Talazoparib and HSP90 Inhibitor AT13387 in Treating Patients With Metastatic Advanced Solid Tumor or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple Negative Breast Cancer
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|ClinicalTrials.gov Identifier: NCT02627430|
Recruitment Status : Withdrawn (Other - Protocol moved to Withdrawn)
First Posted : December 11, 2015
Last Update Posted : July 26, 2016
|Condition or disease||Intervention/treatment||Phase|
|Adult Solid Neoplasm Estrogen Receptor Negative Fallopian Tube Serous Neoplasm HER2/Neu Negative Ovarian Serous Adenocarcinoma Ovarian Serous Tumor Primary Peritoneal Serous Adenocarcinoma Progesterone Receptor Negative Recurrent Breast Carcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Triple-Negative Breast Carcinoma||Drug: Hsp90 Inhibitor AT13387 Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Talazoparib||Phase 1|
I. To establish the maximum tolerated dose (MTDs) of BMN673 (talazoparib) and AT13387 (HSP90 Inhibitor AT13387) administered in combination in patients with advanced solid tumors.
I. To identify the dose-limiting toxicity (DLT) and other toxicities associated with BMN673 and AT13387 administered in combination as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0.
II. To determine the recommended phase 2 doses (RP2D) of the combination of BMN673 and AT13387.
III. To determine the plasma pharmacokinetics of BMN673 and AT13387. IV. To document anti-tumor activity of the combination of BMN673 and AT13387 as assessed by (Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and progression free survival (PFS).
OUTLINE: This is a dose-escalation study.
Patients receive talazoparib orally (PO) once daily (QD) on days 1-7 (course 0). Beginning in course 1, patients receive talazoparib PO QD on days 1-28 and HSP90 inhibitor AT13387 intravenously (IV) over 1 hour on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days and then every 3 months for up to 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of PARP Inhibitor BMN 673 and HSP90 Inhibitor AT13387 for Treatment of Advanced Solid Tumors With Expansion in Patients With Recurrent Epithelial Ovarian, Fallopian Tube, Peritoneal Cancer or Recurrent Triple-Negative Breast Cancer|
|Study Start Date :||March 2016|
|Estimated Primary Completion Date :||March 2019|
Experimental: Treatment (talazoparib and Hsp90 inhibitor AT13387)
Patients receive talazoparib PO QD on days 1-7 (course 0). Beginning in course 1, patients receive talazoparib PO QD on days 1-28 and HSP90 inhibitor AT13387 IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Hsp90 Inhibitor AT13387
Other Name: AT13387
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- MTD based on the dose-limiting toxicity based on the National Cancer Institute (NCI) CTCAE v. 4.0 [ Time Frame: 35 days ]DLT defined as non-hematologic and hematologic toxicities experienced during course 0 and the first course (i.e. first 4 weeks) of treatment.
- Incidence of adverse events as assessed by NCI CTCAE v. 4.0 [ Time Frame: 30 days post-treatment ]
- Pharmacokinetic (PK) parameters of talazoparib and HSP90 inhibitor AT13387 [ Time Frame: Baseline, at 1, 2, 4 and 8 hours of day 1 (course 0), baseline of days 1, 8, and 15 of course 1, and at 1, 2, 4, and 8 hours post-dosing on day 8 and 15 of course 1 ]Pearson correlation coefficients, presented with 95% confidence intervals, will be used to investigate the association of the percent change heat shock protein 90 and poly(adenosine diphosphate-ribose) polymerase 1 activities with PK parameters, including maximum concentration observed and area under the curve.
- Change in BRCA1 foci expression in tumor tissue via IHC [ Time Frame: Baseline to day 15 of course 1 ]Paired t-tests will be used to compare BRCA1 foci formation following BMN673/AT13387.
- Change in BRCA1 foci expression in tumor tissue via immunohistochmestry (IHC) [ Time Frame: Baseline to day 7 of course 0 ]Paired t-tests will be used to compare BRCA1 foci formation following BMN673.
- Change in heat shock protein 70 (HSPT70) expression [ Time Frame: Day 7 (course 0) to day 15 (course 1) ]Changes in parameters of HSP70 activities that occur post-treatment will be summarized using descriptive statistics.
- Change in RAD51 foci expression in tumor tissue via IHC [ Time Frame: Baseline to day 15 of course 1 ]Paired t-tests will be used to compare RAD51 foci formation following BMN673/AT13387.
- Change in RAD51 recombinase (RAD51) foci expression in tumor tissue via IHC [ Time Frame: Baseline to day 7 of course 0 ]Paired t-tests will be used to compare RAD51 foci formation following BMN673.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02627430
|Principal Investigator:||Panagiotis Konstantinopoulos||Dana-Farber - Harvard Cancer Center LAO|