Overview

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

Status:
Recruiting
Trial end date:
2021-10-11
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
M.D. Anderson Cancer Center
Collaborator:
National Cancer Institute (NCI)
Treatments:
Talazoparib
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)

- 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

- Note: If cannot fulfill ECOG 0-1, must fulfill inclusion criteria below (minimum
life expectancy of >= 16 weeks)

- 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)

- Patient of child-bearing potential is willing to adhere to using two forms of highly
effective birth control. Condoms with spermicide and one of the following are
acceptable: oral contraceptive or hormonal therapy or placement of an intrauterine
device (IUD). Acceptable non-hormonal birth control methods include: total sexual
abstinence, vasectomized sexual partner plus male condom, tubal occlusion plus male
condom with spermicide, IUD plus male condom+spermicide. Acceptable hormonal methods
include: etonogestrel implants (i.e. Implanon, Norplan), normal and low dose combined
oral pills, norelgestromin/ethinyl estradiol (EE) transdermal system, intravaginal
device (i.e. EE and etonogestrel) or cerazette (desogestrel). All of these would need
to be combined with male condom with spermicide

- Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up

- At least one lesion, not previously irradiated, that can be accurately measured at
baseline as >= 10 mm in the longest diameter (except lymph nodes which must have short
axis >= 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and
which is suitable for accurate repeated measurements

- For inclusion in biomarker endpoint, patients must fulfill the following criterion:

- Provision of informed consent for tumor biopsies * If a patient declines to
participate in tumor biopsies, there will be no penalty or loss of benefit to the
patient. The patient will not be excluded from other aspects of the study
described in this Clinical Study Protocol, so long as they consent to that part

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

- 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

- Patients unable to swallow orally administered medication and patients with
gastrointestinal disorders likely to interfere with absorption of the study medication

- Breast feeding women

- Patients with a known hypersensitivity to talazoparib or any of the excipients of the
product

- Patients with uncontrolled seizures

- Patients requiring pelvic and para-aortic radiotherapy (defined as levels L1/T12)

- Patients with isolated vaginal relapse (i.e. no disease in lymph nodes or else where
in pelvis/abdomen)