Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Gland and Hormone Related Diseases

Digestive System Diseases

Rare Diseases

Uterine Cervical Neoplasms

Recurrence

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Vaginal Neoplasms

Genital Neoplasms, Female

Fallopian Tube Neoplasms

Peritoneal Neoplasms

Endometrial Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Uterine Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Fallopian Tube Diseases

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Vaginal Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Vaginal Cancer

Fallopian Tube Cancer

Antineoplastic Agents

All Drugs and Chemicals

Talazoparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Patients receive talazoparib PO 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.

Quality-of-Life Assessment

Radiation Therapy

Lilie Lin

Lilie L. Lin

Lilie L Lin

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.

Talazoparib and Radiation Therapy in Treating Patients With Locally Recurrent Gynecologic Cancers

Phase I Study of Talazoparib in Combination With Radiation Therapy for Locally Recurrent Gynecologic Cancers

Ninety-five percent confidence intervals will be generated for all summary statistics. No formal statistical testing will be completed. Summary statistics and box plots will be created to examine Functional Assessment of Cancer Therapy (FACT) component scores at each assessment time as well as to examine the Expanded Prostate Cancer Index Composite (EPIC) bowel questionnaire measured at week 5. Models will be created to examine impact of dosage upon quality of life (QoL) and acute gastrointestinal (GI) toxicity. In the case of QoL, the models will examine QoL over time using linear mixed models, and we will test for an interaction effect between dose and time to examine whether any potential effects of dose upon QoL change over time. No testing will be completed; 95% confidence intervals will be created for all model coefficients.

Gamma-H2AX and RAD51 foci formation levels in peripheral mononuclear cells and CTCs will be tested for association with PAR inhibition using Pearson and Spearman correlation methods. An association between germline and tumor BRCA mutation status and PAR inhibition, H2AX. Ninety-five percent confidence intervals will be generated for all summary statistics. No formal statistical testing will be completed.

Will examine the component scores at each assessment time. as well as to examine the Expanded Prostate Cancer Index Composite (EPIC) bowel questionnaire measured at week 5. . No testing will be completed; 95% confidence intervals will be created for all model coefficients.

Will examine the Expanded Prostate Cancer Index Composite (EPIC) bowel questionnaire measured at week 5. No testing will be completed; 95% confidence intervals will be created for all model coefficients.

Models will be created to examine impact of dosage upon quality of life (QoL). In the case of QoL, the models will examine QoL over time using linear mixed models, and we will test for an interaction effect between dose and time to examine whether any potential effects of dose upon QoL change over time. No testing will be completed; 95% confidence intervals will be created for all model coefficients.

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.

Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE).

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.

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.

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.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for stage ivb vaginal cancer ajcc v8