Ganetespib, Paclitaxel, Trastuzumab and Pertuzumab for Metastatic Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer
HER2-positive Breast Cancer
Male Breast Cancer
Recurrent Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Clinical Trial of Ganetespib (Heat Shock Protein 90 Inhibitor) in Combination With Paclitaxel, Trastuzumab and Pertuzumab in Human Epidermal Growth Factor Receptor-2 Positive (HER2+) Metastatic Breast Cancer|
- Maximum tolerated dose (MTD) and recommended Phase II dose of ganetespib plus paclitaxel plus trastuzumab and pertuzumab [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- Objective Response Rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Defined as the percentage of patients who have achieved complete response or partial response assessed based on Response evaluation criteria in solid tumors 1.1 (RECIST 1.1).
- Clinical benefit rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Defined as the percentage of patients who have achieved complete response, partial response, or stable disease for at least 24 weeks assessed based on RECIST 1.1.
- Duration of response [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]The duration of response is measured from the time of response to disease progression.
- Progression-free survival (PFS) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]The median time of progression-free survival will be calculated.
- PK parameters of paclitaxel (such as area under the curve and maximum concentration) [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 7, 21, 24, 27, and 31 hours ] [ Designated as safety issue: No ]Will be examined descriptively to evaluate the effect of ganetespib on the paclitaxel absorption.
|Study Start Date:||April 2014|
|Estimated Study Completion Date:||June 2017|
|Estimated Primary Completion Date:||June 2017 (Final data collection date for primary outcome measure)|
Experimental: ganetespib, paclitaxel, and trastuzumab with pertuzumab
Patients receive trastuzumab intravenously (IV) over 30 minutes on days 1, 8, 15, and 22, pertuzumab IV over 30 minutes every 3 weeks (only in Part II of the study, starting day 1), paclitaxel IV over 1 hour on days 1, 8, 15, and 22, and ganetespib IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. The MTD for ganetespib in combination with paclitaxel and trastuzumab is 150 mg/m2.
Other Names:Drug: paclitaxel
Other Names:Biological: trastuzumab
Other Names:Biological: pertuzumab
Other Name: Perjeta
This phase I trial studies the side effects and best dose of ganetespib when given with paclitaxel, trastuzumab, pertuzumab in treating patients with human epidermal growth factor receptor 2 positive (HER2+) breast cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or has returned after a period of improvement (metastatic). HER2+ describes cancer cells that have too much of a protein called HER2 on their surface. In normal cells, HER2 helps to control cell growth. When it is made in larger than normal amounts by cancer cells, the cells may grow more quickly and be more likely to spread to other parts of the body.
Ganetespib may stop the growth of tumor cells by blocking some of the proteins needed for cell growth. Drugs used in chemotherapy, such as 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. Monoclonal antibodies, such as trastuzumab and pertuzumab, bind to HER2+ cancer cells and may kill them. Giving ganetespib with paclitaxel, trastuzumab, and pertuzumab may be a better treatment for patients with HER2+ breast cancer.
This phase I study has two parts. During the first part of this study, patients with HER2+ MBC receive trastuzumab in combination with ganetespib and paclitaxel to evaluate the safety, toxicity and maximum tolerated dose (MTD) of this triplet regimen. There are dose escalations for ganetespib. Paclitaxel and trastuzumab are administered at standard doses without escalation. Part 1 is ongoing.
During the second part of this study, pertuzumab at standard dose will be added to the triplet regimen of ganetespib, paclitaxel and trastuzumab, using the MTD of ganetespib determined in part one. The MTD of ganetespib and the safety of the four-drug regimen will be evaluated. The MTD for ganetespib in combination with paclitaxel and trastuzumab is 150 mg/m2.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02060253
|United States, New York|
|NYU Cancer Institute|
|New York, New York, United States, 10016|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Shanu Modi, MD||Memorial Sloan Kettering Cancer Center|