A Phase 2, Multicenter, Open-Label, Exploratory Biomarker Study of Talazoparib (BMN 673) Monotherapy in Patients with Recurrent or Metastatic Solid Tumors
- Conditions
- Recurrent or Metastatic Solid TumorsMedDRA version: 18.0Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-004011-37-ES
- Lead Sponsor
- BioMarin Pharmaceutical Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 100
- 18 years of age or older
- Histologically confirmed breast cancer or epithelial ovarian cancer (including fallopian tube or primary peritoneal cancer)
- Recurrent or metastatic disease for which talazoparib deemed an acceptable therapy by the investigator
- No more than 4 prior chemotherapy regimens for metastatic disease (no limit on prior hormonal therapies)
- Disease amenable to biopsy and willing to undergo mandatory biopsy at Screening and again at disease progression.
- Have sufficient archival formalin-fixed paraffin-embedded (FFPE) resected primary ovarian tumor tissue or sufficient archival core breast tumor tissue (1 slide with 5-µm-thick sections and 9 slides with 10-µm-thick sections, minimum 20% tumor cellularity). [Note: Fresh core breast tumor tissue may be used if archival tissue is not available.]
- Fresh tumor biopsy collected at Screening must be of sufficient quantity with minimum 25 mm2 surface area and 40 ?m thickness (eg, 2 mm x 15 mm core) and minimum two cores.
- Measurable disease per RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status ?1
- Adequate organ function as defined below:
o Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ?2.5x upper limit of normal (ULN) [Note: ?5xULN if liver function abnormalities are due to hepatic metastasis]
o Total serum bilirubin ?1.5xULN [Note: ?3xULN for Gilbert's Syndrome]
o Calculated creatinine clearance ?30 mL/min
o Hemoglobin ?9.0 g/dL with last transfusion ?14 days before first study drug
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 study-related procedures
- If sexually active, willing to use acceptable method of contraception (eg, double-barrier) during treatment and for 30 days after last dose of study drug
- If females with childbearing potential, a negative serum pregnancy test at screening and willing to have additional serum and urine pregnancy tests during the study. [Note: Females without childbearing potential include those in menopause ?2 years, with tubal ligation ?1 year before screening, or with 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 100
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
? Has deleterious or pathogenic germline BRCA1 or BRCA2 mutation
? If received prior platinum therapy, disease progression or recurrence within 6 months after last dose of platinum
? HER2-positive breast cancer or inflammatory breast cancer
? Has not recovered from acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting the inclusion criteria
? Prior treatment with a PARP inhibitor
? History of central nervous system (CNS) metastasis (except adequately treated brain metastasis that is stable and does not require corticosteroids for management of CNS symptoms)
? Cytotoxic chemotherapy or anti-hormone therapy ?21 days before first day of study drug (?42 days if mitomycin C was the last chemotherapy) or radiotherapy ?21 days before first day of study drug
? Major surgery ?21 days before first day of study drug
? Any investigational product or investigational medical device ?28 days before first day of study drug
? Prior malignancy except for any of the following:
o Carcinoma in situ of the cervix or non-melanoma skin cancer
o A cancer diagnosed and definitively treated ?5 years previously with no evidence of recurrence
? Known to be human immunodeficiency virus (HIV) positive
? Known active replicating hepatitis C or B virus
? Myocardial infarction ?6 months before first day of study drug, symptomatic congestive heart failure (New York Heart Association > Class II), unstable angina, or unstable cardiac arrhythmia requiring medication
? Breast-feeding at screening or planning to become pregnant (self or partner) any time during study participation
? Concurrent disease or prior surgical procedure affecting talazoparib absorption
? Concurrent disease or condition that would interfere with study participation or safety, such as the following:
o Active, clinically significant infection either Grade > 2 (NCI CTCAE v4.03) or requiring parenteral antimicrobial agents ?14 days before first day of study drug
o Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders
o Non-healing wound, ulcer, or bone fracture
o Bone marrow disorders, including myelodysplasia
? Known hypersensitivity to any talazoparib component
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to determine a potential association between HRD score and objective tumor response to talazoparib (BMN 673) treatment.;Secondary Objective: Secondary objectives include safety, PK, and preliminary talazoparib (BMN 673) efficacy.;Primary end point(s): Objective response rate (ORR) according to revised Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in patients with breast cancer and ovarian cancer.;Timepoint(s) of evaluation of this end point: Anticipated in about 24-30 months following first patient enrolled
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Progression-free survival (PFS), Duration of response (DOR) for objective responders, and Gynecologic Cancer InterGroup (GCIG) CA125 response in patients with ovarian cancer;Timepoint(s) of evaluation of this end point: Anticipated in about 24-30 months following first patient enrolled