Overview

Talazoparib in Treating Patients With Advanced or Metastatic Solid Tumors That Cannot Be Removed by Surgery and Liver or Kidney Dysfunction

Status:
Withdrawn
Trial end date:
1969-12-31
Target enrollment:
0
Participant gender:
All
Summary
This phase I trial studies the side effects and best dose of talazoparib in treating patients with solid tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or have spread to other places in the body (metastatic) and cannot be removed by surgery and liver or kidney dysfunction. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National Cancer Institute (NCI)
Treatments:
Talazoparib
Criteria
Inclusion Criteria:

- Patients must have histologically confirmed malignancy that is metastatic or
unresectable and for which standard curative or palliative measures do not exist or
are no longer effective

- Any advanced solid malignancy will be eligible, with a strong preference for tumors
that are known to commonly harbor defects in homologous recombination repair including
triple-negative breast cancer, high-grade serous ovarian cancer, non-small cell lung
cancer, small cell lung cancer, mesothelioma castration-resistant prostate cancer,
pancreatic adenocarcinoma, gastric cancer and head & neck squamous cell cancer

- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
version (v)1.1 criteria

- All patients must have completed any prior chemotherapy, targeted therapy,
radiotherapy (unless palliative doses which must be discussed with study principal
investigator), and surgery, >= 28 days before study entry

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

- Life expectancy of greater than 3 months

- Able to swallow and retain orally-administered medication and does not have any
clinically significant gastrointestinal abnormalities that may alter absorption such
as malabsorption syndrome or major resection of the stomach or bowels

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Hemoglobin >= 90 g/L

- Hepatic and renal function meeting the strata as outlined below; nota bene (NB):
patients must fulfill both total bilirubin and serum glutamic-oxaloacetic transaminase
(SGOT)/aspartate aminotransferase (AST) criteria and creatinine function to be
included in a group; however, if a patient's total bilirubin and SGOT/AST and
creatinine levels indicate different groups, the patient may be enrolled in the
indicated group with the greatest degree of liver dysfunction; all liver and renal
function tests must be completed within 24 hours prior to the start of treatment;
Note: patients on dialysis will not be eligible

- Group A: hepatic function: normal function (bilirubin =< upper limit of normal
[ULN]; AST =< ULN); renal function: normal function (creatinine clearance [CrCl]
>= 60 mL/min)

- Group B: hepatic function: normal function (bilirubin =< ULN; AST =< ULN); renal
function: moderate dysfunction (CrCl >= 30 and < 60 ml/min)

- Group C: hepatic function: normal function (bilirubin =< ULN; AST =< ULN); renal
function: severe dysfunction (CrCl >= 15 and < 30 ml/min)

- Group D: hepatic function: mild dysfunction D1: bilirubin =< ULN; AST > ULN, D2:
bilirubin > ULN and =< 1.5 x ULN; any AST; renal function: normal function
(creatinine clearance [CrCl] >= 60 mL/min)

- Group E: hepatic function: mooderate dysfunction (bilirubin 1.5 x > ULN and =< 3
x ULN; any AST); renal function: normal function (creatinine clearance [CrCl] >=
60 mL/min)

- Group F: hepatic function: severe dysfunction (bilirubin > 3 x ULN and up to
investigator's discretion; any AST); renal function: normal function (creatinine
clearance [CrCl] >= 60 mL/min)

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
the duration of study participation; should a woman become pregnant or suspect she is
pregnant while she or her partner is participating in this study, she should inform
her treating physician immediately; men treated or enrolled on this protocol must also
agree to use adequate contraception prior to the study, for the duration of study
participation, and 4 months after completion of talazoparib administration

- All prior treatment-related toxicities must be Common Terminology Criteria for Adverse
Events (CTCAE) v4.03 grade =< 1 (except for adverse events [AEs] not considered to be
dose-limiting toxicities [DLTs] in this trial such as alopecia and lymphopenia) at the
time of enrollment; if there are any questions, please contact the study's principal
investigator

- Females of childbearing potential must have a negative serum pregnancy test at
screening

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Prior treatment with talazoparib or a poly(adenosine diphosphate [ADP]-ribosyl)ation
(PARP)1/2 inhibitor; prior treatment with other agents that inhibit deoxyribonucleic
acid (DNA) repair (i.e. WEE1 homolog [S. pombe] [WEE1] inhibitors, ataxia
telangiectasia mutated [ATM] inhibitors), is allowed; if there are any questions,
please contact the study's principal investigator

- Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity,
biologic therapy, or immunotherapy must not be given within 28 days prior to study
enrollment; for daily or weekly chemotherapy without the potential for delayed
toxicity, a washout period of 14 days prior to enrollment may be acceptable, and
questions related to this can be discussed with study principal investigator

- Clinically significant bleeding diathesis or coagulopathy, including known platelet
function disorders

- Known hypersensitivity to any of the components of talazoparib

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to talazoparib

- Use of other investigational drugs within 28 days (or five half-lives, whichever is
shorter; with a minimum of 14 days from the last dose) preceding the first dose of
talazoparib and during the study

- Symptomatic or untreated leptomeningeal or brain metastases or spinal cord
compression; patients with treated central nervous system (CNS) metastasis, no longer
requiring steroid therapy are potentially eligible; patients with primary glioblastoma
multiforme not requiring steroid therapy will be eligible

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, clinically
significant cardiac arrhythmias, or psychiatric illness/social situations that would
limit compliance with study requirements

- Any other known malignancy within 3 years (with the exception of non-melanoma skin
cancer that had undergone curative treatment, cervical cancer in situ, or
ductal/lobular carcinoma in situ of the breast that has underwent local treatment);
consult the Cancer Therapy Evaluation Program (CTEP) medical monitor if unsure whether
second malignancies meet the requirements specified above

- Women of childbearing potential should be advised to avoid pregnancy and use effective
methods of contraception for 4 months after study treatment is completed; men with a
female partner of childbearing potential must have either had a prior vasectomy or
agree to use effective contraception for at least 4 months after study treatment is
completed; if a female patient or a female partner of a patient becomes pregnant while
the patient receives talazoparib, the potential hazard to the fetus should be
explained to the patient and partner (as applicable)

- Active hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (patients with
chronic or cleared HBV and HCV infection are eligible)

- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible

- Any condition or medical problem in addition to the underlying malignancy and organ
dysfunction that the investigator feels would pose unacceptable risk