Alpelisib + Olaparib for Ovarian Cancer

Recruiting at 113 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

358 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether a combination of two drugs, alpelisib and olaparib, is more effective than standard chemotherapy for women with a specific type of ovarian cancer that doesn't respond well to usual treatments. Alpelisib works by stopping cancer cells from growing, while olaparib makes it harder for them to repair themselves. Olaparib has shown effectiveness in treating ovarian cancer, particularly in patients with certain genetic backgrounds.

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.

What data supports the effectiveness of the drug combination Alpelisib and Olaparib for ovarian cancer?

Research shows that Olaparib, one of the drugs in the combination, significantly improves progression-free survival in patients with advanced ovarian cancer who have a BRCA mutation. Additionally, early trials suggest that combining Alpelisib with Olaparib may be effective for certain types of ovarian cancer that are resistant to other treatments. ^{1 2 3 4 5}

Is the combination of Alpelisib and Olaparib safe for humans?

The combination of Alpelisib and Olaparib has been studied for safety in a phase 1b trial for high-grade serous ovarian cancer, showing it to be generally tolerable. Additionally, preclinical data and a phase Ib trial indicated the combination's tolerability in platinum-resistant, non-BRCA-mutated ovarian cancer. ^{1 4 5 6 7}

How is the drug combination of Alpelisib and Olaparib unique for treating ovarian cancer?

The combination of Alpelisib and Olaparib is unique because it targets platinum-resistant ovarian cancer without BRCA mutations, using Alpelisib to inhibit a specific enzyme (PI3K) and Olaparib to block DNA repair, offering a novel approach compared to standard chemotherapy. ^{1 3 4 5 7}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Randomized CLIO/BGOG-ov10 trial of olaparib monotherapy versus physician's choice chemotherapy in relapsed ovarian cancer. [2022]

2. United States 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. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. [2015]

4. England pubmed.ncbi.nlm.nih.gov

EPIK-O/ENGOT-OV61: alpelisib plus olaparib vs cytotoxic chemotherapy in high-grade serous ovarian cancer (phase III study). [2022]

5. England 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Phase 1b Clinical Trial with Alpelisib plus Olaparib for Patients with Advanced Triple-Negative Breast Cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

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