Ganetespib, Paclitaxel, Trastuzumab and Pertuzumab for Metastatic Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer

NCT02060253 | Completed Phase 1 DMC

• 1 other identifier: 13-168
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) and recommended Phase II dose of ganetespib plus paclitaxel plus trastuzumab and pertuzumab

  28 days

Secondary Outcomes (4)

• 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

Other Outcomes (1)

• PK parameters of paclitaxel (such as area under the curve and maximum concentration)

  Pre-dose, 0.5, 1, 1.5, 2, 4, 7, 21, 24, 27, and 31 hours

Study Arms (1)

ganetespib, paclitaxel, and trastuzumab with pertuzumab

EXPERIMENTAL

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.

Drug: ganetespib; Drug: paclitaxel; Biological: trastuzumab; Biological: pertuzumab

Interventions

ganetespib DRUG

Given IV

Also known as: Hsp90 inhibitor STA-9090, STA-9090

ganetespib, paclitaxel, and trastuzumab with pertuzumab

paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, TAX, Taxol

ganetespib, paclitaxel, and trastuzumab with pertuzumab

trastuzumab BIOLOGICAL

Given IV

Also known as: anti-c-erB-2, Herceptin, MOAB HER2

ganetespib, paclitaxel, and trastuzumab with pertuzumab

pertuzumab BIOLOGICAL

Given IV

Also known as: Perjeta

ganetespib, paclitaxel, and trastuzumab with pertuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
• Albumin ≥ 3.0 g/dL
• Adequate renal function as defined by a serum creatinine ≤ 1.5 x ULN
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
• Female subjects of childbearing potential and males must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) for the duration of study treatment

You may not qualify if:

• 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
• Adverse events related to trastuzumab, murine proteins, or any of the excipients that resulted in trastuzumab being permanently discontinued
• History of severe (grade 3 or 4) allergic or hypersensitivity reactions to excipients (e.g., polyethylene glycol \[PEG\] 300 and polysorbate 80)
• History of intolerance or hypersensitivity to paclitaxel and/or adverse events related to paclitaxel that resulted in paclitaxel being permanently discontinued
• Peripheral neuropathy of grade \>= 2 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, at the time of or within 3 weeks prior to the first study therapy
• Baseline QTc \> 470 msec (average of triplicate ECG recordings); a consistent method of QTc calculation must be used for each patient's QTc measurements. QTcF (Fridericia's formula) is preferred

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Synta Pharmaceuticals Corp.: collaborator
• New York University Cancer Institute: collaborator

Study Sites (2)

NYU Cancer Institute

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Jhaveri K, Wang R, Teplinsky E, Chandarlapaty S, Solit D, Cadoo K, Speyer J, D'Andrea G, Adams S, Patil S, Haque S, O'Neill T, Friedman K, Esteva FJ, Hudis C, Modi S. A phase I trial of ganetespib in combination with paclitaxel and trastuzumab in patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer. Breast Cancer Res. 2017 Aug 2;19(1):89. doi: 10.1186/s13058-017-0879-5.

  PMID: 28764748 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Breast Neoplasms, Male; Breast Neoplasms

Interventions

STA 9090; Paclitaxel; Taxes; Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Shanu Modi, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2014
• First Posted: February 12, 2014
• Study Start: April 1, 2014
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: June 14, 2018

Record last verified: 2018-06

Locations

US (2)