Phase I Study of Talazoparib in Combination With Radiation Therapy for Locally Recurrent Gynecologic Cancers
Overview
- Phase
- Phase 1
- Intervention
- Quality-of-Life Assessment
- Conditions
- Malignant Female Reproductive System Neoplasm
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 24
- Locations
- 2
- Primary Endpoint
- Maximum tolerated dose (MTD)
- Status
- Recruiting
- Last Updated
- last month
Overview
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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)
Exclusion Criteria
- •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
Arms & Interventions
Treatment (talazoparib, radiation therapy)
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.
Intervention: Quality-of-Life Assessment
Treatment (talazoparib, radiation therapy)
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.
Intervention: Radiation Therapy
Treatment (talazoparib, radiation therapy)
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.
Intervention: Talazoparib
Outcomes
Primary Outcomes
Maximum tolerated dose (MTD)
Time Frame: Up to 30 days
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.
Secondary Outcomes
- 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)
- 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)
- Overall 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)
- 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)