Alpelisib Plus Olaparib in Platinum-resistant/Refractory, High-grade Serous Ovarian Cancer, With no Germline BRCA Mutation Detected

Novartis

Status and phase: Active, not recruiting; Phase 3

Conditions: Ovarian Cancer

Treatments: Drug: Alpelisib; Drug: Pegylated liposomal doxorubicin (PLD); Drug: Olaparib; Drug: Paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT04729387

2019-004682-40 (EudraCT Number)

CBYL719K12301

Details and patient eligibility

About

The objective of this study is to assess the efficacy and safety of the combination of alpelisib and olaparib compared with single agent cytotoxic chemotherapy in patients with platinum resistant or refractory high-grade serous ovarian cancer, with no germline BRCA mutation detected.

Full description

This study will include adult women with platinum resistant or refractory high-grade serous ovarian cancer, with no germline BRCA mutation detected. Participants will be randomized in a 1:1 ratio to either alpelisib plus olaparib or single agent cytotoxic chemotherapy (paclitaxel or PLD) in this open-label, active controlled study.

Participants will continue to receive study treatment until disease progression, unacceptable toxicity that precludes further treatment, or until discontinuation of study treatment due to any other reason. After treatment discontinuation, all participants will enter in the post-treatment follow-up period, which consists of a safety follow-up visit and a 9-week post-progression visit. Once they complete the post-treatment follow-up, participants will then enter the survival follow-up period.

Enrollment: 358 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant has histologically confirmed diagnosis of high-grade serous or high-grade endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
• Measurable disease, i.e., at least one measurable lesion per RECIST 1.1 criteria (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation)
• If no measurable disease is present, the disease should be assessable by Gynecologic Cancer Intergroup criteria (GCIC) for CA-125
• Participant has no germline BRCA1/2 mutation as determined by an FDA approved assay.
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Participant has platinum-resistant (progression within one to six months after completing platinum-based therapy) or platinum refractory disease (progression during treatment or within 4 weeks after the last dose), where platinum-based therapy is not an option, according to the GCIG 5th Ovarian Cancer Consensus Conference definitions. The platinum-based chemotherapy regimen does not necessarily need to be the last regimen the participant received prior to study entry.
• 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.
• Participant has adequate bone marrow and organ function

Exclusion criteria

• Participant has received prior treatment with any PI3K, mTOR or AKT inhibitor.
• Participant is concurrently using other anti-cancer therapy
• Participant is in a state of small or large bowel obstruction or has other impairment of gastrointestinal (GI) function or GI disease
• Participant has had surgery within 14 days prior to starting study drug or has not recovered from major side effects
• Participant has not recovered from all toxicities 5 related to prior anticancer therapies to baseline or NCI CTCAE Version 4.03 Grade ≤1. Exception to this criterion: participants with any grade of alopecia are allowed to enter the study.
• Participants with liver impairment and Child Pugh score B or C
• Participant has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤2 weeks prior to randomization, and who has not recovered to baseline, grade 1 or better from related side effects of such therapy (with the exception of alopecia).
• Participant has a known hypersensitivity to any of the study drugs or excipients

Other inclusion/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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358 participants in 2 patient groups

Alpelisib+olaparib

Experimental group

Description:

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

Treatment:

Drug: Olaparib

Drug: Alpelisib

Paclitaxel or PLD

Active Comparator group

Description:

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:

Drug: Paclitaxel

Drug: Pegylated liposomal doxorubicin (PLD)