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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02567396
• Date of registration: 02/10/2015
• Prospective Registration: Yes
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Talazoparib in Treating Patients With Advanced or Metastatic Solid Tumors That Cannot Be Removed by Surgery and Liver or Kidney Dysfunction
• Scientific title: A Phase I Study of Single Agent Talazoparib (BMN 673) in Advanced Cancer Patients With Hepatic and Renal Dysfunction
• Date of first enrolment: June 2016
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT02567396
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Canada

Contacts

• Name: Daniel Renouf
• Affiliation: University Health Network Princess Margaret Cancer Center LAO

Key inclusion & exclusion 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
duct


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Hormone-Resistant Prostate Cancer

Metastatic Pancreatic Adenocarcinoma

Stage IIIB Small Cell Lung Carcinoma

Stage IV Non-Small Cell Lung Cancer

Stage IV Ovarian Cancer

Solid Neoplasm

Stage III Mesothelioma

Stage IIIA Non-Small Cell Lung Cancer

Stage IIIB Gastric Cancer

Stage IIIC Gastric Cancer

Stage IIIA Gastric Cancer

Stage IIIA Ovarian Cancer

Stage IV Mesothelioma

Triple-Negative Breast Carcinoma

Head and Neck Squamous Cell Carcinoma

Stage IIIB Ovarian Cancer

Stage IV Small Cell Lung Carcinoma

Estrogen Receptor Negative

Progesterone Receptor Negative

Stage IIIA Small Cell Lung Carcinoma

Stage IIIB Non-Small Cell Lung Cancer

HER2/Neu Negative

Stage IIIC Ovarian Cancer

Intervention(s)

Drug: Talazoparib

Other: Laboratory Biomarker Analysis

Other: Pharmacological Study

Primary Outcome(s)

Recommended phase 2 dose of talazoparib, graded according to NCI CTCAE version 4.0 [Time Frame: Up to 28 days]

Incidence of toxicity, graded according to the National Cancer Institute (NCI) CTCAE version 4.03 [Time Frame: Up to 4 weeks after completion of study treatment]

Tolerability of talazoparib in patients with varying degrees of hepatic and renal dysfunction [Time Frame: Up to 4 weeks after completion of study treatment]

Secondary Outcome(s)

Progression-free survival (PFS) [Time Frame: Up to 4 weeks after completion of study treatment]

Biomarkers associated with response or resistance to talazoparib [Time Frame: Up to 4 weeks after completion of study treatment]

Objective response, graded according to RECIST version 1.1 [Time Frame: Up to 4 weeks after completion of study treatment]

PK profiles of talazoparib in patients with varying degrees of hepatic and renal dysfunction [Time Frame: Pre-dose, and 30 minutes, 1, 2, 4, 6, 8, and 24 hours post-dose on day 1 of course 2, and pre-dose on day 1 of courses 3 and 4]

Response rate [Time Frame: Up to 4 weeks after completion of study treatment]

Secondary ID(s)

9942

UM1CA186644

PJC-022

NCI-2015-01641

Source(s) of Monetary Support

Please refer to primary and secondary sponsors