Patient case: 50-year-old male with prostate cancer; genetic feature: ATM deletion

Clinical trial: Rucaparib in Nonmetastatic prOstAte With BRCAness

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


Eligibility: Inclusion Criteria:
  -  Histologically proven adenocarcinoma of the prostate with BRCAness (defined as an alteration in one or more of the following genes: 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.
  -  Subjects must have received definitive local therapy, which includes prostatectomy or radiation therapy with curative intent. Neoadjuvant or adjuvant treatments can have been given within this time.
  -  Subject must not have received any prior systemic therapy for localized prostate cancer unless used in the context of definitive local therapy. Patients may receive salvage hormone therapy with radiotherapy, as long as salvage hormone therapy does not exceed 6 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 within the context of their definitive local therapy for their prostate cancer, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
  -  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 salvage therapy for prostate cancer treatment with chemotherapy, 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 at the time of enrollment: 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.

Relevance to patient case: not relevant