Phase IB Trial of Radium-223 and Niraparib in Patients With Castrate Resistant Prostate Cancer (NiraRad)

NCT03076203 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 16G.085JT 8649
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 6

Brief Summary

This phase Ib trial studies the side effects and best dose of niraparib when given together with radium Ra223 dichloride in treating subjects with prostate cancer that keeps growing even when the amount of testosterone in the body is reduced to very low levels and has spread from the primary site to the bone. Radium Ra 223 dichloride, acts like calcium to target cancer in the bones and may deliver radiation directly to the bone tumors, limiting damage to the surrounding normal tissue. Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving radium Ra 223 dichloride and niraparib may work better in treating subjects with hormone-resistant prostate cancer metastatic to the bone.

Conditions

Prostate Carcinoma Metastatic to the Bone; Stage IV Prostate Adenocarcinoma; Hormone-refractory Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of niraparib to combine with radium Ra 223 dichloride based on dose limiting toxicities graded by National Cancer Institute, Common Toxicity Criteria, version 4.0

  There will be three dose levels of niraparib combined with standard doses of Radium 223 to be evaluated for safety

  12 weeks

Study Arms (1)

Treatment (niraparib, radium Ra 223 dichloride)

EXPERIMENTAL

Patients receive niraparib orally daily and radium Ra 223 dichloride IV over 1 minute every 4 weeks. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: Niraparib; Radiation: Radium Ra 223 Dichloride

Interventions

Niraparib DRUG

Given orally

Also known as: MK4827, MK-4827

Treatment (niraparib, radium Ra 223 dichloride)

Radium Ra 223 Dichloride RADIATION

Given intravenously

Also known as: BAY 88-8223, Radium 223 Dichloride, RADIUM CHLORIDE RA-223, Xofigo

Treatment (niraparib, radium Ra 223 dichloride)

Eligibility Criteria

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

You may qualify if:

• Histologic or cytologic diagnosis of adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
• Bone metastases
• Documented progressive metastatic CRPC based on at least one of the following criteria:
• PSA progression defined as a miminum of 2 rising PSA levels with a minimum of a 1 week interval and a minimum PSA of 2 ng/mL
• ng/mL is the minimal starting PSA value if confirmed rise is the only indication of progression
• Soft-tissue progression defined as an increase \>= 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions or the appearance of new lesions
• Documented appearance of new lesions by bone scan
• Agree to undergo a tumor/bone marrow biopsy or submit archival tissue. Note: Tissue sample collected from primary or metastatic site is acceptable on study. Once each stratum begins enrollment at the 300mg dose level, 5 subjects from each stratum will complete a bone marrow biopsy. Due to the dose assignment method used in this study, the 10 subjects requiring a bone marrow biopsy on study will be determined on a case by case basis after consent
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Must have received at least 1 line of AR-targeted therapy or androgen bio-synthesis inhibitor (e.g., abiraterone acetate, enzalutamide, apalutamide) for prostate cancer
• Testosterone =\< 50 ng/dL; subjects must continue primary androgen deprivation with an luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist) if they have not undergone orchiectomy
• Subjects on long term (\>= 6 months) first generation anti-androgen therapy (e.g. flutamide, bicalutamide, nilutamide) will need to discontinue anti-androgen therapy for 4 weeks (wash out period) and show evidence of disease progression off the anti-androgen; subjects that have been on a first generation anti-androgen 6 months or less will need to discontinue therapy prior to registration (no wash out period required)
• Subjects on second generation anti-androgen therapy (enzalutamide) or androgen bio-synthesis inhibitor (abiraterone acetate) will need to discontinue therapy 2 weeks prior to registration (wash out period)
• Subjects on treatment with chemotherapy or any investigational therapeutic agent will need to discontinue therapy 4 weeks prior to registration (wash out period)

You may not qualify if:

• Concurrent treatment with any other investigational therapeutic agents
• More than one prior line of chemotherapy
• More than one prior line of therapy with a second generation anti-androgen (enzalutamide, ARN-509, etc.) or androgen bio-synthesis inhibitor (abiraterone acetate, TAK 700, etc.); patient may have had one second generation anti-androgen or androgen bio-synthesis inhibitor but not both sequentially; subjects that have received combination therapy with second generation anti-androgen plus an androgen bio-synthesis inhibitor would be eligible (e.g., enzalutamide plus abiraterone acetate as one line of therapy on a clinical trial). Note, subjects who have had one line of therapy in a hormone-sensitive setting or one line of therapy in castrate resistant setting are eligible for study.
• Prior isotope therapy with strontium-89, samarium or RAD223
• Subjects with known symptomatic brain metastases
• All herbal, alternative and food supplements (i.e. PC-Spes, saw palmetto, St. John's wort, etc.) must be discontinued before registration; Subjects may continue on a daily multi-vitamin, calcium and vitamin D
• Pre-planned concurrent cytotoxic chemotherapy, surgery, or radiation therapy during protocol treatment; radiation therapy is not permitted while on study
• All hormonal-acting agents (including diethylstilbestrol/DES, aldosterone, and spironolactone) must be discontinued before registration; no washout period will be required for any of these agents
• Initiation of bisphosphonate/denosumab therapy during the study; subjects on stable doses of bisphosphonates or the tumor necrosis factor receptor superfamily member 11a, subfamily L (RANK-L) inhibitor, denosumab, which have been started no less than 4 weeks prior to registration, may continue on this medication
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association class III and IV heart failure), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or concurrent medications that alter cardiac conduction
• Subjects with a "currently active" second malignancy other than non-melanoma skin or superficial urothelial cancers are not eligible; Subjects are not considered to have a "currently active" malignancy if they have completed therapy and are now considered without evidence of disease for 2 years
• Subjects with any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
• Subjects with known persistent (\> 4 weeks) \>= grade 2 toxicity from prior cancer therapy
• Subjects with known \>= grade 3 hematological toxicity lasting greater than 7 days with the last chemotherapy regimen
• Subjects with chronic conditions associated with non-malignant abnormal bone growth (e.g., Paget's disease of bone)

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• Janssen, LP: collaborator
• Prostate Cancer Clinical Trials Consortium: collaborator
• Bayer: collaborator

Study Sites (6)

University of Alabama

Birmingham, Alabama, 35249, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Thomas Jefferson University Hospital

MeSH Terms

Interventions

niraparib; radium Ra 223 dichloride

Study Officials

• William Kelly, DO

  Sidney Kimmel Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 21, 2017
• First Posted: March 10, 2017
• Study Start: September 22, 2017
• Primary Completion: January 13, 2020
• Study Completion: November 7, 2022
• Last Updated: April 29, 2025

Record last verified: 2025-04

Locations

US (6)