A study to understand the effect of Niraparib in men with end-stage PCA+
- Conditions
- mCRPC and DNA-repair anomaliesMedDRA version: 20.0Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-002057-38-BE
- Lead Sponsor
- Janssen-Cilag International N.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 300
1. Male
2. >18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place).
3. Signed main study ICF indicating that the subject understands the purpose of, and procedures required for, the study and is willing to participate in the study.
4. Histologically confirmed prostate cancer (mixed histology is acceptable,with the exception of the small cell pure phenotype, which to be excluded).
5.Received at least 1 line of taxane-based chemotherapy for the treatment of mCRPC with documented evidence of disease progression prior to enrollment.
6. Received at least 1 line of AR-targeted therapy (e.g., abiraterone acetate plus prednisone, enzalutamide, apalutamide) for treatment of mCRPC with documented evidence of disease progression prior to enrollment.
7. Biomarker- positive for DNA-repair anomalies.
8. Progression of metastatic prostate cancer in the setting of castrate levels of testosterone =50 ng/dL on a gonadotropin releasing hormone analog (GnRHa), or history of bilateral orchiectomy at study entry defined as having one or more of the following:
a. PSA progression defined by a minimum of 2 rising PSA levels with an interval of =1 week between each determination (per Prostate Cancer Working Group 3 [PCWG3] criteria). The PSA level at the screening visit should be =1 µg/L (1 ng/mL).
b. Radiographic progression of soft tissue by RECIST 1.1 or bone disease by PCWG3 criteria as defined below:
I. Soft tissue disease measurable by RECIST defined as having one or more of the following:
i. Nodal disease (pelvic or extrapelvic [retroperitoneal, mediastinal, thoracic, other]) with lesions =1.5 cm in the short axis.
ii. Visceral disease (lung, liver, adrenal) with lesions =1 in the long axis.
II. Bone disease (non-measurable) defined as having bone lesions in the absence of measurable soft tissue disease
9. Must be able to continue GnRHa during the course of the study if not surgically castrate.
10. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of =2.
11. Must be able to swallow whole capsules.
12. Subject must agree to use medically accepted and highly effective methods of contraception during the course of the study and for 3 months after the last dose of study drug.
13. To avoid risk of drug exposure through the ejaculate (even men with vasectomies), subjects must agree while on study drug and for 3 months following the last dose of study drug to:
a. Use a condom during sexual activity.
b. Not donate sperm.
14. At screening, the following laboratory parameters must be met:
a. Absolute neutrophil count (ANC) =1.5 x 10^9/L
b. Hemoglobin =9.0 g/dL
c. Platelet count =100 x 10^9/L
d. Serum albumin =3 g/dL
e. Creatinine clearance =30 mL/min/1.73 m2
f. Criterion deleted per Amendment 5.
g. Serum total bilirubin =1.5 x upper limit of normal (ULN) or direct bilirubin =1 x ULN (Note: in subjects with Gilbert’s syndrome, if direct bilirubin is =1.5 x ULN, subject may be eligible)
h. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3.0 x ULN
i. CTC count of =1 cells /7.5 mL blood (required only for patients with non-measurable soft tissue disease by RECIST 1.1)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 112
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 188
1. Prior treatment with a PARP inhibitor.
2. Prior platinum-based chemotherapy for the treatment of prostate cancer.
3. Known history or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML).
4. Symptomatic or impending cord compression, except if subject has received definitive treatment for this and demonstrates evidence of clinically stable disease.
5. Symptomatic brain metastases.
6. Known allergies, hypersensitivity, or intolerance to niraparib or its excipients (refer to Investigator's Brochure).
7. Any condition for which, in the opinion of the investigator or sponsor, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
8. Known disorder affecting gastrointestinal absorption.
9. Active cancer (other than prostate cancer; or basal cell or squamous cell skin cancer, non-muscle invasive bladder cancer [stages pTaG1 and pTaG2], or any other cancer in situ currently in complete remission) within 2 years prior to Cycle 1 Day 1.
10. Prior palliative radiotherapy =7 days prior to Cycle 1 Day 1. Radiotherapy given >7 days prior to Cycle 1 Day 1 is permitted as long as any AEs associated with radiotherapy have resolved to Grade 1 or baseline.
11. Criterion deleted per Amendment 5
12. Criterion deleted per Amendment 3.
13. History of clinically significant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, torsades de pointes).
14. HIV positive subjects with 1 or more of the following:
a. Not receiving highly active antiretroviral therapy
b. A change in antiretroviral therapy within 6 months of the start of screening(except if, after consultation with the sponsor on exclusion criterion 14.c, a change is made to avoid a potential drug-drug interaction with the study drug)
c. Receiving antiretroviral therapy that may interfere with the study drug consult the sponsor for review of medication prior to enrollment)
d. CD4 count <350 at screening
e. An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening
15. =30 days prior to Cycle 1 Day 1 had:
a. a transfusion (platelets or red blood cells)
b. chemotherapy
c. hematopoietic growth factors
d. an investigational agent for prostate cancer
e. major surgery
16. Criterion deleted per Amendment 5.
17. Subjects with uncontrolled (persistent) hypertension defined as systolic blood pressure =160 mm Hg or diastolic blood pressure =100 mm Hg despite medical management.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method