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

ConditionsMalignant Female Reproductive System NeoplasmRecurrent Cervical CarcinomaRecurrent Endometrial CarcinomaRecurrent Fallopian Tube CarcinomaRecurrent Ovarian CarcinomaRecurrent Primary Peritoneal CarcinomaRecurrent Vaginal CarcinomaStage IV Cervical Cancer AJCC v8Stage IV Fallopian Tube Cancer AJCC v8Stage IV Ovarian Cancer AJCC v8Stage IV Primary Peritoneal Cancer AJCC v8Stage IV Uterine Corpus Cancer AJCC v8Stage IV Vaginal Cancer AJCC v8Stage IVA Cervical Cancer AJCC v8Stage IVA Fallopian Tube Cancer AJCC v8Stage IVA Ovarian Cancer AJCC v8Stage IVA Primary Peritoneal Cancer AJCC v8Stage IVA Uterine Corpus Cancer AJCC v8Stage IVA Vaginal Cancer AJCC v8Stage IVB Cervical Cancer AJCC v8Stage IVB Fallopian Tube Cancer AJCC v8Stage IVB Ovarian Cancer AJCC v8Stage IVB Primary Peritoneal Cancer AJCC v8Stage IVB Uterine Corpus Cancer AJCC v8Stage IVB Vaginal Cancer AJCC v8
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorM.D. Anderson Cancer Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Provision of informed consent prior to any study specific procedures

Histologically-confirmed recurrent ovarian, fallopian tube, primary peritoneal cancer, endometrial, vaginal, or cervical cancer in the abdomen and pelvis

Subjects with stage IV disease are eligible as long as disease elsewhere (other than the site(s) to receive radiation therapy [RT]) is undetectable or stable (>= 3 months) and immediate chemotherapy is not required. Willingness to discontinue any cytotoxic chemotherapeutic agents, immunotherapy, biologic therapy, and targeted therapies at least three weeks prior to start of investigational therapy

Hemoglobin >= 10.0 g/dL and no blood transfusions in the 28 days prior to entry/randomization (choose whichever is most applicable to the study) (within 28 days prior to administration of study treatment)

Disqualifiers

Ascites, peritoneal carcinomatosis, hepatic metastases

Prior radiotherapy in the region of planned radiotherapy

Chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the 3 weeks prior to start of therapy

Previous enrollment in the present study

Trial design

Design model

Single group

Treatments tested in this trial

  • Quality-of-Life Assessment

    Other intervention

    Ancillary studies

  • Radiation Therapy

    Radiation

    Undergo radiation therapy

  • Talazoparib

    Drug

    Given PO

Treatment groups

24 Participants
are divided into 1 treatment group
Group A: Treatment (talazoparib, radiation therapy)Experimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Maximum 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

Secondary outcomes

1

Incidence of adverse events

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

Time frame
Up to 2 years
2

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
3

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
4

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

Other outcomes

1

Level of PAR inhibition

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.

Time frame
Up to 2 years
2

Gamma-H2AX and RAD51 foci formation levels

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.

Time frame
Up to 2 years
3

Functional Assessment of Cancer Therapy (FACT)

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.

Time frame
Up to 2 years
4

Expanded Prostate Cancer Index Composite (EPIC)

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.

Time frame
Up to 2 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

M.D. Anderson Cancer Center

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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