Alpelisib + Olaparib for Ovarian Cancer

Not currently recruiting at 129 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must not be taking: PI3K, mTOR, AKT inhibitors

Disqualifiers: Bowel obstruction, Liver impairment, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two drugs, alpelisib (Piqray) and olaparib (Lynparza), to determine if they outperform standard chemotherapy for a certain type of ovarian cancer. It targets patients with high-grade serous ovarian cancer who did not benefit from platinum-based treatments and lack the BRCA genetic mutation. Suitable candidates are those with treatment-resistant ovarian cancer who have tried one to three other treatments. As a Phase 3 trial, this study represents the final step before FDA approval, providing patients an opportunity to access potentially groundbreaking treatment.

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 other anti-cancer therapies while participating.

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

Research has shown that the combination of alpelisib and olaparib has been tested before. In these studies, no new or unexpected side effects emerged, suggesting that the combination is generally safe for patients. On average, patients remained on this treatment for about 3.2 months. Most patients took more than 90% of their prescribed doses, indicating good tolerability. These findings offer a clearer idea of what to expect in terms of safety for those considering joining a trial with these medications. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of alpelisib and olaparib for ovarian cancer because it targets the disease in a novel way. Unlike standard treatments like Paclitaxel and Pegylated liposomal Doxorubicin (PLD), which focus on killing cancer cells directly, this combo targets specific pathways that cancer cells use to grow. Alpelisib inhibits a protein involved in cell growth, while olaparib is a PARP inhibitor that prevents cancer cells from repairing themselves. Together, they could offer a more precise attack on ovarian cancer, potentially improving patient outcomes.

What evidence suggests that the combination of alpelisib and olaparib could be an effective treatment for ovarian cancer?

This trial will compare the combination of Alpelisib and Olaparib with standard chemotherapy options for high-grade serous ovarian cancer. Studies have shown that using Alpelisib and Olaparib together does not significantly improve treatment outcomes. On average, cancer worsened after 3.6 months with the combination, compared to 3.9 months with standard chemotherapy. Additionally, the average survival time was 10.0 months with the combination, similar to the 10.6 months with chemotherapy. Overall, the combination did not demonstrate a clear advantage over existing chemotherapy options for this type of cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for patients with high-grade serous ovarian cancer resistant to platinum therapy, without a BRCA mutation. They must have had 1-3 prior treatments and not be candidates for further platinum-based therapy. Participants need measurable disease or assessable CA-125 levels, good organ function, and an ECOG status of 0 or 1.

Inclusion Criteria

I have been diagnosed with a specific type of ovarian, fallopian tube, or peritoneal cancer.

My bone marrow and organs are functioning well.

My cancer can be tracked using a specific blood test for CA-125.

Exclusion Criteria

You are currently using other treatments for cancer.

My liver is not working well (Child Pugh B or C).

I have a blockage or other serious problem in my intestines.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either alpelisib plus olaparib or single agent cytotoxic chemotherapy until disease progression or unacceptable toxicity

Up to 18 months

Post-treatment Follow-up

Participants undergo a safety follow-up visit and a 9-week post-progression visit

9 weeks

Survival Follow-up

Participants are monitored for overall survival

Up to 44 months

What Are the Treatments Tested in This Trial?

Interventions

• Alpelisib
• Olaparib

Trial Overview The study tests the effectiveness and safety of combining alpelisib with olaparib versus standard single-agent chemotherapy in treating high-grade serous ovarian cancer that's unresponsive to platinum treatment.

How Is the Trial Designed?

Group I: Alpelisib+olaparib Experimental Treatment 2 Interventions

Alpelisib 200 mg orally once daily and olaparib 200 mg orally twice daily on a continuous dosing schedule.

Group II: Paclitaxel or PLD Active Control 2 Interventions

Investigator's choice of one of 2 single agent cytotoxic chemotherapies: Paclitaxel 80 mg/m2 intravenously weekly or Pegylated liposomal Doxorubicin (PLD) 40-50 mg/m2 (physician discretion) intravenously every 28 days.

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

Approved in United States as Piqray for:

• Hormone receptor-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen

Approved in European Union as Piqray for:

• Hormone receptor-positive, HER2-negative, PIK3CA-mutated, locally advanced or metastatic breast cancer in combination with fulvestrant

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

Olaparib is a powerful inhibitor of PARP-1 and PARP-2, showing effectiveness in treating ovarian cancer, particularly in patients with germline BRCA mutations.

Phase III trials are currently evaluating olaparib's efficacy as a maintenance therapy after initial treatment in patients with BRCA mutations, highlighting its potential role in long-term cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. Gunderson, CC., Moore, KN.[2016]

The EPIK-O/ENGOT-OV61 trial is a phase III study investigating the combination of the PI3K inhibitor alpelisib and the PARP inhibitor olaparib in patients with platinum-resistant high-grade serous ovarian cancer, aiming to improve outcomes for this difficult-to-treat population.

The primary goal of the trial is to assess progression-free survival, with overall survival as a key secondary endpoint, highlighting the potential of this combination therapy to offer a new treatment option for patients without germline BRCA mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EPIK-O/ENGOT-OV61: alpelisib plus olaparib vs cytotoxic chemotherapy in high-grade serous ovarian cancer (phase III study). Konstantinopoulos, PA., Gonzalez-Martin, A., Cruz, FM., et al.[2022]

Maintenance treatment with olaparib significantly improves progression-free survival (PFS) in patients with newly diagnosed advanced ovarian cancer, reducing the risk of disease progression or death by up to 80% compared to placebo, based on data from the SOLO1 trial involving various patient subgroups.

The benefits of olaparib are consistent across different baseline factors, including surgery type, chemotherapy response, and BRCA mutation status, indicating its broad efficacy as a treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial. DiSilvestro, P., Colombo, N., Scambia, G., et al.[2021]

Olaparib is an effective oral treatment for patients with BRCA mutation-positive ovarian cancer, approved for maintenance therapy after platinum-based chemotherapy, showing good tolerability with common side effects like nausea, fatigue, and anemia being mild to moderate.

Long-term monitoring is recommended due to a low risk of serious hematological complications, such as anemia and myelodysplastic syndrome, ensuring patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. Lheureux, S., Bowering, V., Karakasis, K., et al.[2015]

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.

The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

Olaparib (OLA) monotherapy showed a similar overall objective response rate (ORR) compared to chemotherapy (CT) in patients with relapsed ovarian cancer, with ORR of 24.3% for OLA and 28.3% for CT, indicating comparable efficacy.

In patients with platinum-resistant ovarian cancer (PROC) who had received more than four prior lines of treatment, OLA demonstrated a higher ORR of 22.9% compared to 0% for CT, suggesting that OLA may be more effective in heavily pretreated cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized CLIO/BGOG-ov10 trial of olaparib monotherapy versus physician's choice chemotherapy in relapsed ovarian cancer. Vanderstichele, A., Loverix, L., Busschaert, P., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00225

Primary Analysis of EPIK-O/ENGOT-ov61: Alpelisib Plus ... The median follow-up time was 9.3 months. At data cutoff (April 21, 2023), 33 (18.3%) and 30 (16.9%) patients remained on treatment with ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40700681/

Primary Analysis of EPIK-O/ENGOT-ov61: Alpelisib Plus ... The median follow-up time was 9.3 months. At data cutoff (April 21, 2023), 33 (18.3%) and 30 (16.9%) patients remained on treatment with ...

3. targetedonc.com targetedonc.com/view/combo-of-alpelisib-and-olaparib-falls-short-in-ovarian-cancer

Combo of Alpelisib and Olaparib Falls Short in Ovarian ... Median progression-free survival was 3.6 months with the combination versus 3.9 months with chemotherapy, showing no significant benefit.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9066379/

Phase 1b Clinical Trial with Alpelisib plus Olaparib for Patients ... The median overall survival was 11.8 months (95% CI: 4.2–19.6). Progression-free and overall survival were similar for patients with and without a germline BRCA ...

5. cancernetwork.com cancernetwork.com/view/alpelisib-combo-does-not-extend-pfs-in-high-grade-serous-ovarian-cancer

Alpelisib Combo Does Not Extend PFS in High-Grade ... The median OS was 10.0 months with alpelisib/olaparib vs 10.6 months with chemotherapy (HR, 1.22; 95% CI, 0.87-1.71), and OS events occurred in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04729387

Study Details | NCT04729387 | Alpelisib Plus Olaparib in ... This study will include adult women with platinum resistant or refractory high-grade serous ovarian cancer, with no germline BRCA mutation detected.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204518309057

Olaparib and α-specific PI3K inhibitor alpelisib for patients ... We aimed to assess the safety and identify the recommended phase 2 dose of the PARP inhibitor olaparib in combination with the PI3K inhibitor alpelisib in ...