What side effects are associated with this type of intervention?

Common treatments for ovarian cancer, such as PI3K inhibitors (e.g., Alpelisib) and PARP inhibitors (e.g., Olaparib), have distinct side effect profiles. PI3K inhibitors often cause hyperglycemia, rash, diarrhea, and fatigue. PARP inhibitors are associated with nausea, fatigue, anemia, and neutropenia. Both classes of drugs can lead to gastrointestinal disturbances and hematologic toxicities, which require careful monitoring and management.

What prior FDA approvals exist?

The FDA has approved several PARP inhibitors for the treatment of ovarian cancer, particularly for patients with BRCA mutations or those with platinum-sensitive disease. Notable PARP inhibitors include Olaparib, Rucaparib, and Niraparib. Olaparib was one of the first PARP inhibitors approved and has shown efficacy in maintenance therapy for platinum-sensitive relapsed ovarian cancer. Rucaparib and Niraparib have also been approved for similar indications. While PI3K inhibitors like Alpelisib are being studied, they are not yet standard treatments for ovarian cancer. The combination of these inhibitors aims to target specific pathways involved in cancer cell survival and proliferation.

What other types of research exist?

Promising novel alternatives for ovarian cancer treatment in 2024 include: 1) Pembrolizumab plus Lenvatinib, which has shown significant improvements in progression-free survival and overall survival in patients with proficient MMR tumors. 2) Bevacizumab combined with platinum-based chemotherapy followed by Bevacizumab maintenance, which has been effective in platinum-sensitive recurrent epithelial ovarian cancer. 3) Other angiogenesis inhibitors like Cediranib, which are in various stages of development and have shown potential in clinical trials.

← Back to Search

PI3K Inhibitor

Alpelisib + Olaparib for Ovarian Cancer

Phase 3

Waitlist Available

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participant has histologically confirmed diagnosis of high-grade serous or high-grade endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer

Participant must have received at least one but no more than three prior systemic treatment regimens and for whom single-agent chemotherapy is appropriate as the next line of treatment

Must not have

Participants with liver impairment and Child Pugh score B or C

Participant is in a state of small or large bowel obstruction or has other impairment of gastrointestinal (GI) function or GI disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from baseline up to approximately 44 months

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include nausea, fatigue, blood count changes, increased sugar levels (due to alpelisib), anemia, digestive issues from olaparib; plus common chemo-related side effects like hair loss and nerve damage.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

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

Select...

I've had 1-3 treatments before and now need chemotherapy alone.

Select...

I do not have a BRCA1 or BRCA2 gene mutation.

Select...

I am fully active or can carry out light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

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

Select...

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

Select...

I have been treated with drugs targeting PI3K, mTOR, or AKT.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from baseline up to approximately 44 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from baseline up to approximately 44 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and from baseline up to approximately 44 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression Free Survival (PFS) based on Blinded Independent Review Committee (BIRC) assessment using RECIST 1.1 criteria

Secondary study objectives

Area under the curve calculated to the end of a dosing interval (tau) at steady-state (AUCtau) of alpelisib and olaparib

Area under the curve from time zero to the last measurable concentration sampling time (AUClast)of alpelisib and olaparib

Change from baseline in Function Assessment of Cancer Therapy-Ovarian Trial Outcome Index (FACT-O TOI)

+10 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Alpelisib+olaparibExperimental Treatment2 Interventions

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

Group II: Paclitaxel or PLDActive Control2 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Alpelisib

2018

Completed Phase 3

~960

Olaparib

2007

Completed Phase 4

~2190

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for ovarian cancer, such as PI3K inhibitors and PARP inhibitors, work by targeting specific pathways crucial for cancer cell survival and proliferation. PI3K inhibitors like alpelisib disrupt the PI3K/AKT/mTOR pathway, reducing tumor growth and promoting cancer cell death. PARP inhibitors like olaparib prevent the repair of DNA damage in cancer cells, leading to cell death, particularly in those with BRCA mutations. These targeted therapies are important for ovarian cancer patients as they can offer more effective and potentially less toxic treatment options compared to traditional chemotherapy, especially for those with specific genetic profiles.

Clinical Benefits of Olaparib in Mexican Ovarian Cancer Patients With Founder Mutation BRCA1-Del ex9-12.