Olaparib +/- Bevacizumab for Ovarian Cancer

Recruiting at 636 trial locations

Overseen By Ying Liu, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: NRG Oncology

Must be taking: Platinum-based chemotherapy

Must not be taking: PARP inhibitors

Disqualifiers: Pregnancy, Cardiac disease, Infection, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 24

Duration: 1-2 years

880 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of the drug olaparib when taken for one year versus two years, with or without the addition of bevacizumab, in treating advanced ovarian cancer. Olaparib may prevent cancer cell growth by blocking certain enzymes, while bevacizumab cuts off the blood supply tumors need to grow. The trial targets individuals with stage III or IV ovarian cancer who have specific genetic changes, such as BRCA mutations. It suits those who have completed initial chemotherapy and currently show no signs of cancer progression. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to advancing treatment options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use strong or moderate CYP3A inducers (a type of drug that affects how your body processes certain medications). It's best to discuss your current medications with the trial team.

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

Research has shown that using olaparib with bevacizumab is generally safe. In a study with older patients, this treatment did not significantly change their quality of life, indicating it was well-tolerated. Another study found that adding olaparib to bevacizumab helped patients live longer without their cancer returning. Although all treatments can have side effects, evidence suggests this combination is usually safe for patients with advanced ovarian cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about olaparib and bevacizumab for ovarian cancer because they work in a novel way compared to traditional chemotherapy options. Olaparib is a PARP inhibitor, which means it targets and disrupts cancer cells' ability to repair their DNA, potentially leading to their death. Bevacizumab complements this by blocking the blood vessels tumors need to grow, cutting off their nutrient supply. Together, they offer a targeted approach that could enhance effectiveness and reduce reliance on broad-spectrum chemotherapy, which often comes with significant side effects.

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

Research has shown that using olaparib with bevacizumab may effectively treat advanced ovarian cancer, particularly in patients with specific genetic traits like BRCA mutations or HRD (a type of DNA repair issue). This trial will evaluate the combination of olaparib and bevacizumab. Studies have found that this combination helps patients live longer without their cancer worsening compared to using bevacizumab alone. Specifically, one study revealed that 67% of patients taking both drugs did not see their cancer grow or return, while only 30% of those taking bevacizumab with a placebo experienced the same result. Additionally, this combination has been linked to a significant improvement in overall survival for patients with HRD, reducing the risk of death by 38%. This demonstrates its potential as an effective treatment for advanced ovarian cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Ying Liu

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for patients with advanced ovarian cancer (stages III or IV) that's BRCA 1/2 mutated or homologous recombination deficient. Participants must have completed 4-9 cycles of platinum-based chemotherapy and undergone surgery to remove the tumor. They can't join if they've had certain treatments that could interfere with the study.

Inclusion Criteria

My cancer is high grade serous.

My cancer is high grade endometrioid or ovarian with a harmful BRCA mutation.

I have a BRCA1 or BRCA2 gene mutation linked to cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olaparib for 1 or 2 years, with optional bevacizumab for up to 1 year

1-2 years

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 2 years, then every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Olaparib

Trial Overview The trial is testing how long to give Olaparib, a drug that blocks enzymes tumors need to grow, either one year or two years, and whether adding Bevacizumab, which stops blood vessel growth in tumors, makes a difference in treatment effectiveness.

How Is the Trial Designed?

Group I: Arm II (olaparib, bevacizumab) Experimental Treatment 5 Interventions

Patients receive olaparib PO BID on days 1-21 of each cycle. Cycles repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients may also receive bevacizumab IV on day 1 of each cycle. Cycles of bevacizumab repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT and/or MRI throughout the study.

Group II: Arm I (olaparib, bevacizumab) Active Control 5 Interventions

Patients receive olaparib PO BID on days 1-21 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may also receive bevacizumab IV on day 1 of each cycle. Cycles of bevacizumab repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT and/or MRI throughout the study.

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9596645/

Cost-Effectiveness Analysis of Olaparib in Combination ... Maintenance therapy with olaparib plus bevacizumab demonstrated a clinically significant benefit in PFS compared with bevacizumab monotherapy in ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1911361

Olaparib plus Bevacizumab as First-Line Maintenance in ... Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation.

3. lynparza.com lynparza.com/ovarian-cancer/results/advanced-ovarian-cancer.html

Results of LYNPARZA: advanced ovarian cancer 168 out of 255 patients on LYNPARZA + bevacizumab did not see their cancer grow or return compared with 40 out of 132 patients on bevacizumab + placebo. 67%.

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)00686-5/fulltext

final overall survival results from the PAOLA-1/ENGOT ... Conclusions. Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer.

5. merck.com merck.com/news/lynparza-olaparib-in-combination-with-bevacizumab-and-as-monotherapy-demonstrates-clinically-meaningful-long-term-survival-in-certain-patients-with-first-line-advanced-ovarian-cancer-in-expl/

LYNPARZA® (olaparib) in Combination With ... - Merck.com These latest results at the five-year landmark demonstrate that olaparib with bevacizumab reduces the risk of death by 38% in HRD-positive ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39673779

Safety and quality of life with maintenance olaparib plus ... Conclusion: Among older patients in PAOLA-1, olaparib plus bevacizumab had a manageable safety profile and no adverse impact on QoL. Additional ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0959804922017798

Efficacy and safety of maintenance olaparib ... The phase III PAOLA-1/ENGOT-ov25 study (NCT02477644) showed that addition of olaparib to bevacizumab maintenance improved progression-free survival (PFS) in ...

8. academic.oup.com academic.oup.com/oncolo/article/30/7/oyae322/7924129

Safety and quality of life with maintenance olaparib plus ... Among older patients in PAOLA-1, olaparib plus bevacizumab had a manageable safety profile and no adverse impact on QoL. Additional data are ...