| Eligibility |
Inclusion Criteria:
- Adult patients with solid tumors and documented germline or somatic aberrations in
genes involved in DNA damage response (DDR) and whose disease has progressed following
at least one standard therapy or who have no acceptable standard treatment options.
Molecular testing performed at an National Cancer Institute-Molecular Analysis for
Therapy Choice (NCI-MATCH) (NCT02465060) study-designated Clinical Laboratory
Improvement Act (CLIA) laboratory or at Myriad Genetics, GeneDx, Invitae, or the
Frederick National Laboratory for Cancer Research (FNLCR) Molecular Characterization
Laboratory (MoCha) will be acceptable for determination of eligibility
- Patients with the following germline or somatic genetic aberrations will be eligible
based on compelling preclinical and/or clinical data suggesting that these deleterious
mutations confer sensitivity to PARP inhibitors; no more than 6 patients (across both
cohorts) with an eligibility mutation in any one gene will be enrolled
- Deleterious BRCA1 or BRCA2 mutations
- Loss of function mutations (including novel loss of function frameshift or
nonsense mutations) in the following Fanconi anemia genes: FANCA, FANCB, FANCC,
FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN
- A known functional mutation (including novel loss of function frameshift or
nonsense mutations) in any of the following DDR genes: ARID1A, ATM, ATR, BACH1
(BRIP1), BAP1, BARD1, CDK12, CHK1, CHK2, IDH1, IDH2, MRE11A, NBN, PALB2, RAD50,
RAD51, RAD51B, RAD51C, RAD51D, RAD54L
- Age >= 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Life expectancy of greater than 3 months
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Hemoglobin >= 10 g/dL
- Total bilirubin =< 1.5 x institutional upper limit of normal (=< 3 x upper limit of
normal in the presence of documented Gilbert's syndrome or liver metastases at
baseline)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) /
alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x
institutional upper limit of normal
- Creatinine =< 1.5 x institutional upper limit of normal OR Creatinine clearance (CrCl)
>= 60 mL/min/1.73m^2 unless data exists supporting safe use at lower kidney function
values, no lower than 30 mL/min/1.73m^2
- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded for
non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest
x-ray or as >= 10 mm (>= 1 cm) with computed tomography (CT) scan, magnetic resonance
imaging (MRI), or calipers by clinical exam
- Patients must have a tumor site amenable to biopsy. If avoidable, the lesion for
biopsy should not be selected as a target lesion for RECIST measurements
- The effects of talazoparib on the developing human fetus are unknown. For this reason
and because PARP inhibitors are known to be teratogenic, women of child-bearing
potential must agree to use a highly effective method of contraception for the
duration of study participation and for at least 7 months after completing study
treatment. 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. Male patients with female partners of reproductive potential and pregnant
partners who are treated or enrolled on this protocol must also agree to use adequate
contraception for the duration of study participation and for at least 4 months after
completion of talazoparib administration
- Patients must be able to swallow whole tablets or capsules. Nasogastric or
gastric-tube (G-tube) administration is not allowed. Any gastrointestinal disease
which would impair ability to swallow, retain, or absorb drug is not allowed
- Ability to understand and the willingness to sign a written informed consent document
- Patients must have recurrent, locally advanced or metastatic disease
- Patients must have progressed on or after at least one line of standard-of-care (SOC)
intervention, except for those patients without SOC or for whom talazoparib is SOC
- PATIENTS WITH OVARIAN CANCER:
- All patients with ovarian cancer should have one prior platinum-based therapy
- Patients with ovarian cancer with platinum-sensitive disease are eligible. Patients
with platinum-refractory disease are not eligible
- Patients with gBRCAm ovarian cancer must also have progressed on a PARP inhibitor. The
time and treatment between the prior PARP inhibitor and protocol initiation must be
documented
- PATIENTS WITH PANCREATIC CANCER:
- All patients with pancreatic cancer should have received prior platinum-containing
therapy
- PATIENTS WITH BREAST CANCER:
- Patients with HER2+ breast cancer should have had 2 prior systemic lines of therapy in
the metastatic setting, including anti-HER2 therapy
- Patients with breast cancer who are eligible for a PARP inhibitor by Food and Drug
Association (FDA) approvals must have had prior PARP inhibitor as per FDA indication.
The time and treatment between the prior PARP inhibitor and protocol initiation must
be documented
- PATIENTS WITH GASTRIC CANCER:
- Patients with HER2+ gastric cancer should have had received anti-HER2 therapy in the
metastatic setting
- PATIENTS WITH PROSTATE CANCER:
- Patients with prostate cancer who are eligible for a PARP inhibitor by FDA approvals
must have had prior PARP inhibitor for eligibility. The time and treatment between the
prior PARP inhibitor and protocol initiation must be documented
- All patients with prostate cancer can continue to receive treatment with
gonadotropin-releasing hormone (GnRH) agonists while on study, as long as there is
evidence of disease progression on prior therapy
- Patients with castration resistant prostate cancer must have castrate levels of
testosterone (< 50 ng/dL [1.74 nmol/L])
- Patients with metastatic hormone receptor (HR) prostate cancer and mutations in either
BRCA1, BRCA2, or ATM should continue to receive anti-AR therapy
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 4 weeks or 5 half-lives,
whichever is shorter (6 weeks for nitrosoureas or mitomycin C). Patients must be >= 2
weeks since any prior administration of a study drug in a phase 0 or equivalent study
and be >= 1 week from palliative radiation therapy. Patients must have recovered to
eligibility levels from prior toxicity or adverse events
- Patients who have had prior treatment with talazoparib are ineligible
- Patients who have had prior monoclonal antibody therapy must have completed that
therapy >= 6 weeks (or 3 half-lives of the antibody, whichever is shorter) prior to
enrollment on protocol (minimum of 1 week between prior therapy and study enrollment)
except for monoclonal antibody therapies that have been proven to be safe when
combined with PARP inhibitor (PARPi) treatment (such as anti-PD-1/PD-L1 and
anti-HER2), which must be completed >= 4 weeks prior to enrollment
- Patients who are receiving any other investigational agents
- Patients with active brain metastases or carcinomatous meningitis are excluded from
this clinical trial. Patients with treated brain metastases, whose brain metastatic
disease has remained stable for >= 1 month without requiring steroid and anti-seizure
medication are eligible to participate
- Eligibility of subjects receiving any medications or substances with the potential to
affect the activity or pharmacokinetics of talazoparib will be determined following
review by the principal investigator
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements
- Pregnant women are excluded from this study because the effects of the study drugs on
the developing fetus are unknown
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
- Patients who require use of coumarin-derivative anticoagulants such as warfarin are
excluded. Low-dose warfarin (=< 1 mg/day) is permitted
- Women who are currently lactating
- History of prior malignancies within the past 3 years other than non-melanomatous skin
cancers that have been controlled
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