 40%, with a median overall survival of 15 months, suggesting that bevacizumab may be an effective option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in heavily pre-treated and platinum resistant ovarian cancer: a retrospective study of the North-Eastern German Society of Gynaecologic Oncology (NOGGO) Ovarian Cancer Study Group. Pietzner, K., Richter, R., Chekerov, R., et al.[2022]

Niraparib, a recently approved treatment for recurrent platinum-sensitive ovarian cancer, has demonstrated a high oral bioavailability of 72.7% in humans, indicating effective absorption when taken orally.

The study involved six patients who received a therapeutic dose of 300 mg of niraparib, followed by a small intravenous dose to measure its levels in the bloodstream, confirming its potential as a convenient oral treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients. van Andel, L., Rosing, H., Zhang, Z., et al.[2019]

Bevacizumab, an anti-VEGF therapy, has shown efficacy in treating epithelial ovarian cancers, both as a standalone treatment and in combination with other therapies, based on evidence from Phase II trials involving various patient populations.

While most side effects of bevacizumab, such as proteinuria and hypertension, are mild and manageable, there are serious but rare risks like arterial thromboembolism and gastrointestinal perforation, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with bevacizumab in the management of epithelial ovarian cancer. Burger, RA.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05523440

NCT05523440 | Bevacizumab and/or Niraparib in Patients ... The purpose of this research study is to test the proportion of tumor response to the combination treatment with niraparib and bevacizumab and see what ...

2. ascopubs.org ascopubs.org/doi/10.1200/PO.23.00693

Findings From Cohort A of the OPAL Phase II Trial Results demonstrated modest activity of niraparib, dostarlimab, and bevacizumab in participants with PROC, many of whom had prognostic factors for poor ...

3. oncpracticemanagement.com oncpracticemanagement.com/web-exclusive-articles/chemotherapy-free-parp-inhibitor-combination-improves-outcomes-versus-single-agent-parp-inhibitor-in-recurrent-ovarian-cancer

Chemotherapy-Free PARP Inhibitor Combination Improves ... Overall survival with 52% event maturity was 29.4 months with the niraparib plus bevacizumab combination compared with 27.8 months with single-agent niraparib ( ...

4. onclive.com onclive.com/view/frontline-maintenance-with-niraparib-plus-bevacizumab-is-active-in-advanced-ovarian-cancer

Frontline Maintenance With Niraparib Plus Bevacizumab ... Niraparib and bevacizumab combination therapy showed durable overall survival in advanced ovarian cancer without affecting health-related ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35690498/

OVARIO phase II trial of combination niraparib plus ... Conclusion: Niraparib + bevacizumab first-line maintenance therapy displayed promising PFS results. Safety was consistent with the known safety ...

6. cancernetwork.com cancernetwork.com/view/data-support-niraparib-combo-as-first-line-maintenance-in-ovarian-cancer

Data Support Niraparib Combo as First-Line Maintenance ... Niraparib plus bevacizumab would provide the biggest benefit in the first-line maintenance setting for patients with advanced ovarian cancer.