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
Overview
- Phase
- Phase 1
- Intervention
- ganetespib
- Conditions
- HER2-positive Breast Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 9
- Locations
- 2
- Primary Endpoint
- Maximum tolerated dose (MTD) and recommended Phase II dose of ganetespib plus paclitaxel plus trastuzumab and pertuzumab
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
This phase I trial studies the side effects and best dose of ganetespib when given with paclitaxel, trastuzumab and pertuzumab in treating patients with human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (MBC).
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Pathologically confirmed diagnosis of breast cancer (central confirmation is not required)
- •Patients must be at least 18 years of age
- •Metastatic or advanced breast cancer that is evaluable OR metastatic or advanced breast cancer that is measurable for response as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Life expectancy of at least 3 months as assessed by the investigator
- •Patients with estrogen receptor (ER)+ breast cancer must have received prior treatment with at least one hormone therapy
- •Absolute neutrophil count ≥ 1,500 cells/uL
- •Platelets ≥ 100,000/uL
- •Hemoglobin ≥ 9.0g/dL
- •Total bilirubin ≤ 1.5 x the upper limit of normal (ULN)
Exclusion Criteria
- •Fewer than 21 days since last anti-tumor therapy, including chemotherapy, biologic except trastuzumab, experimental, immune, radiotherapy for the treatment of breast cancer, with the following exceptions:
- •Hormone therapy
- •Palliative radiation therapy involving =\< 25% of marrow-bearing bone is allowed if completed within \>= 14 days prior to first study treatment
- •Surgery, radiotherapy, or lesion ablative procedure to the only area of measurable/evaluable disease
- •Major surgery within 4 weeks prior to first dose of ganetespib
- •Poor venous access for study drug administration
- •Study drug administration via indwelling catheters is allowed only if the catheter is made of silicone material
- •No prior chemotherapy in the metastatic setting is allowed.
- •Prior pertuzumab is not allowed in the metastatic setting. Pertuzumab given in the neoadjuvant and/or adjuvant setting is allowed.
- •History of intolerance or hypersensitivity to trastuzumab and/or pertuzumab
Arms & Interventions
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.
Intervention: ganetespib
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.
Intervention: paclitaxel
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.
Intervention: trastuzumab
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.
Intervention: pertuzumab
Outcomes
Primary Outcomes
Maximum tolerated dose (MTD) and recommended Phase II dose of ganetespib plus paclitaxel plus trastuzumab and pertuzumab
Time Frame: 28 days
Secondary Outcomes
- Objective Response Rate(Up to 2 years)
- Clinical benefit rate(Up to 2 years)
- Duration of response(Up to 2 years)
- Progression-free survival (PFS)(Up to 2 years)