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A Phase II Clinical Trial of 17-Allyamino-17-Demethoxygeldanamycin (17-AAG) in Chemotherapy Refractory Metastatic Breast Cancer

Phase 2
18 Years
Not Enrolling
Recurrent Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer

Thank you

Trial Information

A Phase II Clinical Trial of 17-Allyamino-17-Demethoxygeldanamycin (17-AAG) in Chemotherapy Refractory Metastatic Breast Cancer


I. To determine the response rate of 17-Allylamino-17-Demethoxygeldanamycin (17-AAG)
(tanespimycin) in patients with refractory/resistant metastatic breast cancer.

II. To determine the progression free survival (PFS) of patients with refractory/resistant
metastatic breast cancer when treated with 17-AAG.

III. To correlate patients' her2/neu status with response to 17-AAG treatment.

OUTLINE: This is a multicenter study.

Patients receive tanespimycin IV over 1-6 hours on days 1, 4, 8, and 11. Courses repeat
every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed at day 30, every 10-12 weeks until disease progression, and then every
3 months thereafter.

Inclusion Criteria:

- Primary adenocarcinoma of the breast confirmed by histology or cytology

- Locally advanced or metastatic disease not amenable to surgery or radiation therapy
with curative intent

- At least 1 measurable (target) lesion (i.e. any malignant tumor mass that can be
accurately measured in at least 1 dimension of >= 2 cm with conventional radiographic
techniques or >= 1 cm with magnetic resonance imaging [MRI] or spiral computerized
tomography [CT] scans), not previously irradiated

- Progressive disease following hormonal therapy in appropriate patients (ER-positive
and/or indolent disease)

- Progressive disease following treatment with both an anthracycline and a taxane (as
adjuvant therapy or for metastatic disease) or contraindication to such treatment

- All previous cytotoxic chemotherapy must have been discontinued at least 4 weeks
before study entry and all acute toxicity of prior therapy (excluding alopecia and
neurotoxicity) must be resolved to NCI CTC (Version 3.0) grade =< 1; patients must
have discontinued treatment with nitrosoureas or mitomycin C at least 6 weeks prior
to study entry

- All previous hormonal therapy must have been discontinued for at least 2 weeks before
study entry

- Life expectancy of >= 3 months

- ECOG performance status (PS) of 0-2

- Absolute neutrophil count (ANC) >= 1500/mm^3

- Platelets >= 100,000/mm^3

- Hemoglobin >= 9.0 g/dL

- Creatinine (Cr) =< upper limit of normal (ULN) or Cr Clearance > 60 mL/min/m^2

- Total bilirubin =< 1.5X ULN

- Alanine aminotransferase (ALT) =< 1.5X ULN or =< 3X ULN with liver metastases

- Aspartate aminotransferase (AST) =< 5X ULN or =< 3X ULN with liver metastases

- Negative serum pregnancy test within 7 days of enrollment for pre-menopausal women or
women within 6 months of menopause

- Willingness and ability to comply with scheduled visits, treatment plan, laboratory
tests, and other study procedures

- Evidence of a personally signed and dated informed consent document indicating that
the patient (or a legally acceptable representative) has been informed and
understands all pertinent aspects and the investigational nature of the trial

Exclusion Criteria:

- Current treatment with any other anti-neoplastic agent, including trastuzumab;
patients may continue to receive zoledronic acid for bone metastases or hypercalcemia

- Radiation therapy within 2 weeks of enrollment or surgery within 4 weeks

- Known brain or leptomeningeal metastatic disease requiring active therapy; (Patients
with asymptomatic previously treated metastases to these areas are eligible)

- Any of the following conditions within 6 months of enrollment: myocardial infarction,
severe/unstable angina, symptomatic congestive heart failure, cerebrovascular
accident or transient ischemic attack, coronary/peripheral artery bypass grafting;
patients who have experienced a pulmonary embolus, deep venous thrombosis or other
clinically significant thromboembolic event within 6 months of enrollment are
eligible if they are clinically stable on anticoagulation therapy

- Current active infection, including known human immunodeficiency virus (HIV)
positivity; for HIV patients on highly active antiretroviral therapy (HAART), the
pharmacokinetics of the investigation agent may be seriously affected; when
appropriate, 17-AAG will be studied in patients with HIV on HAART

- Pregnancy or breastfeeding; because of the unknown effects on the developing
fetus/newborn, patients who are pregnant or become pregnant should be excluded from
protocol study; exclusion of breast feeding women would also be appropriate as it is
not known whether 17-AAG may be excreted in breast milk and what effect this may have
on a developing newborn; female patients must agree to use effective contraception
during the study period, be surgically sterile, or be post-menopausal; in addition,
male patients will be required to use effective contraception during the study period
or be surgically sterile; the definition of effective contraception will be based on
the judgment of the investigator

- Serious allergy to eggs (i.e. hypotension, dyspnea, anaphylaxis, edema)

- Treatment with any agents that interact with cytochrome P450 3A should be avoided and
used with caution, if necessary; when possible, patients should be switched to
alternative medications; patients requiring anticoagulation should not be treated
with Coumadin and should be switched to a low molecular weight heparin injection;
patients receiving treatment with a low molecular weight heparin will require
episodic monitoring with the anti-factor Xa heparin assay

- Previous (within 5 years of enrollment) or current malignancies at other sites,
except adequately treated basal cell or squamous cell skin cancers and carcinoma in
situ of the cervix

- Other severe acute or chronic medical or psychiatric conditions or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration or may interfere with interpretation of study results and, in the
judgment of the investigator, would make the patient inappropriate for study entry

- The use of concomitant medications that prolong or may prolong QTc are excluded

- Patients who have significant cardiac disease including heart failure that meets New
York Heart Association (NYHA) class III and IV definitions, history of myocardial
infarction within one year of study entry, uncontrolled dysrhythmias, or poorly
controlled angina are excluded

- Patients who have a history of serious ventricular arrhythmia (VT or VF, >= 3 beats
in a row), QTc >= 450 msec for men and 470 msec for women, or LVEF =< 40% by MUGA are

- Patients with a prior history of cardiac or pulmonary toxicity after receiving
anthracyclines such as doxorubicin, daunorubicin, mitoxantrone, bleomycin or BCNU

- Patients with greater or equal to grade 2 pulmonary or cardiac symptoms prior to
study entry

- Patients with a history of prior radiation that potentially included the heart in the
field (e.g., mantle)

- Patients with active ischemic heart disease within 12 months

- Patients with a history of uncontrolled dysrhythmias or requiring antiarrhythmic

- Patients with congenital long QT syndrome; and patients with left bundle branch block

- Patients with symptomatic pulmonary disease requiring medication including the
following: dyspnea, dyspnea on exertion, paroxysmal nocturnal dyspnea, oxygen
requirement and significant pulmonary disease, including chronic
obstructive/restrictive pulmonary disease

- Patients that meet the Medicare criteria for home oxygen

- Patients with a prior history of chest radiation

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate (CR+PR)

Outcome Time Frame:

Up to 7 years

Safety Issue:


Principal Investigator

Elaina Gartner

Investigator Role:

Principal Investigator

Investigator Affiliation:

Wayne State University


United States: Food and Drug Administration

Study ID:




Start Date:

September 2005

Completion Date:

Related Keywords:

  • Recurrent Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Stage IV Breast Cancer
  • Breast Neoplasms



Wayne State University Detroit, Michigan  48202