A controlled study with Niraparib versus physician's choice in patients with previously-treated, HER2 negative, BRCA mutation-positive breast cancer

• Register: EUCTR
• Last refreshed on: 8 November 2021
• Main ID: EUCTR2013-000684-85-HU
• Date of registration: 16/12/2013
• Prospective Registration: Yes
• Primary sponsor: TESARO Inc.
• Public title: A controlled study with Niraparib versus physician's choice in patients with previously-treated, HER2 negative, BRCA mutation-positive breast cancer
• Scientific title: A phase III, randomized, open label, multicenter, controlled trial of niraparib versus physician’s choice in previously-treated, HER2 negative, germline BRCA mutation-positive breast cancer patients
• Date of first enrolment: 31/01/2014
• Target sample size: 306
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000684-85
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, France, Greece, Hungary, Iceland, Israel, Italy, Netherlands, Poland, Portugal, Spain, United Kingdom, United States

Contacts

• Name: Clinical Trial Mailbox
• Affiliation: TESARO Inc.

• Name: Clinical Trial Mailbox
• Affiliation: TESARO Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histologically or cytologically confirmed HER2-negative metastatic or locally advanced breast cancer that is not amenable to resection or radiation with curative intent.
2. Female and male patients age at least 18 years.
3. Patients with a deleterious or suspected deleterious germline BRCA1 or BRCA2 mutation may be enrolled into the study and randomized based on either local or central laboratory testing of BRCA status (Myriad Genetic Laboratories, Salt Lake City, UT, USA). On- study central confirmation of BRCA status will be performed for those patients who were enrolled based on either a previous Myriad test or a local test. If after inclusion, based on a local test result or a previously done Myriad test, a patient turns out not to have a germline BRCA mutation per central laboratory results (Myriad Genetic Laboratories, Salt Lake City, UT, USA) the patient can still continue on study based on his/her physician discretion and his/her own preference.
4. Measurable disease by RECIST v1.1 or non- measurable disease that is clinically evaluable (except sclerotic-only bone disease; bone-only disease that has a lytic component is allowed).
5. Patients must not have symptomatic uncontrolled brain metastases To be considered controlled, central nervous system (CNS) disease must have undergone treatment (whole brain radiation, radiosurgery or equivalent) at least 1 month previously and the patient has no new or progressive signs or symptoms related to the CNS disease, and are off steroid therapy two weeks.
6. Up to 2 prior cytotoxic regimens for advanced or metastatic breast cancer (not including adjuvant or neo-adjuvant therapy); patients with no prior cytotoxic regimens for advanced or metastatic disease will only be allowed if they relapsed during or within 12 months of (neo-) adjuvant cytotoxic therapy.
7. Prior therapy should have included a taxane and/ or anthracycline (unless contraindication to those) in the neoadjuvant, adjuvant, or advanced/metastatic setting.
a. Hormone receptor positive patients must also have hormone resistant disease; either relapsed while on adjuvant endocrine treatment or within one year of completing adjuvant endocrine treatment, or progression on at least one line of endocrine treatment for advanced cancer.
8. Patients must not have received anticancer chemotherapy, radiotherapy (including palliative radiotherapy), hormonal therapy, biological therapy, or any other investigational therapy within 3 weeks prior to the start of study treatment. Patients with persistent toxicity (except alopecia) > grade 1 from prior cancer therapy will also be excluded. Bisphosphonate and denosumab are allowed.
9. No prior treatment with a known or putative PARP inhibitor (except iniparib). No other anticancer agent (chemotherapy, hormonal therapy, or other agent) is to be permitted during the course of the study for any patient.
10. Patients who have previously received platinum chemotherapy in the metastatic setting are allowed to enroll in the study as long as they did not progress while on or within 8 weeks from the day of the last platinum administration. Patients who received platinum in the (neo-) adjuvant setting are eligible, as long as they relapsed 12 months or more after the last dose of platinum.
11. ECOG performance status 0-2 (Appendix G).
12. Adequate organ function (assessed within 72 hours prior to the first dose):
a. Absolute neutrophil count (ANC) = 1,500 cells/µL
b. Platelets = 100,000 c
Exclusion criteria:
No exclusion criteria are defined per protocol


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

HER2 negative, BRCA germline mutated breast cancer
MedDRA version: 19.1 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Niraparib
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Niraparib
CAS Number: 1038915-60-4
Current Sponsor code: L-001946812-005R, L-001946812 and MK-4827
Other descriptive name: NIRAPARIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Pharmaceutical Form:
INN or Proposed INN: VINORELBINE
CAS Number: 71486-22-1

Trade Name: Gemcitabine-GRY
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: GEMCITABINE
CAS Number: 95058-81-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1000-

Pharmaceutical Form:
INN or Proposed INN: Capecitabine
CAS Number: 154361-50-9
Other descriptive name: CAPECITABINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150 -

Pharmaceutical Form:
INN or Proposed INN: ERIBULIN
CAS Number: 253128-41-5

Pharmaceutical Form:
INN or Proposed INN: Capecitabine
CAS Number: 154361-50-9
Other descriptive name: CAPECITABINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Secondary Objective: To compare overall survival of patients with advanced/metastatic HER2-negative gBRCAmut breast cancer when treated with niraparib as compared to those treated with physician’s choice single agent chemotherapy standards.

- Establish germline BRCA mutation status of screened patients using a centrally provided, validated test. Additional tests will be performed to determine concordance between tests for the purpose of developing a commercial diagnostic test.
- To evaluate safety and tolerability as measured by all AEs
- To compare PFS using investigator assessment of progression
- To evaluate time to treatment failure
- To compare response rate and duration of response
- To compare time to deterioration of health-related quality of life
- To describe subsequent therapies and potential relationships with outcomes
- To assess genetic and non-genetic biomarkers relating to treatment efficacy.

For a detailed listing and for objectives 9 to 10 please refer to the Protocol.

Main Objective: The primary objective of this study is to compare progression-free survival (PFS), as assessed by blinded central review, of patients with advanced/metastatic HER2-negative gBRCAmut breast cancer when treated with niraparib as compared to those treated with physician’s choice single agent chemotherapy standards (eribulin, vinorelbine, gemcitabine or capecitabine).

Primary end point(s): Progression free survival per central review

Timepoint(s) of evaluation of this end point: Per Protocol

Secondary Outcome(s)

Secondary end point(s): 1. Overall survival (key secondary efficacy endpoint).
2. Determine concordance between gBRCAmut tests for the purpose of developing a commercial companion diagnostic test.
3. Safety and tolerability, as documented by AEs and laboratory values
4. PFS using investigator assessment of progression
5. Time to treatment failure
6. Response rate and duration of response
7. Health-related quality of life: QLQ-C30 and EQ5D-5L (see chapter 10).
8. Subsequent therapies and potential relationships with outcomes
9. To assess outcomes by germline mutation BRCA1 vs BRCA2

Timepoint(s) of evaluation of this end point: Per Protocol

Secondary ID(s)

117580

2013-000684-85-IS

PR-30-5010-C

Source(s) of Monetary Support

TESARO Inc.

Ethics review

Status: Approved
Approval date: 14/01/2014
Contact: