Clinical trial NCT02060253 (phase 1, status: completed)
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
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60, C50.021, C50.022, C50.029, C50.121, C50.122, C50.129, C50.621, C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60, C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60, C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60, C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60, C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: ganetespib, paclitaxel
SMILES: CC(C)C1=CC(C2=NN=C(O)N2C2=CC=C3N(C)C=CC3=C2)=C(O)C=C1O, [H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](OCCO)[C@@H](C1)OC
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)

          -  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

        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

          -  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