"OPAL Master Protocol Phase 1B/2 Multicohort Umbrella Study to Evaluate the Safety and Efficacy of Novel Treatments and/or Combinations of Treatments in Participants with Ovarian Cancer (OPAL) OPAL-Supplement C Cohort C: Open-Label Phase 2, Randomized, Controlled Multicenter Study Comparing Niraparib Versus Platinum-Taxane Doublet Chemotherapy as Neoadjuvant Treatment in Participants with Homologous Recombination- Deficient Stage III/IV Ovarian Cancer"

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Tesaro Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Apr 2022 → 1 Apr 2025

Decision date (initial)

2024-02-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

GSK Pharma R&D

External identifiers

EU CT number

2023-505097-16-00

EudraCT number

2021-005392-39

ClinicalTrials.gov

NCT03574779

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy of neoadjuvant niraparib compared with neoadjuvant platinum-taxane doublet chemotherapy after 1 induction cycle of carboplatin-paclitaxel per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in participants with confirmed homologous recombination-deficient (HRd) Stage III to IV ovarian cancer (OC)

Secondary objectives 6

1. To evaluate clinical benefit by Gynecological Cancer Inter Group (GCIG) cancer antigen 125 (CA-125) response criteria
2. To evaluate clinical benefit as measured by progression-free survival (PFS) per RECIST v1.1 by investigator assessment
3. To evaluate participants’ reported overall tolerability toward treatment, overall health status, OC-specific health-related quality of life (HRQoL) and symptoms, and work productivity
4. To evaluate clinical benefit as measured by overall survival (OS)
5. To evaluate clinical benefit as measured by time to first subsequent treatment (TFST)
6. To evaluate the safety and tolerability of neoadjuvant niraparib and neoadjuvant platinum-taxane doublet chemotherapy

Conditions and MedDRA coding

Ovarian Neoplasms

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Participant must be female ≥18 years of age, able to understand the study procedures, and agree to participate in the study by providing written informed consent.
2. Participant must have measurable disease according to RECIST v1.1.
3. Participant has newly diagnosed Stage III or IV ovarian, fallopian tube, or primary peritoneal cancer according to the International Federation of Gynecology and Obstetrics staging criteria.
4. "Participants must provide sufficient tumor tissue at Prescreening and agree to undergo a central HRD tumor testing using a fully validated assay. The participants must be HRd as per central HRD tumor testing result for eligibility. o Participants with a documented germline breast cancer gene (BRCA)1/2 deleterious or suspected deleterious mutations by Sponsor’s permitted test (e.g., BRACAnalysis CDx) may be allowed to enroll prior to receiving the central test results, provided all inclusion criteria are met. However, tumor sample submitted by these participants will still be required for central HRD confirmation. The list of Sponsor’s permitted tests will be provided by the Sponsor. o All participants must agree to provide tumor tissue collected from IDS. o Participant must provide 2 formalin-fixed paraffin-embedded tissue blocks (or slides if blocks are not available) with sufficient tumor content (as confirmed by the Sponsor’s designated central and/or testing laboratory) for central HRD testing at Prescreening and for exploratory biomarker testing at Prescreening or Screening. If sufficient tumor tissue is provided at Prescreening, participants do not need to provide additional tissue at Screening."
5. Participant must have completed 1 run-in cycle of carboplatin-paclitaxel and not experienced disease progression after this treatment. Completion is defined as receiving ≥50% of the prescribed dose of therapy within 5 weeks.
6. Participant must not have known contraindication or uncontrolled hypersensitivity to carboplatin and paclitaxel and their excipients and no known pre-existing conditions that would preclude treatment with these agents.
7. Participant must not have known contraindication or uncontrolled hypersensitivity to niraparib and its excipients.
8. Participant must not have symptomatic ascites or pleural effusions as defined by the following criterion: presence of fluid in the abdominal or pleural cavities requiring removal within 1 week prior to signing the informed consent.
9. Participant must agree to complete patient-reported outcome (PRO) and work productivity questionnaires throughout the study.

Exclusion criteria 8

1. Participant has low-grade or Grade 1 epithelial OC or mucinous, germ cell, transitional cell, carcinosarcoma, or undifferentiated tumor.
2. Participant has contraindications to surgery.
3. Participant has a bowel obstruction by clinical symptoms or computed tomography scan, subocclusive mesenteric disease, abdominal or gastrointestinal fistula, gastrointestinal perforation, or intra-abdominal abscess.
4. Participant has any known history or current diagnosis of myelodysplastic syndrome or acute myeloid leukemia.
5. Participant is at increased bleeding risk due to concurrent conditions (e.g., major injuries or major surgery within the past 28 days prior to the start of study treatment and/or history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).
6. Participant received prior treatment for high-grade non-mucinous epithelial ovarian, fallopian tube, or peritoneal cancer (e.g., prior surgery, immunotherapy, anticancer therapy [with the exception of 1 run-in cycle of carboplatin-paclitaxel], or radiation therapy).
7. Participant is unable to swallow orally administered medication or has a gastrointestinal disorder likely to interfere with absorption of the study medication.
8. Participant received whole blood transfusions in the 2 weeks prior to entry to the study (packed red blood cells and platelet transfusions are acceptable outside of 2 weeks prior to treatment).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint for this cohort is pre-IDS unconfirmed ORR, defined as the percentage of participants with unconfirmed CR or PR on study treatment pre-IDS as assessed per RECIST v1.1 by the Investigator.

Secondary endpoints 9

1. Incidence of CA-125 progression per GCIG CA-125 response criteria
2. PFS, defined as the time from the date of treatment randomization to the date of first documentation of PD per RECIST v1.1 or death by any cause, whichever occurs first, as determined by the Investigator
3. OS, defined as the time from the date of treatment randomization to the date of death by any cause
4. TFST, defined as the time from the date of treatment randomization to the date of first subsequent anticancer therapy or death
5. Safety endpoints include frequency and severity of treatment-emergent adverse events, serious adverse events, AESIs, and dose modification (i.e., interruptions and discontinuations).
6. Change over time in frequency and severity of the items on the Patient Reported Outcomes-Common Terminology Criteria for Adverse Events during neoadjuvant treatment
7. Change from baseline in Functional Assessment of Cancer Therapy-Item GP5 during neoadjuvant treatment
8. Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 items (EORTC Item Library 136) pre-IDS
9. Change from baseline in EORTC Quality of Life Questionnaire for OC gastrointestinal items (EORTC Item Library 137) pre-IDS

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Comparator 2

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Tesaro Inc.

Sponsor organisation

Tesaro Inc.

Address

1000 Winter Street Suite 3300

City

Waltham

Postcode

02451-1230

Country

United States

Scientific contact point

Organisation

Tesaro Inc.

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Tesaro Inc.

Contact name

EU GSK Clinical Trials Call Center

Third parties 10

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications