This phase II trial studies how effective talazoparib and temozolomide are for treating participants with extensive-stage small cell lung cancer that has come back after an initial chemotherapy treatment. Talazoparib, a PARP inhibitor, may stop the growth of tumor cells by preventing them from repairing their DNA. Chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving talazoparib and temozolomide may work better in treating participants with extensive-stage small cell lung cancer than either one alone.
PRIMARY OBJECTIVES: I. Evaluate the efficacy of talazoparib in combination with temozolomide as measured by objective response rate (ORR). SECONDARY OBJECTIVES: I. To evaluate the efficacy of talazoparib plus temozolomide as measured by progression-free survival (PFS), overall survival, duration of response, and time to response. II. To evaluate the safety, tolerability of talazoparib plus temozolomide. III. To evaluate the pharmacokinetics of talazoparib when given in combination with temozolomide. IV. To evaluate patient reported outcomes per the Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). EXPLORATORY OBJECTIVES: I. To identify potential biomarkers associated with response to study drug treatment. OUTLINE: Participants receive temozolomide orally (PO) on days 1-5 and talazoparib PO once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up at 30 days and then up to 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Given PO
Given PO
CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
Bakersfield, California, United States
St. Joseph Heritage Healthcare
Fullerton, California, United States
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, United States
Orlando Health, Inc. d/b/a Orlando Health UF Health Center
Orlando, Florida, United States
Ft. Wayne Medical Oncology and Hematology, Inc.
Fort Wayne, Indiana, United States
Cancer Center of Kansas
Wichita, Kansas, United States
Objective response rate defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIS)T 1.1
Will be provided along with the corresponding exact 2-sided 95% confidence interval calculated using a method based on the F distribution.
Time frame: Up to 1 year
Progression-Free Survival (PFS) assessed by RECIST 1.1
Will be summarized for the safety analysis (SA) set. Will be summarized using the Kaplan-Meier method and displayed graphically when appropriate.
Time frame: From treatment initiation to time of first documentation of objective tumor progression or death on study due to any cause, whichever occurs first, assessed up to 1 year
PFS assessed by RECIST 1.1
Will be summarized for the SA set. Will be summarized using the Kaplan-Meier method and displayed graphically when appropriate. Median event times and 2-sided 95% confidence interval for each median will be provided.
Time frame: From treatment initiation to time of first documentation of objective tumor progression or death on study due to any cause, whichever occurs first, assessed up to 1 year
Overall survival
Will be summarized using the Kaplan-Meier method and displayed graphically when appropriate.
Time frame: From treatment initiation to death by any cause, assessed up to 1 year
Duration of response (CR or PR) per RECIST 1.1
Will be summarized using the Kaplan-Meier method and displayed graphically when appropriate.
Time frame: From the first documentation of objective tumor response, assessed up to 1 year
Time to response (CR or PR) per RECIST 1.1
Will be summarized using the Kaplan-Meier method and displayed graphically when appropriate.
Time frame: From treatment initiation to the first documentation of objective tumor response, assessed up to 1 year
Pharmacokinetics of talazoparib - steady state trough plasma concentrations
To evaluate the pharmacokinetics (steady state trough plasma concentrations) of talazoparib when given in combination with temozolomide
Time frame: Up to 1 year
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