This phase I trial studies the side effects and best dose of talazoparib in combination with radiation therapy and to see how well they work in treating patients with gynecologic cancers that have come back after previous treatment (recurrent). Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving talazoparib in combination with radiation therapy may work better in treating patients with gynecologic cancers.
PRIMARY OBJECTIVE: I. To determine the safety, tolerability, and maximally tolerated dose (MTD) of talazoparib combining talazoparib and fractionated radiotherapy in patients with refractory or recurrent ovarian, fallopian tube, primary peritoneal, cervical, or vaginal or endometrial carcinoma. SECONDARY OBJECTIVES: I. To determine the safety profile of talazoparib in combination with fractionated radiotherapy for recurrent gynecologic cancers. II. To determine a preliminary anti-cancer activity of this combination at the MTD. EXPLORATORY OBJECTIVES: I. To explore the potential feasibility of using biomarkers in tumor tissue, whole blood or serum as predictive markers of treatment response. II. To explore the impact of talazoparib when combined with radiotherapy for recurrent gynecologic cancers on 1) patient reported acute gastrointestinal (GI) toxicity and 2) overall longitudinal quality of life at week 5 of therapy. OUTLINE: This is a dose escalation study of talazoparib. Patients receive talazoparib orally (PO) once daily (QD) beginning on days -10 to -7 and continuing for up to 8 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy 5 days a week (Monday-Friday) for up to 7 weeks. After completion of study treatment, patients are followed up at 1, 3, 6, 9, and 12 months, and then every 6 months for up to 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
RECRUITINGM D Anderson Cancer Center
Houston, Texas, United States
RECRUITINGMaximum tolerated dose (MTD)
MTD is determined by dose limiting toxicity (DLT). The MTD will be determine using the time-to-event Bayesian optimal interval (TITE-BOIN) model, and it is defined as the dose for which the isotonic estimate of the DLT rate is closest to the target DLT rate.
Time frame: Up to 30 days
Incidence of adverse events
Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE).
Time frame: Up to 2 years
Response rate
Anti-cancer activity will be measured by response rate by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Each endpoint will be analyzed using the cumulative incidence method when competing events exist or the product-limit method of Kaplan and Meier when competing events are absent. Additionally, competing risk regression or proportional hazards modeling, whichever is appropriate, will be used to examine each endpoint while adjusting for disease. Estimates and 95% intervals will be reported.
Time frame: From the start of study treatment until documentation of local or regional recurrence, progression, time to next therapy, and death, assessed up to 2 years
Local control rate
Will be analyzed using the cumulative incidence method when competing events exist or the product-limit method of Kaplan and Meier when competing events are absent. Additionally, competing risk regression or proportional hazards modeling, whichever is appropriate, will be used to examine each endpoint while adjusting for disease. Local control will be summarized as freedom from local failure calculated as 1 minus the cumulative incidence of local or regional recurrence. Estimates and 95% intervals will be reported.
Time frame: From the start of study treatment until documentation of local or regional recurrence, progression, time to next therapy, and death, assessed up to 2 years
Time to progression
Will be analyzed using the cumulative incidence method when competing events exist or the product-limit method of Kaplan and Meier when competing events are absent. Additionally, competing risk regression or proportional hazards modeling, whichever is appropriate, will be used to examine each endpoint while adjusting for disease. Estimates and 95% intervals will be reported.
Time frame: From the start of study treatment until documentation of local or regional recurrence, progression, time to next therapy, and death, assessed up to 2 years
Progression-free survival
Will be analyzed using the cumulative incidence method when competing events exist or the product-limit method of Kaplan and Meier when competing events are absent. Additionally, competing risk regression or proportional hazards modeling, whichever is appropriate, will be used to examine each endpoint while adjusting for disease. Estimates and 95% intervals will be reported.
Time frame: From the start of study treatment until documentation of local or regional recurrence, progression, time to next therapy, and death, assessed up to 2 years
Overall survival
Will be analyzed using the cumulative incidence method when competing events exist or the product-limit method of Kaplan and Meier when competing events are absent. Additionally, competing risk regression or proportional hazards modeling, whichever is appropriate, will be used to examine each endpoint while adjusting for disease. Estimates and 95% intervals will be reported.
Time frame: From the start of study treatment until documentation of local or regional recurrence, progression, time to next therapy, and death, assessed up to 2 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.