This is a phase I, dose escalating study evaluating the safety of combining talazoparib and low dose consolidative thoracic radiotherapy for small cell lung cancer patients. This study will also determine the maximum tolerated dose (MTD) of talazoparib in combination with low dose thoracic radiotherapy. Patients will start on talazoparib on day 1 of study intervention, and will continue to orally take talazoparib until the last day of radiation therapy. Up to 24 patients will be enrolled to the study, where the first 3 patients will start with a starting dose level of talazoparib is 0.5 mg PO once daily. This will increase to 1mg daily with each new cohort.
This is a phase I, dose escalating study evaluating the safety of combination talazoparib and low dose consolidative thoracic radiotherapy for extensive-stage small cell lung cancer patients with at least stable disease after standard of care 4 - 6 cycles of chemotherapy (a platinum agent and etoposide). This study will also determine the maximum tolerated dose (MTD) of talazoparib in combination with low dose thoracic radiotherapy. Secondary objectives will be to examine clinical outcomes, including locoregional recurrence within the radiation field, progression-free survival, overall survival and acute/chronic toxicities up to 1 year. Patients will start on talazoparib on day 1 of study intervention, and will continue to orally take talazoparib until the last day of RT. Patient will start low dose RT on day 6-9, and will continue for 10 fractions throughout 2 weeks. Up to 24 patients will be enrolled to the study, where the first 3 patients will start with a starting dose level of talazoparib is 0.5 mg PO once daily. This will increase to 1mg daily with each new cohort. Patients will be monitored weekly during study treatment, and followed up at 3 weeks, and every 3 months after for 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Dose escalation model to determine the safety and MTD of talazoparib in combination with low dose RT.
Princess Margaret Cancer Center, University Health Network
Toronto, Ontario, Canada
RECRUITINGSafety of Talazoparib in Combination with Low Dose Thoracic Radiotherapy
Safety will be measured by assessing all adverse events as determined by the investigator using CTCAE v.5.0.
Time frame: Up to 3 years upon enrollment
Maximum Tolerated Dose (MTD) of Talazoparib in Combination with Low Dose Thoracic Radiotherapy
MTD will be defined as the maximum dose by a standard 3+3 design
Time frame: Up to 1 year
Loco-regional Recurrence
Loco-regional recurrence will be assessed by using RECIST v1.1 criteria
Time frame: 6 months and 1 year
Progression-Free Survival (PFS)
PFS will be defined as the time of start of radiotherapy to first local/loco-regional or distance recurrence event, or death.
Time frame: 6 months and 1 year
Overall Survival (OS)
OS will be defined as the time from the start of radiotherapy to death from any cause.
Time frame: 6 months and 1 year
Acute Toxicities
Acute toxicities will be assessed by physician-graded CTCAE.
Time frame: Up to 1 year
Chronic Toxicities
Chronic toxicities will be assessed by physician-graded CTCAE.
Time frame: Up to 1 year
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