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: 9 March 2015
• Main ID: EUCTR2013-000684-85-IT
• Date of registration: 19/02/2014
• 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: 16/06/2014
• Target sample size: 306
• Recruitment status: Authorised-recruitment may be ongoing or finished
• 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

Countries of recruitment

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

Contacts

• Name: Robert Martell
• Affiliation: TESARO Inc.

• Name: Robert Martell
• 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. Germline BRCA1 or BRCA2 mutation that is considered deleterious or suspected deleterious (include those mutations or translocations termed “deleterious” or “suspected deleterious” according to Myriad reporting) by analysis at a reference laboratory (Myriad Genetic Laboratories, Salt Lake City, UT, USA, or Myriad GmbH, Martinsried, Germany).
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 that included a taxane and anthracycline, if not contraindicated.
7. Prior therapy should have included an anthracycline and a taxane (unless contraindication to those) in the neoadjuvant, adjuvant, or advanced/metastatic setting.
a. Hormone receptor positive patients must also have hormone resistant disease (progression during at least one prior hormonal therapy) for which chemotherapy is indicated.
8. Patients must not have received anticancer chemotherapy, 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 is 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 must not be platinum resistant defined as: progression of cancer during or within 6 months of completion of prior platinum treatment.
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 cells/µL
c. Hemoglobin = 9 g/dL
d. Serum creatinine = 1.5 × upper limit of normal (ULN) or = 60 mL/min using Cockcroft-Gault equation
e. Total bilirubin = 1.5 × ULN OR direct bilirubin = ULN
f. Aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 × ULN or < 5 × ULN with liver metastases
13. Patients able to swallow and retain oral tablets
14. Female patients must not be pregnant or breast feeding
a. Female patient of childbearing potential must have a negative serum pregnancy test.
15. Patients of child bearing potential and their partners with whom they are sexually active must agree to the use of 2 highly effective forms of contraception from randomization, throughout the study and until 3 months after the l
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: 16.1 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: Capsule, soft
INN or Proposed INN: VINORELBINE
CAS Number: 71486-22-1
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 80-

Pharmaceutical Form:
INN or Proposed INN: GEMCITABINE
CAS Number: 95058-81-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0-

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

Product Name: Halaven
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ERIBULIN
CAS Number: 253128-41-5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.44-

Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: VINORELBINE
CAS Number: 71486-22-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

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

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

Secondary Objective: (1) Key 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.
(2) Other Secondary Objectives:
- 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 (HRQoL
- To describe subsequent therapies and potential relationships with outcomes
- To assess genetic and non-genetic biomarkers relating to treatment efficacy.
- To assess outcomes by germline mutation BRCA1 vs BRCA2

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).

Secondary Outcome(s)

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

Secondary end point(s): 1. Overall survival.
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

Secondary ID(s)

117580

2013-000684-85-IS

PR-30-5010-C

Source(s) of Monetary Support

TESARO Inc.