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
2 other identifiers
interventional
24
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Sep 2019
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 1, 2019
CompletedFirst Posted
Study publicly available on registry
May 30, 2019
CompletedStudy Start
First participant enrolled
September 26, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2027
March 11, 2026
March 1, 2026
8 years
February 1, 2019
March 10, 2026
Conditions
Outcome Measures
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.
Up to 30 days
Secondary Outcomes (6)
Incidence of adverse events
Up to 2 years
Response rate
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
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
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
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
- +1 more secondary outcomes
Other Outcomes (5)
Level of PAR inhibition
Up to 2 years
Gamma-H2AX and RAD51 foci formation levels
Up to 2 years
Functional Assessment of Cancer Therapy (FACT)
Up to 2 years
- +2 more other outcomes
Study Arms (1)
Treatment (talazoparib, radiation therapy)
EXPERIMENTALPatients 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.
Interventions
Ancillary studies
Undergo radiation therapy
Eligibility Criteria
You may qualify if:
- 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)
- Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (within 28 days prior to administration of study treatment)
- No features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) on peripheral blood smear (within 28 days prior to administration of study treatment)
- White blood cells (WBC) \> 3 x 10\^9/L (within 28 days prior to administration of study treatment)
- Platelet count \>= 100 x 10\^9/L (within 28 days prior to administration of study treatment)
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be =\< 5 x ULN (within 28 days prior to administration of study treatment)
- Serum creatinine =\< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Patients must have a life expectancy \>= 16 weeks
- Evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1. Postmenopausal is defined as:
- Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments, luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50, radiation-induced oophorectomy with last menses \> 1 year ago, chemotherapy-induced menopause with \> 1 year interval since last menses, or surgical sterilization (bilateral oophorectomy or hysterectomy)
- +4 more criteria
You may not qualify if:
- 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
- Participation in another clinical study with an investigational product during the last 4 weeks
- Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for \>= 5 years (will require discussion with study physician)
- Patients receiving any systemic chemotherapy, radiotherapy
- Concomitant use of known CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir
- Concomitant use of known P-gp inhibitors (i.e. dronedarone, quinidine, ranolazine, verapamil, ketoconazole, itraconazole), P-glycoprotein (P-gp) inducers (i.e. rifampin, tipranavir, ritonavir), or breast cancer resistance protein (BCRP) inhibitors (i.e. elacridar \[GF120918\]) should be avoided. If patients are taking any P-gp inhibitors, P-gp inducers, or BRCP inhibitors, they will need to stop them prior to enrolment on the study
- Persistent toxicities (\>= Common Terminology Criteria for Adverse Events \[CTCAE\] grade 2) with the exception of alopecia, caused by previous cancer therapy
- Resting electrocardiogram (ECG) with corrected QT (QTc) \> 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
- Patients with myelodysplastic syndrome/acute myeloid leukemia
- Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 28 days prior to treatment
- Major surgery within 14 days of starting study treatment and patients must have recovered from any effects of any major surgery
- Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, unstable spinal cord compression (untreated and unstable for at least 28 days prior to study entry), superior vena cava syndrome, extensive bilateral lung disease on high resolution computed tomography (CT) scan or any psychiatric disorder that prohibits obtaining informed consent
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (2)
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lilie L Lin
M.D. Anderson Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 1, 2019
First Posted
May 30, 2019
Study Start
September 26, 2019
Primary Completion (Estimated)
October 1, 2027
Study Completion (Estimated)
October 1, 2027
Last Updated
March 11, 2026
Record last verified: 2026-03