A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Niraparib Maintenance Treatment in Patients with Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy

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

14 Sep 2016 → 30 Sep 2025

Decision date (initial)

2024-05-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

TESARO, Inc., a GSK Company

External identifiers

EU CT number

2023-508010-42-00

EudraCT number

2015-000952-11

ClinicalTrials.gov

NCT02655016

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacodynamic, Efficacy, Pharmacokinetic, Therapy, Safety

The primary objective of this study is to evaluate the efficacy of niraparib versus placebo as maintenance treatment, as measured by progression-free survival (PFS), in patients with Stage III or IV ovarian cancer (including fallopian and peritoneal cancers) with a complete response (CR) or partial response (PR) following front-line platinum-based chemotherapy treatment.

Secondary objectives 2

1. 1. To evaluate additional measures of clinical benefit for niraparib versus placebo as maintenance treatment, such as overall survival (OS), patient-reported outcomes (PROs), time to first subsequent therapy (TFST), and time to progression on the next anticancer therapy (PFS2).
2. 2. To evaluate the safety and tolerability of niraparib versus placebo.

Conditions and MedDRA coding

Homologous recombination deficiency advanced ovarian cancer

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Patients 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. Patients must have adequate organ function, defined as follows (Note: complete blood count [CBC] test should be obtained without transfusion or receipt of stimulating factors within 2 weeks before obtaining screening blood sample): a. Absolute neutrophil count ≥1,500/µL b. Platelets ≥100,000/µL c. Hemoglobin ≥10 g/dL d. Serum creatinine ≤1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation. e. Total bilirubin ≤1.5 x ULN f. Aspartate aminotransferase and alanine aminotransferase ≤2.5 x ULN unless liver metastases are present, in which case they must be ≤5 x ULN.
3. All patients must agree to complete PROs during study and then at 4 weeks, 8 weeks, 12 weeks, and 24 weeks after EOT, regardless of subsequent treatment.
4. Patients must have formalin-fixed, paraffin-embedded tumor samples available from the primary cancer or agree to undergo fresh biopsy prior to study treatment initiation.
5. Histological and staging criteria: a. Patients must have histologically diagnosed high-grade serous or endometrioid, or high-grade predominantly serous or endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that is Stage III or IV according to FIGO criteria.
6. Surgical criteria: a. Patients with inoperable Stage III and IV disease are eligible; b. All Stage IV patients with operable disease are eligible; c. Patients with stage III or IV disease treated with neoadjuvant chemotherapy and interval debulking surgery are eligible; d. Patients with stage III disease who have visible residual disease after primary debulking surgery are eligible.
7. Chemotherapy criteria: a. Patients who have received intraperitoneal chemotherapy are eligible; b. All patients must have had ≥6 and ≤9 cycles of platinum-based therapy; Patients must have had ≥2 post-operative cycles of platinum-based therapy following interval debulking surgery; d. Patients must have physician assessed CR or PR after ≥3 cycles of therapy; e. Patients must have either CA-125 in the normal range or CA-125 decrease by more than 90% during their front-line therapy that is stable for at least 7 days (i.e., no increase >15% from nadir).
8. Patients must be randomized within 12 weeks of the first day of the last cycle of chemotherapy.
9. All patients must agree to undergo central tumor HRD testing. a. The central HRD test result must be available for randomization as it is a stratification factor. Patients with documented gBRCA1 or gBRCA2 mutation or sBRCA1/2 mutation may be randomized without HRD test results. b. The tumor sample may be submitted for HRD testing prior to the screening period if it appears the patient is likely to meet other eligibility requirements. Patients are not required to have repeat HRD testing if HRD result is “not determined” (e.g., due to insufficient tumor specimen). c. Patients with known HRD test results from a commercially available source are allowed to participate in the study; however, they must still agree to submit a tumor sample for central HRD testing. The results of the central HRD testing must be available prior to randomization and must be used for stratification. Additional testing related to HRD may be performed on the sample used for screening and randomization post randomization. If there is inadequate tissue remaining subsequent to the screening analysis, sites may be requested to provide additional tissue from the block used for screening purposes.
10. Patients of childbearing potential must have a negative serum or urine pregnancy test (beta human chorionic gonadotropin [hCG]) within 7 days prior to receiving the first dose of study treatment.
11. Patients must be postmenopausal, free from menses for >1 year, surgically sterilized, or willing to use adequate contraception to prevent pregnancy or must agree to abstain from activities that could result in pregnancy throughout the study, starting with enrollment through 180 days after the last dose of study treatment.
12. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
13. Patients must be able to take oral medications.

Exclusion criteria 22

1. Patient has mucinous or clear cell subtypes of epithelial ovarian cancer, carcinosarcoma or undifferentiated ovarian cancer
2. Patients with Stage III disease who have had complete cytoreduction (i.e., no visible residual disease) after primary debulking surgery
3. Patient has undergone more than two debulking surgeries
4. Patient is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment and for up to 180 days after the last dose of study treatment
5. Patient has a known hypersensitivity to the components of niraparib or its excipients;
6. Patient is simultaneously enrolled in any clinical trial of niraparib or any other investigational therapy
7. Patient has received prior treatment with a known PARP inhibitor or has participated in a study where any treatment arm included administration of a known PARP inhibitor
8. Patient is planning to donate blood during the study or for 90 days after the last dose of study treatment.
9. Patient has been diagnosed and/or treated for invasive cancer less than 5 years prior to study enrollment. Note: Patients with definitively treated uterine cervical or urinary tract carcinoma in situ, non-melanomatous skin cancer or ductal carcinoma in situ (DCIS) of the breast are not excluded.
10. Patient has known brain or leptomeningeal metastases that are untreated or uncontrolled (i.e., new or worsening symptom or signs, or unstable steroid requirements)
11. Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection
12. Patient is to receive bevacizumab as maintenance treatment. Patients who have received bevacizumab with their first-line platinum-based therapy but are unable to receive bevacizumab as maintenance therapy due to adverse events or for any other reason are not excluded from study as long as the last dose of bevacizumab was received ≥28 days prior to signing the main informed consent form
13. Patient is immunocompromised (patients with splenectomy are allowed).
14. Patient has known, active hepatic disease (i.e., hepatitis B or C).
15. Patient has had investigational therapy administered within 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study
16. Patient has undergone major surgery (per Investigator judgment) within 3 weeks of starting the study or patient has not recovered from any effects of any major surgery
17. Patient has had drainage of ascites within 4 weeks prior to enrollment
18. Patient has undergone palliative radiotherapy encompassing >20% of the bone marrow within 1 week of the first dose of study treatment
19. Patient has a condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results or interfere with the patient’s participation for the full duration of the study treatment, including: a. Patient received a transfusion (platelets or red blood cells) within 2 weeks of the first dose of study treatment; b. Patient received colony-stimulating factors (e.g., granulocyte colony stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 2 weeks prior to the first dose of study treatment.
20. Patient has had any known ≥Grade 3 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted >4 weeks
21. Patient has any known history or current diagnosis of MDS or AML
22. Patient has a corrected QT interval (QTc) prolongation >480 milliseconds at screening

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is PFS, defined as the time from treatment randomization to the earlier date of assessment of progression or death by any cause in the absence of progression.

Secondary endpoints 1

1. The secondary endpoints include the following: • OS • Observed changes from baseline in the following PROs: − FOSI − EQ-5D-5L − EORTC-QLQ-C30 − EORTC-QLQ-OV28 • Time to first subsequent therapy (TFST) • PFS2

Investigational products

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

Test 1

Placebo 1

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 14

Locations

12 EU/EEA countries · 49 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

Documents 125 files

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

Application history

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