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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02317874
Other study ID # NCI-2014-02474
Secondary ID NCI-2014-02474NC
Status Completed
Phase Phase 1
First received
Last updated
Start date September 8, 2015
Est. completion date May 3, 2022

Study information

Verified date August 2023
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This phase I trial studies the side effects and best dose of talazoparib when given together with carboplatin and paclitaxel in treating patients with solid tumors that have spread to other places in the body (advanced) or cannot be removed by surgery. Talazoparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving talazoparib with carboplatin and paclitaxel may kill more tumor cells.


Description:

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Study Design


Related Conditions & MeSH terms

  • Advanced Malignant Solid Neoplasm
  • Metastatic Malignant Solid Neoplasm
  • Neoplasms
  • Unresectable Malignant Solid Neoplasm

Intervention

Drug:
Carboplatin
Given IV
Paclitaxel
Given IV
Talazoparib
Given PO

Locations

Country Name City State
United States Ohio State University Comprehensive Cancer Center Columbus Ohio
United States University of Wisconsin Carbone Cancer Center Madison Wisconsin
United States Rutgers Cancer Institute of New Jersey New Brunswick New Jersey

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Maximum concentration levels from plasma samples Maximum concentration levels will be summarized in terms of means, standard deviations and ranges. Linear mixed effects modeling with subject specific random effects will be performed to evaluate maximum concentration and plasma concentration collected on day 1 and day 3 predict changes in peripheral blood mononuclear cells. Furthermore, the empirical Bayesian approach will be utilized to incorporate pharmacokinetic data from other phase I studies of the agent to construct a pharmacokinetic population model. Pre-dose, 2 hours, and 4 hours after talazoparib administration on days 1 and 3 or 7 (depending on assigned schedule) of cycle 1 and day 1 of cycle 1
Other Changes in peripheral blood mononuclear cell levels Changes in peripheral blood mononuclear cell levels from the cycle 1, day 1 (prior to first talazoparib dose) assessment to the cycle 1, day 3 or 7 and cycle 2, day 1 assessments will be evaluated using a two-sample t-test. Cycle 1 day 1 to cycle 2 day 1
Other Changes in mutation status The number and frequency of mutation status changes from the baseline biopsy assessment to the biopsy obtained at the time of progression will be summarized in tabular format. The frequency of mutation status changes will be analyzed using a paired t-test or nonparametric Wilcoxon Signed Rank test. A negative binomial regression model will be utilized to account for the dose effect. The presence of individual mutations will be compared between the baseline and time of progression assessment using a paired McNemar's test. The Benjamini-Hochberg method will also be utilized. Baseline to time of progression (up to 4 weeks after last dose of treatment)
Primary Maximum tolerated dose and recommended phase 2 dose of talazoparib three day schedule Defined as the highest safely tolerated dose where 0/6 or 1/6 (less than 33%) patients experience a dose-limiting toxicity and two or more patients have experienced a dose-limiting toxicity at the next higher dose level. Adverse events will be evaluated by type and severity using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 until March 31, 2018. CTCAE version 5.0 will be utilized beginning April 1, 2018. Adverse events data collection include adverse event diagnosis, date of onset and resolution, whether the event is ongoing, CTCAE grade, whether the event is serious, frequency, and outcome status, and action taken. 21 days
Primary Maximum tolerated dose and recommended phase 2 dose of talazoparib seven day schedule Defined as the highest safely tolerated dose where 0/6 or 1/6 (less than 33%) patients experience a dose-limiting toxicity and two or more patients have experienced a dose-limiting toxicity at the next higher dose level. Adverse events will be evaluated by type and severity using the National Cancer Institute CTCAE version 4.0 until March 31, 2018. CTCAE version 5.0 will be utilized beginning April 1, 2018. Adverse events data collection include adverse event diagnosis, date of onset and resolution, whether the event is ongoing, CTCAE grade, whether the event is serious, frequency, and outcome status, and action taken. 21 days
Secondary Incidence of toxicity Graded according to NCI CTCAE version 4.0 until March 31, 2018. CTCAE version 5.0 will be utilized beginning April 1, 2018. Toxicities observed will be summarized in terms of types and severities for each schedule and dose level separately. The number and severity of toxicity incidents will be analyzed descriptively in tabular format. Comparisons between dose level arms will be performed using Fisher's exact test. Ninety percent confidence intervals for dose-limiting toxicity rates will be constructed for dose levels with 6 or more patients. Up to 4 weeks after last dose of treatment
Secondary Anti-tumor response Will be determined by Response Evaluation Criteria in Solid Tumors criteria. Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease, stratified by treatment schedule. 90% confidence intervals for the proportions of subjects with a confirmed anti-tumor response will be computed for dose levels with 6 or more patients. Exact logistic regression analysis will be performed to evaluate the dose-response relationship. Chi-square or Fisher's exact test will be used to compare responses between treatment schedules. Up to 4 weeks after last dose of treatment
Secondary Pharmacokinetic parameters (area under the curve and concentration) in plasma samples All pharmacokinetic parameters will be summarized by treatment schedule dose level using standard descriptive statistics: means, medians, ranges, and standard deviations (if numbers and distribution permit). The Jonckheere-Terpstra trend test will be performed to determine the significance of the association between increasing dose level and each of the pharmacokinetic parameters within each treatment schedule. A Spearman rank correlation analysis will be performed to determine the relationship between actual dose administered and the pharmacokinetic parameters. Pre-dose and 4 hours after talazoparib administration on days 1 and 3 or 7 (depending on assigned schedule) of cycle 1 and 0 and 4 hours on day 1 of all subsequent cycles
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