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HER2-positive Breast CancerPhase 1NCT02060253

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

A Phase 1 study testing ganetespib, paclitaxel and trastuzumab in people with HER2-positive Breast Cancer and Male Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ganetespib, paclitaxel and trastuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
2 sitesUnited States
Study dates
Apr 2014to Jun 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • 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+
  • Patients for the triplet regimen (ganetespib, paclitaxel, trastuzumab):
  • 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
  • Patients for the triplet regimen + pertuzumab:
  • Prior hormonal therapy for ER+ and/or PR+ HER2+ disease in the metastatic setting is allowed.
  • Prior T-DM1 in the metastatic setting is allowed if patients have progressed within 6 months after treatment for early-stage disease.
  • 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

Who cannot join

  • 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
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  • 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
  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • NYU Cancer Institute

    New York, New York, 10016

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

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

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).

Read the 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.

Being tested
ganetespib, paclitaxel, trastuzumab, pertuzumab
Medical subject headings
Breast Neoplasms, Male, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ganetespibDrug

    Also called Hsp90 inhibitor STA-9090, STA-9090

    Given IV

  • paclitaxelDrug

    Also called Anzatax, Asotax, TAX, Taxol

    Given IV

  • trastuzumabBiological

    Also called anti-c-erB-2, Herceptin, MOAB HER2

    Given IV

  • pertuzumabBiological

    Also called Perjeta

    Given IV

Study groups in NCT02060253
Study groupRoleWhat they receive
ganetespib, paclitaxel, and trastuzumab with pertuzumabExperimentalPatients 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.
Receives: Drug: ganetespib; Drug: paclitaxel; Biological: trastuzumab; Biological: pertuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 28 days

Secondary outcomes (4)

  1. Objective Response Rate

    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).

    Measured: Up to 2 years

  2. Clinical benefit rate

    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.

    Measured: Up to 2 years

  3. Duration of response

    The duration of response is measured from the time of response to disease progression.

    Measured: Up to 2 years

  4. Progression-free survival (PFS)

    The median time of progression-free survival will be calculated.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2014 (estimated)
  2. Study startApr 2014
  3. Primary completionJun 2018
  4. Study completionJun 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02060253
Sponsor's protocol ID
13-168
Status last verified
Jun 2018
First submitted
30 Jan 2014
Last updated
14 Jun 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 28764748

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ganetespib, paclitaxel and trastuzumab in people with HER2-positive Breast Cancer and Male Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) and recommended Phase II dose of ganetespib plus paclitaxel plus trastuzumab and pertuzumab (time frame: 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02060253, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2018; AzTrials last refreshed its copy on 8 Nov 2026.

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