Ganetespib, Paclitaxel and Trastuzumab for Advanced or Metastatic Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by New York University School of Medicine
Sponsor:
Collaborators:
Synta Pharmaceuticals Corp.
Memorial Sloan-Kettering Cancer Center
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT02060253
First received: January 30, 2014
Last updated: June 4, 2014
Last verified: June 2014
  Purpose

This phase I trial studies the side effects and best dose of ganetespib when given with paclitaxel and trastuzumab in treating patients with advanced or metastatic human epidermal growth factor receptor 2 positive (HER2+) breast cancer. 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. Checking to see if a cancer is HER2+ may help plan treatment, which may include drugs that kill HER2+ cancer cells. Ganetespib may stop the growth of tumor cells by blocking some of the enzymes 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 or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block the ability of tumors to grow and spread. Giving ganetespib with paclitaxel and trastuzumab may be an effective treatment for patients with HER2+ breast cancer.


Condition Intervention Phase
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
Drug: ganetespib
Drug: paclitaxel
Biological: trastuzumab
Phase 1

Study Type: Interventional
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 and Trastuzumab in Human Epidermal Growth Factor Receptor-2 Positive (HER2+) Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of ganetespib when combined with paclitaxel and trastuzumab [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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.


Estimated Enrollment: 18
Study Start Date: April 2014
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ganetespib, paclitaxel, and trastuzumab
Patients receive trastuzumab IV over 30 minutes on days 1, 8, 15, and 22, paclitaxel IV over 1 hour on days 1, 8, 15, and 22, and ganetespib intravenously (IV) over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Drug: ganetespib
Given IV
Other Names:
  • Hsp90 inhibitor STA-9090
  • STA-9090
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Biological: trastuzumab
Given IV
Other Names:
  • anti-c-erB-2
  • Herceptin
  • MOAB HER2

Detailed Description:

PRIMARY OBJECTIVES:

I. To establish the safety, tolerability, maximum tolerated dose (MTD) and the recommended phase II dose of ganetespib plus paclitaxel in conjunction with trastuzumab in patients with HER2+ metastatic breast cancer (MBC).

SECONDARY OBJECTIVES:

I. To evaluate the possible effects of ganetespib on the pharmacokinetics (PK) of paclitaxel.

II. To make a preliminary assessment of the efficacy of the combination of ganetespib, paclitaxel and trastuzumab as measured by objective response rate (ORR), progression-free survival (PFS), duration of response, and clinical benefit rate (complete response + partial response + stable disease > 24 weeks).

OUTLINE:

Patients receive trastuzumab IV over 30 minutes on days 1, 8, 15, and 22, paclitaxel IV over 1 hour on days 1, 8, 15, and 22, and ganetespib intravenously (IV) over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
  • Albumin >= 3.0 g/dL
  • 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
  • Female subjects of childbearing age must have a negative serum pregnancy test at study entry
  • Patients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) are allowed on study if they have an undetectable viral load, cluster of differentiation (CD)4 > 300 and are on a stable highly active antiretroviral therapy (HAART) regimen for 1 month prior to study enrollment
  • Patients are required to have HER2+ breast cancer defined as a fluorescent in situ hybridization (FISH)- ratio of >= 2.0 or immunohistochemistry (IHC) 3+
  • Any number of prior chemotherapies or biological therapies are allowed, patients are required to have prior treatment with pertuzumab and ado-trastuzumab emtansine with the exceptions listed below:

    • Metastatic patients who have not received prior pertuzumab are eligible if: heavily pretreated prior to Food and Drug Administration (FDA) approval of pertuzumab (08-Jun-2012) for first line treatment of HER2+ MBC
    • Metastatic patients who have not received ado-trastuzumab emtansine are eligible if: heavily pretreated prior to FDA approval of ado-trastuzumab emtansine (22-Feb-2013) for the treatment of patients with HER2+ MBC who previously received trastuzumab and a taxane, separately or in combination
  • No prior history of intolerance or hypersensitivity to trastuzumab and/or adverse events related to trastuzumab, murine proteins, or any of the excipients that resulted in trastuzumab being permanently discontinued

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
  • 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
  • Use of medications that have been linked to the occurrence of torsades de pointes

    • Patients will be eligible for the study if they discontinue any of the listed medications two weeks prior to registration and study enrollment
    • Stable regimen of antidepressants of the SSRI class is allowed (common SSRIs include escitalopram oxalate, citalopram, fluvoxamine, paroxetine, sertraline and fluoxetine)
  • Left ventricular ejection fraction (EF) < 50% at baseline
  • Serum potassium, magnesium, and calcium levels (corrected for albumin) outside the laboratory's reference range despite correction
  • Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation)
  • Women who are pregnant or lactating
  • Current known active infection with HIV, hepatitis B or C viruses
  • Uncontrolled systemic disease (e.g., clinically significant cardiac, pulmonary or metabolic disease)
  • Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results in the judgment of the investigator
  • History of clinically significant cardiac dysfunction, including:

    • Unstable angina
    • Unstable atrial fibrillation
    • Symptomatic bradycardia
    • Indwelling temporary pacemaker
    • History of MI within 6 months prior to first study treatment
    • History of symptomatic CHF (grade > 3 by NCI CTCAE or Class > II by New York Heart Association (NYHA) criteria
    • Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a Class 1a antiarrhythmic drug (eg quinidine, procainamide, disopyramide) or Class III antiarrhythmic drug (eg sotalol, amiodarone, dofetilide). Use of other antiarrhythmic drugs is permitted
    • Second or third degree atrioventricular (AV) block unless treated with a permanent pacemaker
    • Complete left bundle branch block (LBBB)
    • History of long QT syndrome or a family member with this condition
  • Brain metastases that are:

    • Progressive or
    • Have required any type of therapy (including radiation, surgery or steroids) to control symptoms from brain metastases within 60 days prior to the first study treatment
  • History of an invasive second primary malignancy diagnosed within the previous 3 years, except for appropriately treated stage I endometrial or cervical carcinoma or prostate carcinoma treated surgically, and non-melanoma skin cancer
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02060253

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Shanu Modi    646-888-5243    modis@mskcc.org   
Principal Investigator: Shanu Modi         
NYU Cancer Institute Recruiting
New York, New York, United States, 10016
Contact: Komal Jhaveri    212-731-5835    Komal.Jhaveri@nyumc.org   
Principal Investigator: Komal Jhaveri         
Sponsors and Collaborators
New York University School of Medicine
Synta Pharmaceuticals Corp.
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Komal Jhaveri New York University School of Medicine
  More Information

No publications provided

Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT02060253     History of Changes
Other Study ID Numbers: NYU S12-03732, NCI-2014-00177, P30CA016087
Study First Received: January 30, 2014
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Trastuzumab
Mitogens
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 16, 2014