Enzalutamide and Niraparib in the Treatment of Metastatic Castrate-Resistant Prostate Cancer (CRPC)

NCT02500901 | Terminated Phase 1 Results DMC

• 1 other identifier: HCRN GU14-202
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I study to determine the safety and feasibility of the combination of enzalutamide and niraparib in subjects with metastatic castration-resistant prostate cancer (CRPC).

Conditions

Metastatic Prostate Cancer

Keywords

Enzalutamide; Niraparib; PARP-1 inhibitor; PARP-2 inhibitor; Castrate-Resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) for Subjects Receiving Enzalutamide With Niraparib Without Experiencing Dose-limiting Toxicity(s) (DLT)

  MTD of niraparib in combination with enzalutamide and MTD for phase II testing.

  From the start of combination treatment D29 until 30 days after last dose of study treatment per CTCAE v4, assessed up to 52 weeks

Secondary Outcomes (2)

• Progression-free Survival (PFS) With Enzalutamide and Niraparib Combination Therapy.

  From the date of enrollment until the criteria for disease progression is met as defined by RECIST 1.1 or death from any cause, whichever occurs first, assessed up to 52 weeks

• Objective Response (OR) Rates for All Subjects With Confirmed Partial Response (PR) or Complete Response (CR) Outcomes, Per RECIST v1.1

  From the date of enrollment until the date of documented disease progression or the date of death from any cause, whichever occurs first, assessed up to 52 weeks

Study Arms (1)

Experimental Treatment

EXPERIMENTAL

Subjects will receive enzalutamide 160 mg/day PO in a 28-day lead-in cycle to assess tolerability. If well-tolerated, cycle 1 of combined enzalutamide and niraparib will commence. Enzalutamide will continue at 160 mg PO daily. Niraparib will be administered in three dose-escalation cohorts of 100mg PO, 200mg PO or 300 mg PO daily. Six subjects will be enrolled at each dose level. Each cycle will be 28 days. Combination treatment will continue until documented progression, unmanageable toxicity, or subject or treating investigator decision to discontinue for any reason.

Drug: Enzalutamide; Drug: Niraparib

Interventions

Enzalutamide DRUG

Following completion of 28-day lead-in cycle, enzalutamide 160 mg PO daily will continue to be administered in 28-day cycles until documented progression, unmanageable toxicity, or decision to discontinue for any reason.

Also known as: Xtandi

Experimental Treatment

Niraparib DRUG

Niraparib will be administered daily in three dose-escalation cohorts of 6 subjects per dose levels of 100mg PO, 200mg PO or 300mg PO in 28-day cycles until documented progression, unmanageable toxicity, or decision to discontinue for any reason.

Experimental Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 within 14 days prior to registration.
• Men who are not surgically sterile (vasectomy) must agree to use an acceptable method of contraception. Male subjects with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant during the study must agree to use condoms from the first dose of study drug through at least 120 days after the last dose of study drug. Total abstinence for the same study period is an acceptable alternative.
• Documented histologically or cytologically confirmed adenocarcinoma of the prostate.
• Ongoing androgen deprivation therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or bilateral orchiectomy. Subjects who have not undergone orchiectomy must plan to continue GnRH analogue therapy for the duration of the trial.
• All subjects on oral anti-androgen therapy must have been off therapy for at least 4 weeks prior to registration (6 weeks for bicalutamide) to exclude an anti-androgen withdrawal response. Patients who received secondary anti-androgen therapy and did not exhibit a \>50% PSA decline, or subjects with any rise in PSA, objective or symptomatic progression following anti-androgen withdrawal will not be required to meet this withdrawal requirement.
• Documented metastatic disease with prostate-specific antigen (PSA) progression, radiographic progression, or both, despite receiving luteinizing hormone releasing hormone (LHRH) analogue therapy or orchiectomy with a serum testosterone level of 50 ng/dL or less.
• PSA progression is defined as three successive rising PSA values with an interval of at least one week between determinations.
• Radiographic progression is defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria or at least two new lesions on bone scan.
• At screening the serum testosterone must be 50 ng/dL or less and the PSA must be greater or equal to 2 ng/mL.
• Estimated life expectancy \> 6 months
• Prior treatment of CRPC, including docetaxel, cabazitaxel, sipuleucel-T, or Radium-223 is allowed.
• Prior therapy with abiraterone allowed for a maximum of 9 subjects.
• Prior chemotherapy must be completed at least 28 days prior to registration and the participant subject must have recovered from the acute toxic effects.

You may not qualify if:

• Prior enzalutamide or other next-generation androgen receptor- (AR) targeting therapy.
• Prior PARP-inhibitor therapy.
• History of or active central nervous system (CNS) metastases. Subjects with neurological symptoms must undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to exclude brain metastasis.
• Radioisotope or external beam radiation exposure in the last 4 weeks. Exposure to strontium, regardless of when exposure occurred.
• Prior radiation to 25% or more of the bone marrow.
• Treatment with any investigational agent within 28 days prior to registration.
• Known significant immunodeficiency as determined by the site investigator.
• Prior malignancy except for adequately treated basal cell or squamous cell skin cancer, or other cancer for which the subject has been disease-free or stable for at least one year.
• Prolonged QTc over 470 ms.
• History of seizure.
• Clinically significant active infections on systemic therapy as judged by the site investigator.

Sponsors & Collaborators

• Paul Mathew, MD: lead
• Hoosier Cancer Research Network: collaborator
• Tesaro, Inc.: collaborator

Study Sites (1)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Related Links

• Hoosier Cancer Research Network Website

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; niraparib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Limitations and Caveats

Study was terminated early by the funder.

Results Point of Contact

• Title: Clinicaltrials.gov Results Coordinator
• Organization: Hoosier Cancer Research Network

jsmith@hoosiercancer.org

317-643-5842

Study Officials

• Paul Mathew, M.D.

  Hoosier Cancer Research Network

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: July 2, 2015
• First Posted: July 17, 2015
• Study Start: March 1, 2016
• Primary Completion: May 10, 2016
• Study Completion: May 10, 2016
• Last Updated: October 21, 2019
• Results First Posted: October 21, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)