Advanced or recurrent solid tumors for which there is no accepted standard treatment or for which standard treatment has failed. Patients may also be eligible if they are unable or decline to undergo standard therapy because it has limited antitumor efficacy or has significant toxicidty. MedDRA version: 19.0 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864
Conditions
Interventions
Product Name: Talazoparib
Product Code: BMN 673
Pharmaceutical Form: Capsule
INN or Proposed INN: N/A
CAS Number: 1373431-65-2
Sponsors
Medivation, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically or cytologically documented, unresectable, locally advanced or metastatic solid tumor for which no standard therapy is recognized or for which standard therapy has failed. Patients may also be eligible if they are unable or decline to undergo standard therapy because it has limited antitumor efficacy or has significant toxicity. • 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 prostate-specific antigen (PSA; prostate cancer), and/or CA 19-9 (pancreatic cancer). • Eastern Cooperative Oncology Group (ECOG) performance status = 1. • Have adequate organ function as defined below: o Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 X upper limit of normal (ULN); if liver function abnormalities are due to hepatic metastasis, then AST and ALT may be = 5 X ULN; o Total serum bilirubin = 1.5 X ULN; o Hemoglobin = 9.0 g/dL with last transfusion at least 28 days before Cycle 1, Day 1; o Absolute neutrophil count (ANC) = 1500/mm3; o Platelet count = 100,000/mm3; • Able to take oral medications. • Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures. • Sexually active patients must be willing to use an acceptable method of contraception such as double barrier contraception during treatment and for 30 days after the last dose of BMN 673. • Females of childbearing potential must have a negative serum pregnancy test at screening and be willing to have additional serum pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to screening, or who have had total hysterectomy. • Willing and able to comply with all study procedures Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: • Has not recovered (recovery is defined as National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events [CTCAE v4.03] grade = 1) from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting the inclusion requirements stated in the inclusion criterion. • Part 2 Expansion: Prior treatment with a PARP inhibitor. • Has history of central nervous system (CNS) metastasis. • Any antitumor systemic cytotoxic therapies within 28 days before Cycle 1, Day 1 (6 weeks for nitrosoureas or mitomycin-C), treatment with immune modulators (including, but not limited to, corticosteroids, cyclosporine and tacrolimus; locally active treatments such as Beconase are allowed) within 28 days before Cycle 1, Day 1, or radiotherapy within 28 days before Cycle 1, Day 1. • Prior high-dose chemotherapy with bone marrow or stem cell transplant • Is known to have human immunodeficiency virus (HIV) or has active hepatitis C virus (HCV), or active hepatitis B virus (HBV). • Has had major surgery within 28 days before Cycle 1, Day 1. • Has active peptic ulcer disease. • Active gastrointestinal tract disease with malabsorption syndrome. • Requirement for IV alimentation. • Prior surgical procedures affecting absorption. • Uncontrolled inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis). • Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication • Breastfeeding at screening or planning to become pregnant (self or partner) at any time during study participation. • Use of any investigational product or investigational medical device within 28 days before Cycle 1, Day 1. • Concurrent disease or condition that would interfere with study participation or safety, such as: o Active, clinically significant infection requiring the use of parenteral antimicrobial agents, or grade > 2 by NCI CTCAE (v4.03) within 14 days before Cycle 1, Day 1; o Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders; o Non-healing wound, ulcer, or bone fracture. o Bone marrow disorder including myelodysplasia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to establish the maximum tolerated dose (MTD) of daily, oral BMN 673; Secondary Objective: The secondary objectives of the study are to: • assess the safety and tolerability of BMN 673 • determine the PK profile of BMN 673 • determine the Recommended Phase 2 Dose (RP2D) of BMN 673 • assess preliminary efficacy of BMN 673 • assess change in pharmacodynamic activity in blood, surrogate and/or fresh tumor tissue before and during treatment ; Primary end point(s): Safety: The following safety outcome(s) measurements(s) will be assessed: • incidence of adverse events (AEs) and dose limiting toxicities (DLTs) • change in clinical laboratory tests (serum chemistry and hematology) • change in electrocardiogram (ECG) results • change in vital signs • change in physical examination • change in concomitant medication use Additional safety assessments may be made at any time if clinically indicated. Efficacy: A preliminary assessment of efficacy is a secondary objective of this study. The following efficacy measurements will be assessed: • objective response rate (ORR), as determined by the RECIST (v1.1) in patients with measurable solid tumors (Eisenhauer, 2009, Eur.J.Cancer); or as determined by measurement prostate-specific antigen (PSA; in patients with prostate cancer) or CA-125 (for patients with ovarian cancer) and/or CA 19-9 (for patients with pancreatic cancer) assessed with standard guidelines (Rustin, 2004, J Natl.Cancer Inst.), (Scher, 2008, J Clin Oncol), (Melnik, 2010, Mol.Cancer Ther.). Postbaseline tumor assessments will be performed using the same method as at baseline. Samples for tumor markers | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Number of participants with adverse events •Determine the pharmacokinetic (PK) profile of BMN 673 •Determine the Recommended Phase 2 Dose (RP2D) of oral daily BMN 673 •Assess preliminary efficacy of BMN 673 by Response Rate, based on RECIST (Response Evaluation Criteria In Solid Tumors) ; Timepoint(s) of evaluation of this end point: •Assessed after each visit until completion of the study (Estimated duration is 24-30 months) •Assessed at each visit in cycle 1 - 5 (Estimated duration is 24 months) •Assessed after each visit until completion of the study (Estimated duration is 24-30 months) •Assessed approximately every 8 weeks (Estimated duration is 24-30 months) | — |
Countries
United Kingdom
Contacts
Public ContactMedical Officer
Medivation, Inc.
Outcome results
None listed