Galunisertib and Paclitaxel in Treating Patients With Metastatic Androgen Receptor Negative (AR-) Triple Negative Breast Cancer
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|ClinicalTrials.gov Identifier: NCT02672475|
Recruitment Status : Recruiting
First Posted : February 3, 2016
Last Update Posted : October 23, 2018
|Condition or disease||Intervention/treatment||Phase|
|Estrogen Receptor Negative HER2/Neu Negative Progesterone Receptor Negative Recurrent Breast Carcinoma Stage IV Breast Cancer Triple-Negative Breast Carcinoma||Drug: Galunisertib Other: Laboratory Biomarker Analysis Drug: Paclitaxel||Phase 1|
I. To assess the safety and tolerability of paclitaxel when administered with LY2157299 (Galunisertib).
II. To determine the maximally tolerated dose (MTD) of paclitaxel + LY2157299. III. To determine the recommended dose of paclitaxel with LY2157299 for phase II studies.
I. To evaluate the efficacy, as measured by median progression free survival (PFS), of paclitaxel + LY2157299 in patients with metastatic androgen receptor negative triple negative metastatic breast cancer.
II. To evaluate the efficacy, as measured by clinical benefit rate (CBR), of paclitaxel + LY2157299 in patients with androgen receptor negative metastatic triple negative metastatic breast cancer.
III. To determine the overall response rate (ORR) of paclitaxel + LY2157299 in patients with androgen receptor negative metastatic triple negative breast cancer.
I. To interrogate the entire coding sequence of 236 cancer-related genes (3,769 exons) plus 47 introns from 19 genes often rearranged or altered in cancer.
II. Nanostring analysis of established gene expression signatures. III. Determine breast cancer subtype by PAM50 testing and correlate with response.
IV. To measure changes in circulating plasma transforming growth factor beta 1 (TGFB1), interleukin (IL)-6, and cluster of differentiation 34 (CD34) positive (+), peripheral blood mononuclear cells (PBMCs) induced by LY2157299.
OUTLINE: This is a dose-escalation study of Galunisertib.
Patients receive paclitaxel intravenously (IV) on days 1, 8, and 15. Patients also receive Galunisertib orally (PO) twice daily (BID) on days 1-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||29 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib Trial of LY2157299 (TGFβR1 Kinase Inhibitor) With Paclitaxel in Patients With Triple Negative Metastatic Breast Cancer|
|Study Start Date :||March 2016|
|Estimated Primary Completion Date :||January 2020|
|Estimated Study Completion Date :||June 2021|
Experimental: Treatment (Paclitaxel, Galunisertib)
Patients receive Paclitaxel IV on days 1, 8, and 15. Patients also receive GalunisertibPO BID on days 1-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Incidence of adverse events [ Time Frame: Up to 28 days after last dose of study treatment ]Adverse events will be classified by type, incidence, severity and causality. All adverse events will be summarized by patient and dose level.of galunisertib in combination with paclitaxel graded by National Cancer Institute Common Terminology Criteria For Adverse Events (NCI CTCAE) version 4.03
- Maximum Tolerated Dose (MTD) of paclitaxel + LY2157299 [ Time Frame: Up to 28 days ]MTD is defined as the highest dose tested in which a dose limiting toxicity is experienced by 0 out of 3 or 1 out of 6 patients among the dose levels galunisertib in combination with paclitaxel graded by NCI CTCAE version 4.03
- Overall Response Rate (ORR) [ Time Frame: On‐treatment date to date of disease progression, assessed up to 3 years ]Number of patients in each response category, per RECIST v1.1, summarized as follows for target lesion criteria complete response (CR),disappearance of target lesions; partial response (PR), >=30% decrease in sum of longest diameter of target lesions; progressive disease (PD), >=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or SD. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR>PR>SD>PD.
- Progression-Free Survival (PFS) [ Time Frame: On‐study date to lesser of date of progression or date of death from any cause, assessed up to 3 years ]Estimated probable duration of life without disease progression, from on‐study date to earlier of progression date or date of death from any cause, using the Kaplan‐Meier method with censoring. Disease progression is defined under RECIST v1.1 as >=20% increase in sum of longest diameters of target lesions, unequivocal progression of non‐target lesions, or appearance of new lesions.
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): NCT02672475
|Contact: VICC Clinical Trials Information Program||800-811-8480|
|United States, Tennessee|
|Vanderbilt University/Ingram Cancer Center||Recruiting|
|Nashville, Tennessee, United States, 37232|
|Contact: G. VICC Clinical Trials Information Program 800-811-8480|
|Principal Investigator: Vandana G. Abramson, MD|
|Principal Investigator:||Vandana Abramson, MD||Vanderbilt University/Ingram Cancer Center|