Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations

NCT03413995 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: J17187IRB00156514
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

The aim of this research is to find out if the study drug rucaparib leads to lowering of PSA levels in men with metastatic prostate cancer that has not yet been treated with androgen deprivation therapy (also referred to as metastatic hormone sensitive prostate cancer) and who have an inherited mutation in a gene involved in repairing DNA damage. The research will also examine if rucaparib is safe in individuals with metastatic prostate cancer. Prior research studies have shown that drugs like rucaparib can be of benefit to patients with advanced metastatic prostate cancer who are resistant to androgen deprivation therapy AND who carry a mutation in a DNA repair gene. We are studying if rucaparib will be an effective treatment for these patients earlier in their treatment course (for example, prior to the start of medicines that lower testosterone level). It is unknown whether rucaparib will have the same benefit in men with metastatic prostate cancer carrying a mutation in a DNA repair gene, prior to the use of medicines that lower your testosterone level.

Conditions

Prostate Cancer Metastatic

Keywords

metastatic hormone sensitive

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Prostate Specific Antigen (PSA) >=50 Response

  Response Rate(PSA) Prostate Specific Antigen to rucaparib for patients with metastatic hormone sensitive prostate cancer harboring germline mutation in homologous recombination DNA (Deoxyribonucleic acid) repair gene. Measured by decline in PSA to 50% of baseline, confirmed with second measurement at least 4 weeks apart.

  4 weeks

Secondary Outcomes (4)

• Number of Participants With Treatment-related Adverse Events

  4 years 8 months

• PSA Progression-free Survival

  2 years

• Progression-free Survival

  2 years

• Objective Response

  2 years

Study Arms (1)

Rucaparib 600 mg BID, continuous dosing

EXPERIMENTAL

Rucaparib 600mg by mouth twice daily, continuous dosing

Drug: Rucaparib

Interventions

Rucaparib DRUG

Continuous dosing

Rucaparib 600 mg BID, continuous dosing

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information.
• Males aged 18 years of age and above
• Histological or cytologic proof of adenocarcinoma of the prostate
• Germline mutation in one or more homologous recombination DNA-repair genes (BRCA1, BRCA2, ATM, CHEK2, NBN, RAD50, RAD51C, RAD51D, PALB2, MRE11, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM) as documented by a clinical CLIA-grade, genetic test (including but not limited to Invitae, Color Genomics, etc)
• All patients must be ineligible for or have declined androgen deprivation therapy (ADT)-based systemic treatment
• Absolute PSA ≥2.0 ng/ml at screening.
• Radiographic evidence of metastatic disease by CT scan and bone scan, performed within the prior 8 weeks.
• Serum testosterone ≥ 100 ng/dl.
• Participants must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
• Hemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT))
• Participants must have creatinine clearance estimated using the Cockcroft-Gault equation of ≥51 mL/min:

You may not qualify if:

• Current active second malignancy (history of non-melanoma skin cancers and superficial bladder cancers are allowed)
• Prior ADT in the past 6 months. Prior ADT in context of neoadjuvant/adjuvant primary is allowed; prior ADT for biochemical recurrence is also allowed, as long as no ADT has been administered in past 6 months and testosterone has recovered (\>100 ng/dl). The total duration of prior ADT should not exceed 24 months.
• Prior oral anti-androgen (e.g. bicalutamide, nilutamide, enzalutamide, apalutamide), or androgen synthesis inhibitor (e.g. abiraterone, orteronel) in the past 6 months is not permitted. 5-alpha reductase inhibitor therapy (e.g. finasteride, dutasteride) is allowed, as long as subject has been stable on medication for past 6 months.
• Presence of visceral (i.e. lung or liver) metastases \>3cm in long-axis dimension.
• Pain due to bone metastases requiring narcotic analgesics.
• Prior treatment with intravenous chemotherapy.
• Use of any prohibited concomitant medications (Appendix B: Medications With the Potential for Drug-Drug Interactions) within the prior 2 weeks.
• Involvement in the planning and/or conduct of the study (applies to both Clovis Oncology staff and/or staff at the study site)
• Previous enrollment in the present study
• Participation in another clinical study with an investigational product during the last 1 month.
• Any previous treatment with a PARP inhibitor, including rucaparib.
• Resting ECG with QTc \> 480 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
• Persistent toxicities (\>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
• Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
• Major surgery within 2 weeks of starting study treatment, and patients must have recovered from any effects of any major surgery.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Clovis Oncology, Inc.: collaborator

Study Sites (2)

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Related Publications (1)

• Nientiedt C, Duensing A, Zschabitz S, Jager D, Hohenfellner M, Stenzinger A, Duensing S. PARP inhibition in prostate cancer. Genes Chromosomes Cancer. 2021 May;60(5):344-351. doi: 10.1002/gcc.22903. Epub 2020 Oct 28.

  PMID: 33084183 DERIVED

MeSH Terms

Interventions

rucaparib

Results Point of Contact

• Title: Mark Markowski, MD
• Organization: Johns Hopkins University

mmarko12@jhmi.edu

410-614-0567

Study Officials

• Mark Markowski, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2018
• First Posted: January 29, 2018
• Study Start: September 10, 2018
• Primary Completion: November 8, 2023
• Study Completion: September 12, 2024
• Last Updated: October 16, 2024
• Results First Posted: October 16, 2024

Record last verified: 2024-09

Locations

US (2)