Combination Therapy for Ovarian Cancer

(OPAL Trial)

No longer recruiting at 34 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Tesaro, Inc.

Must not be taking: Steroids, Immunosuppressants, Live vaccines

Disqualifiers: Immunodeficiency, Uncontrolled 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 15 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well the drug niraparib (also known as Zejula) works with other treatments for ovarian, fallopian tube, or primary peritoneal cancer. The researchers aim to determine the effectiveness and safety of these combinations for individuals with recurrent or newly diagnosed cancer. Those with recurrent ovarian cancer who have tried 1-2 other treatments, or those with newly diagnosed advanced-stage ovarian cancer, might be suitable candidates for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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

The trial requires a washout period (time without taking certain medications) of 3 weeks for any prior systemic anticancer therapy before starting the study treatment. This means you may need to stop some medications, but the protocol does not specify all medications that must be stopped. It's best to discuss your current medications with the study team to get specific guidance.

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

Research shows that the combination of TSR-042, bevacizumab, and niraparib has demonstrated positive effects in treating ovarian cancer. Studies have assessed the safety of these treatments when used together. Reports suggest that most people tolerate these drugs well, although some may experience side effects, which can vary from person to person.

For niraparib, whether used alone or with other treatments, research suggests it is generally well-tolerated, especially if doses are adjusted early on if needed. Common side effects might include fatigue or nausea, but proper care can manage these. Trials have shown that niraparib helps control ovarian cancer and is already approved for use in some situations.

Prospective trial participants should discuss any concerns with their healthcare provider. ^{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 explore innovative combinations and strategies to tackle this challenging disease. Unlike the standard platinum-taxane chemotherapy, these trials incorporate Niraparib, a PARP inhibitor, which targets cancer cells with specific genetic weaknesses, potentially enhancing treatment effectiveness. Additionally, TSR-042 (Dostarlimab) is being tested alongside Bevacizumab and Niraparib in PARP inhibitor-naive patients, offering a fresh approach by engaging the immune system to combat cancer. These combinations aim to improve outcomes by personalizing therapy based on individual tumor characteristics, providing hope for better management of ovarian cancer.

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

Research has shown that the combination of TSR-042, bevacizumab, and niraparib, which participants in Cohort A of this trial may receive, can help treat ovarian cancer, even in patients with challenging conditions. This combination might slow the disease in some cases.

In Cohort C, Arm 2 of this trial, niraparib is administered before the main treatment. Studies have shown encouraging results, with 62.5% of patients experiencing a reduction in cancer size and 87.5% achieving some level of disease control. Additionally, using niraparib as a follow-up treatment has significantly extended the time patients remain without cancer progression.

Overall, these treatments have shown potential benefits in managing ovarian cancer, especially for those with specific genetic profiles. ^{5 6 7 8 9}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

This trial is for women aged 18 or older with high-grade recurrent ovarian, fallopian tube, or primary peritoneal cancer. They must have measurable disease and be in good enough health to participate (ECOG status of 0-2). Pregnant or breastfeeding women can't join, and participants need adequate organ function and not be on certain medications.

Inclusion Criteria

My white blood cell count is healthy without needing medication.

Participant is not pregnant or breastfeeding and meets the specified conditions

Additional requirements for pregnancy testing during and after study treatment as per protocol

Exclusion Criteria

Participants specific to Cohort C must meet additional exclusion criteria as specified

I had cancer treatment within the last 3 weeks.

I have uncontrolled cancer spread to my brain or its coverings causing symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Screening

Participants receive a run-in cycle of carboplatin-paclitaxel to confirm HRd status

Up to 5 weeks

Treatment

Participants receive treatment with TSR-042, Bevacizumab, and Niraparib or platinum-taxane doublet chemotherapy

Up to 15 months

Maintenance

Participants receive maintenance treatment with Niraparib and optional Bevacizumab

Until progression or toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Carboplatin
• Niraparib
• Paclitaxel
• TSR-042

Trial Overview The study tests the effectiveness and safety of niraparib alone or combined with other treatments like TSR-042, Bevacizumab, Paclitaxel, Carboplatin in treating ovarian cancer. Cohort A focuses on those with recurrent cancer; Cohort C includes newly diagnosed patients.

How Is the Trial Designed?

Group I: Cohort C: Arm 2: Participants receiving neoadjuvant Niraparib Experimental Treatment 2 Interventions

Participants are expected to receive 1 run-in cycle (up to 5 weeks) of carboplatin-paclitaxel during pre-screening. After confirmation that the tumor is HRd, participants will be randomized to three 21-day cycles of neoadjuvant niraparib therapy. After IDS, all participants will receive up to three 21-day cycles of adjuvant platinum-taxane doublet chemotherapy (and optional bevacizumab for participants deemed high-risk; third cycle is optional) followed by niraparib (and optional bevacizumab or bevacizumab biosimilar for participants deemed high- risk) maintenance treatment.

Group II: Cohort A: 1-2 prior lines of therapy (TSR-042, Bevacizumab, and Niraparib) Experimental Treatment 3 Interventions

PARP Inhibitor-Naive Platinum-Resistant Ovarian Cancer Treatment Cohort with TSR-042, Bevacizumab, and Niraparib. TSR-042 administered 500 milligrams (mg) on Day 1 every 3 weeks (Q3W) for 4 cycles (each cycle is 21 days), followed by 1000 mg every 6 weeks (Q6W) beginning on Cycle 5 Day 1 until progressive disease (PD) or toxicity. Bevacizumab administered 15 milligram per kilogram (mg/kg) every 3 weeks for up to 15 months. Niraparib 200 or 300 mg per day until PD or toxicity.

Group III: Cohort C: Arm 1: Participants receiving platinum plus taxane Active Control 4 Interventions

Participants are expected to receive 1 run-in cycle (up to 5 weeks) of carboplatin-paclitaxel during pre-screening. After confirmation that the tumor is homologous recombination-deficient (HRd). Participants will then be randomized to three 21-day cycles of platinum-taxane doublet chemotherapy (carboplatin plus paclitaxane). After interval debulking surgery (IDS), all participants will receive up to three 21-day cycles of adjuvant platinum-taxane doublet chemotherapy (and optional bevacizumab for participants deemed high-risk; third cycle is optional) followed by niraparib (and optional bevacizumab or bevacizumab biosimilar for participants deemed high- risk) maintenance treatment.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Tesaro, Inc.

Lead Sponsor

Trials

57

Recruited

10,600+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5549

Efficacy, safety, and biomarkers of neoadjuvant niraparib ... Thirty pts achieved PR and 12 pts reached SD, resulting in an ORR of 62.5% and a disease control rate (DCR) of 87.5%. BRCAm pts exhibited ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39284381/

final overall survival results from the PRIMA/ENGOT ... - PubMed Niraparib first-line maintenance significantly prolonged progression-free survival (PFS) among patients with newly diagnosed advanced ovarian cancer.

3. zejulahcp.com zejulahcp.com/efficacy/

PRIMA Clinical Study | Efficacy | ZEJULA (niraparib) for HCPs In the control arm, PRIMA patients on placebo received nearly 3-fold higher subsequent PARP inhibitor treatment (48.4%) compared to patients in the ZEJULA arm ( ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1910962

Niraparib in Patients with Newly Diagnosed Advanced ... The PRIMA trial provides data on the benefit of niraparib in patients with advanced ovarian cancer who were receiving neoadjuvant chemotherapy, ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT368336

Efficacy of niraparib maintenance therapy in patients with ... Niraparib significantly extended PFS compared with PBO: the median PFS was 29.4 months for niraparib versus 8.3 months for PBO (HR=0.45; 95% CI, 0.32–0.61; P< ...

6. zejulahcp.com zejulahcp.com/safety/

Safety & Side Effects| ZEJULA (niraparib) for HCPs An established safety and tolerability profile in 1L maintenance therapy of HRD-positive advanced ovarian cancer.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10313963/

Safety and management of niraparib monotherapy in ... Long-term safety data from the NOVA trial confirmed that, with appropriate and early dose modifications, niraparib is well tolerated. Keywords: ...

8. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/zejula

Zejula | European Medicines Agency (EMA) Zejula increased the time women lived without their disease getting worse in two main studies involving over 1,000 women with ovarian cancer, including ...

9. cda-amc.ca cda-amc.ca/sites/default/files/pdf/htis/2024/OS0002-Niraparib-Report.pdf

The Safety of Niraparib in Ovarian Cancer Clinical trials have shown that PARP inhibitors can cause hematological toxicity. A population-based, retrospective cohort study was conducted ...