Study of Talazoparib, a PARP Inhibitor, in Patients With Advanced or Recurrent Solid Tumors
Condition: Advanced or Recurrent Solid Tumors; Breast Neoplasms; Ovarian Cancer, Epithelial; Ewing Sarcoma; Small Cell Lung Carcinoma; Prostate Cancer; Pancreas Cancer
MeSH terms: Breast Neoplasms; Sarcoma, Ewing; Pancreatic Neoplasms; Small Cell Lung Carcinoma; Carcinoma, Ovarian Epithelial; Recurrence
Intervention: Talazoparib
Intervention description: Oral capsule with multiple dosage forms given once daily
Intervention MeSH terms: Talazoparib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Masking: None (Open Label)
Enrollment: 113.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: BRCA1 Protein; BRCA2 Protein

Summary:

      This is a single-arm, open-label study to assess the safety, pharmacokinetics,
      pharmacodynamics, and preliminary efficacy of talazoparib in patients with advanced tumors
      with DNA-repair pathway deficiencies. There will be 2 parts to the study: a dose escalation
      phase in which the maximum tolerated dose will be defined, and a dose expansion phase.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically documented, unresectable, locally advanced or
             metastatic solid tumor

          -  Must have available archived tumor tissue (formalin-fixed paraffin-embedded) [FFPE].

          -  18 years of age or older.

          -  Have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST, v1.1)
             or increased CA-125 (ovarian cancer) or PSA (prostate cancer) and/or CA 19-9
             (pancreatic cancer).

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

          -  Have adequate organ function

          -  Able to take oral medications.

          -  Willing and able to provide informed consent.

          -  Sexually active patients must be willing to use an acceptable method of contraception.

          -  Females of childbearing potential must have a negative serum pregnancy test at
             screening.

          -  Willing and able to comply with all study procedures.

        Part 2 Dose Expansion Tumor Types:

          -  Breast and ovarian cancer patients with deleterious or pathogenic BRCA mutations who
             have received no more than 4 prior regimens for metastatic disease.

          -  Prostate or pancreatic cancer patients with deleterious or pathogenic BRCA mutations
             who have received no more than 2 prior regimens for metastatic disease.

          -  Small cell lung cancer (SCLC) patients who have received no more than one prior
             regimen for SCLC.

          -  Ewing's sarcoma patients who have received no more than 3 prior regimens for
             metastatic disease.

        Exclusion Criteria:

          -  Part 2 Expansion: Prior treatment with a PARP inhibitor.

          -  Has history of central nervous system (CNS) metastasis.

             * Exception: In patients with SCLC, history of adequately treated brain metastasis who
             do not require corticosteroids for management of CNS symptoms.

          -  Has had major surgery within 28 days before Cycle 1, Day 1.

          -  Has active peptic ulcer disease.

          -  Active gastrointestinal tract disease with malabsorption syndrome.

          -  Pregnant or breastfeeding at screening or planning to become pregnant (in each case,
             either oneself or one's partner) at any time during the study.