Study Stopped
Other- Protocol moved to Disapproved
Talazoparib in Treating Patients With Advanced or Metastatic Solid Tumors That Cannot Be Removed by Surgery and Liver or Kidney Dysfunction
A Phase I Study of Single Agent Talazoparib (BMN 673) in Advanced Cancer Patients With Hepatic and Renal Dysfunction
4 other identifiers
interventional
N/A
0 countries
N/A
Brief Summary
This phase I trial studies the side effects and best dose of talazoparib in treating patients with solid tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or have spread to other places in the body (metastatic) and cannot be removed by surgery and liver or kidney dysfunction. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Trial Health
Trial Health Score
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 2, 2015
CompletedFirst Posted
Study publicly available on registry
October 5, 2015
CompletedStudy Start
First participant enrolled
June 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2018
CompletedApril 24, 2017
April 1, 2017
2.3 years
October 2, 2015
April 20, 2017
Conditions
Outcome Measures
Primary Outcomes (3)
Incidence of toxicity, graded according to the National Cancer Institute (NCI) CTCAE version 4.03
Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest. Adverse events will be summarized using all adverse events experienced, although a sub-analysis may be conducted including only those adverse events in which the treating physician deems possibly, probably or definitely attributable to study treatment.
Up to 4 weeks after completion of study treatment
Recommended phase 2 dose of talazoparib, graded according to NCI CTCAE version 4.0
Up to 28 days
Tolerability of talazoparib in patients with varying degrees of hepatic and renal dysfunction
Up to 4 weeks after completion of study treatment
Secondary Outcomes (5)
Biomarkers associated with response or resistance to talazoparib
Up to 4 weeks after completion of study treatment
Objective response, graded according to RECIST version 1.1
Up to 4 weeks after completion of study treatment
PK profiles of talazoparib in patients with varying degrees of hepatic and renal dysfunction
Pre-dose, and 30 minutes, 1, 2, 4, 6, 8, and 24 hours post-dose on day 1 of course 2, and pre-dose on day 1 of courses 3 and 4
Progression-free survival (PFS)
Up to 4 weeks after completion of study treatment
Response rate
Up to 4 weeks after completion of study treatment
Other Outcomes (1)
The pharmacodynamic effects of talazoparib
Up to day 2 of course 2
Study Arms (1)
Treatment (talazoparib)
EXPERIMENTALPatients receive talazoparib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions
Eligibility Criteria
You may qualify if:
- Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
- Any advanced solid malignancy will be eligible, with a strong preference for tumors that are known to commonly harbor defects in homologous recombination repair including triple-negative breast cancer, high-grade serous ovarian cancer, non-small cell lung cancer, small cell lung cancer, mesothelioma castration-resistant prostate cancer, pancreatic adenocarcinoma, gastric cancer and head \& neck squamous cell cancer
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria
- All patients must have completed any prior chemotherapy, targeted therapy, radiotherapy (unless palliative doses which must be discussed with study principal investigator), and surgery, \>= 28 days before study entry
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Life expectancy of greater than 3 months
- Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
- Leukocytes \>= 3,000/mcL
- Absolute neutrophil count \>= 1,500/mcL
- Platelets \>= 100,000/mcL
- Hemoglobin \>= 90 g/L
- Hepatic and renal function meeting the strata as outlined below; nota bene (NB): patients must fulfill both total bilirubin and serum glutamic-oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) criteria and creatinine function to be included in a group; however, if a patient's total bilirubin and SGOT/AST and creatinine levels indicate different groups, the patient may be enrolled in the indicated group with the greatest degree of liver dysfunction; all liver and renal function tests must be completed within 24 hours prior to the start of treatment; Note: patients on dialysis will not be eligible
- Group A: hepatic function: normal function (bilirubin =\< upper limit of normal \[ULN\]; AST =\< ULN); renal function: normal function (creatinine clearance \[CrCl\] \>= 60 mL/min)
- Group B: hepatic function: normal function (bilirubin =\< ULN; AST =\< ULN); renal function: moderate dysfunction (CrCl \>= 30 and \< 60 ml/min)
- Group C: hepatic function: normal function (bilirubin =\< ULN; AST =\< ULN); renal function: severe dysfunction (CrCl \>= 15 and \< 30 ml/min)
- +7 more criteria
You may not qualify if:
- Prior treatment with talazoparib or a poly(adenosine diphosphate \[ADP\]-ribosyl)ation (PARP)1/2 inhibitor; prior treatment with other agents that inhibit deoxyribonucleic acid (DNA) repair (i.e. WEE1 homolog \[S. pombe\] \[WEE1\] inhibitors, ataxia telangiectasia mutated \[ATM\] inhibitors), is allowed; if there are any questions, please contact the study's principal investigator
- Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy must not be given within 28 days prior to study enrollment; for daily or weekly chemotherapy without the potential for delayed toxicity, a washout period of 14 days prior to enrollment may be acceptable, and questions related to this can be discussed with study principal investigator
- Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders
- Known hypersensitivity to any of the components of talazoparib
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to talazoparib
- Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of talazoparib and during the study
- Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression; patients with treated central nervous system (CNS) metastasis, no longer requiring steroid therapy are potentially eligible; patients with primary glioblastoma multiforme not requiring steroid therapy will be eligible
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements
- Any other known malignancy within 3 years (with the exception of non-melanoma skin cancer that had undergone curative treatment, cervical cancer in situ, or ductal/lobular carcinoma in situ of the breast that has underwent local treatment); consult the Cancer Therapy Evaluation Program (CTEP) medical monitor if unsure whether second malignancies meet the requirements specified above
- Women of childbearing potential should be advised to avoid pregnancy and use effective methods of contraception for 4 months after study treatment is completed; men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception for at least 4 months after study treatment is completed; if a female patient or a female partner of a patient becomes pregnant while the patient receives talazoparib, the potential hazard to the fetus should be explained to the patient and partner (as applicable)
- Active hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (patients with chronic or cleared HBV and HCV infection are eligible)
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
- Any condition or medical problem in addition to the underlying malignancy and organ dysfunction that the investigator feels would pose unacceptable risk
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Daniel Renouf
University Health Network Princess Margaret Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 2, 2015
First Posted
October 5, 2015
Study Start
June 1, 2016
Primary Completion
October 1, 2018
Last Updated
April 24, 2017
Record last verified: 2017-04