Phase II Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (TRIUMPH)


Condition: Prostate Cancer Metastatic

Intervention:

  • Drug: Rucaparib

Purpose: 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.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03413995

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Primary Outcome Measures:

  • Measure: Response Rate(PSA)to rucaparib for pts with met. hormone sensitive prostate ca harboring germline mutation in homologous recombination DNA repair gene. Measured by decline in PSA to 50% of baseline, confirmed w/second measurement at least 4 weeks apart.
  • Time Frame: 4 weeks
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
  • Time Frame: 2 years
  • Safety Issue:
  • Measure: PSA progression-free survival, defined as a time from initiation of rucaparib therapy until PSA increase of 25 %, confirmed with another measurement at least 3 weeks later
  • Time Frame: 6 months
  • Safety Issue:
  • Measure: Progression-free survival, defined as time from initiation of rucaparib therapy to radiographic or clinical progression or death, whichever comes first.
  • Time Frame: 2 years
  • Safety Issue:
  • Measure: Objective response rate, defined as the proportion of patients achieving a complete or partial response in target lesions found on radiographic scans
  • Time Frame: 2 years
  • Safety Issue:

Estimated Enrollment: 30

Study Start Date: September 10, 2018

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  • 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:
  • Estimated creatinine clearance = (140-age [years]) x weight (kg) serum creatinine (mg/dL) x 72
  • ECOG Performance Status <2
  • Participants must have a life expectancy ≥ 12 months.
  • Male participants and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination [see appendix E for acceptable methods], throughout the period of taking study treatment and for 6 months after last dose of study drug to prevent pregnancy in a partner.

Exclusion Criteria:

  • 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.
  • Poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 6 months) myocardial infarction, uncontrolled major seizure disorder, extensive interstitial bilateral lung disease, or any psychiatric disorder that prohibits obtaining informed consent.
  • Unable to swallow orally administered medication or gastrointestinal disorders likely to interfere with absorption of the study medication.
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for HIV. Known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
  • Known hypersensitivity to rucaparib or any of the excipients of the product.
  • Whole blood transfusions in the last 30 days prior to entry to the study.

Contact:

  • Mark Markowski, MD
  • 410-614-0567

Location:

  • Johns Hopkins Hospital
  • Baltimore Maryland 21205 United States

View trial on ClinicalTrials.gov