Clinical Trials /

Rucaparib in Nonmetastatic prOstAte With BRCAness

NCT03533946

Description:

This is a single arm, open label, phase II trial to assess efficacy of rucaparib.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Rucaparib in Nonmetastatic prOstAte With BRCAness
  • Official Title: A Phase II Study of Rucaparib Monotherapy in Nonmetastatic, Hormone-Sensitive Prostate Cancer Demonstrating "BRCAness" Genotype (ROAR)

Clinical Trial IDs

  • ORG STUDY ID: HCI111833
  • NCT ID: NCT03533946

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
RucaparibRubracaRucaparib, all patients

Purpose

This is a single arm, open label, phase II trial to assess efficacy of rucaparib.

Trial Arms

NameTypeDescriptionInterventions
Rucaparib, all patientsExperimentalSingle Arm study, all patients will get rucaparib
  • Rucaparib

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically proven adenocarcinoma of the prostate with BRCAness (defined as a
             deleterious alteration in one or more of the following genes: ATM, ATM, ATR, BARD1,
             BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, ERCC3, FAM175A, FANCA, FANCL, GEN1, HDAC2,
             MLH1, MRE11, NBN, PALB2, PPP2R2A, RAD51, RAD54L) from soft-tissue based genomic
             testing or liquid biopsy based genomic testing.

          -  Rising PSA based on PCWG3 criteria without radiographic evidence of metastatic disease
             as assessed by CT scans and technetium nuclear medicine bone scan. Subject must
             demonstrate a PSA doubling time of ≤ 10 months.

          -  ECOG/Zubrod score of 0-2.

          -  Subject must not have received any prior systemic therapy for prostate cancer except
             for adjuvant hormone treatment in the context of localized prostate cancer. Patients
             may have not received ADT treatment longer than 24 months.

          -  Be 18 years old at the time the informed consent form is signed.

          -  Demonstrate adequate organ function as defined in the table in the protocol, all
             screening labs should be performed within 28 days of treatment initiation.

          -  Highly effective barrier methods must be used with all sexual activity and
             contraception methods must be practiced for all subjects throughout the study and for
             at least 6 months after last rucaparib treatment administration if the risk of
             conception exists (section 7.2).

          -  Recovery to baseline or Grade ≤ 1 CTCAE v5.0 from toxicities related to any prior
             treatments (surgery, radiotherapy or other antineoplastic therapy), unless AE(s) are
             clinically nonsignificant and/or stable on supportive therapy.

          -  Last dose of any antineoplastic therapy ≥ 2 weeks (including neoadjuvant chemotherapy,
             radiation therapy, small molecule inhibitors, radiation, and/or other investigational
             anticancer agents).

          -  Subject is participating in the Total Cancer Care study (IRB # 89989).

          -  Subject is able to provide informed consent and willing to sign an approved consent
             form that conforms to federal and institutional guidelines.

        Exclusion Criteria:

          -  ADT therapy either by surgical castration or with GnRH agonist or antagonist or on
             androgen synthesis blocker or androgen receptor antagonists previously for the
             treatment of biochemically recurrent prostate cancer.

          -  Prior localized prostate cancer treatment with chemotherapy, radiation, antibody
             therapy or other immunotherapy, gene therapy, vaccine therapy, or angiogenesis
             inhibitors.

          -  Arterial or venous thrombi (including cerebrovascular accident), myocardial
             infarction, admission for unstable angina, cardiac angioplasty, or stenting within the
             last 3 months prior to screening.

          -  Pre-existing duodenal stent, recent or existing bowel obstruction, and/or any
             gastrointestinal disorder or defect that would, in the opinion of the Investigator,
             interfere with absorption of rucaparib.

          -  Inability to swallow tablets.

          -  Evidence or history of bleeding disorder.

          -  Participation in another investigational drug trial within 14 days prior to Day 1 (or
             5 times the half-life of the drug, whichever is longer) or exposure to more than three
             new investigational agents within 12 months prior to Day 1.

          -  Acute illness (eg, nausea, vomiting, fever, diarrhea) within 14 days prior to Day 1,
             unless mild in severity and approved by the Principal Investigator.

          -  Active second malignancy, with the exception of curatively treated non-melanoma skin
             cancer, carcinoma in situ, or superficial bladder cancer with curative intent.

          -  Prior treatment with any PARP inhibitor, mitoxantrone, cyclophosphamide, or any
             platinum based chemotherapy.

          -  Clinically significant (i.e., active) cardiovascular disease: cerebral vascular
             accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months
             prior to enrollment), unstable angina, congestive heart failure (> New York Heart
             Association Classification Class II), or serious cardiac arrhythmia requiring
             medication.

          -  Other severe acute or chronic medical conditions including cardiovascular, endocrine,
             neurologic, pulmonary or psychiatric conditions including recent (within the past
             year) or active suicidal ideation or behavior; or laboratory abnormalities that may
             increase the risk associated with study participation or study treatment
             administration or may interfere with the interpretation of study results and, in the
             judgment of the investigator, would make the patient inappropriate for entry into this
             study.

          -  Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks
             before first dose of study treatment. Complete wound healing from major surgery must
             have occurred 1 month before first dose and from minor surgery (eg, simple excision,
             tooth extraction) at least 28 days before first dose. Subjects with clinically
             relevant ongoing complications from prior surgery are not eligible.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:50% Reduction in PSA levels
Time Frame:Monthly while on treatment; Most patients are expected to be on treatment for approximately 18 months
Safety Issue:
Description:To assess the proportion of patients with a 50% reduction in PSA levels (PSA50) compared to the baseline value at the time of study enrollment. Endpoint: the levels of PSA will be monitored monthly for comparison to baseline levels.

Secondary Outcome Measures

Measure:Adverse Events that Occur
Time Frame:Every visit while on treatment and 1 year of follow-up - Most patients are expected to be on treatment for approximately 18 months, and then one additional year
Safety Issue:
Description:To assess the safety of rucaparib in patients with biochemically recurrent hormone-sensitive prostate cancer. Endpoint: adverse events will be monitored regularly during patient enrollment and follow up to assess the toxicity of rucaparib using validated CTCAE v5.0 criteria.
Measure:PSA Progression Free Survival
Time Frame:Monthly while on treatment; Most patients are expected to be on treatment for approximately 18 months
Safety Issue:
Description:The levels of PSA will be monitored monthly for comparison to baseline levels until the time of PSA progression, as defined by Prostate Cancer Working Group 3 (PCWG3) criteria
Measure:Proportion of patients with an undetectable PSA after initiation at therapy
Time Frame:At 6 and 12 months
Safety Issue:
Description:To assess the proportion of patients with an undetectable PSA after initiation of PARP therapy at 6 and 12 months. Endpoint: the levels of PSA will be monitored monthly for comparison to baseline levels to determine when PSA becomes undetectable.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Utah

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