Tanespimycin in Treating Women With Refractory Locally Advanced or Metastatic Breast Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT00096109
• Collaborator: (none)
• Enrollment: 11
• Location: 1
• Arm: 1
• Duration (Months): 80
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase II trial is studying how well tanespimycin works in treating women with refractory locally advanced or metastatic breast cancer. Drugs used in chemotherapy, such as tanespimycin, work in different ways to stop tumor cells from dividing so they stop growing or die

Condition or Disease	Intervention/Treatment	Phase
Recurrent Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer	Drug: tanespimycin; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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

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

3. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Clinical Trial of 17-Allyamino-17-Demethoxygeldanamycin (17-AAG) in Chemotherapy Refractory Metastatic Breast Cancer
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (tanespimycin) 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.	Drug: tanespimycin; Given IV; Other Names: 17-AAG ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Response Rate (Complete Response (CR) +Partial Response (PR) [Up to 7 years]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

2. Progression Free Survival (PFS) [Up to 7 years]

   PFS is defined as either progression or death, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

3. Her2/Neu Status [Baseline]

   Response rates will be estimated separately for her2/neu positive and her2/neu negative individuals along with 95% confidence intervals. PLEASE NOTE: IT WAS PROPOSED TO ANALYZE OUTCOME BY HER2 STATUS, NO DATA WAS COLLECTED OR EVALUATED.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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 excluded

• 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 drugs

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48202

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Elaina Gartner, Wayne State University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00096109
• Other Study ID Numbers: NCI-2012-03058; C-2803; U01CA062502; U01CA062487; CDR0000391198
• First Posted: Nov 9, 2004
• Last Update Posted: Jan 16, 2017
• Last Verified: Nov 1, 2016

• Additional relevant MeSH terms: Breast Neoplasms

Study Results

Participant Flow

Recruitment Details	Cancer center clinic.

Arm/Group Title	Treatment (Tanespimycin)
Arm/Group Description	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. Laboratory biomarker analysis: Correlative studies (was not completed due to the small number of samples)
Period Title: Overall Study
STARTED	11
COMPLETED	11
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Tanespimycin)
Arm/Group Description	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.
Overall Participants	11
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 81.8%
>=65 years	2 18.2%
Gender (Count of Participants)
Female	11 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	11 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate (Complete Response (CR) +Partial Response (PR)
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	Up to 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Tanespimycin)
Arm/Group Description	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. Laboratory biomarker analysis: Correlative studies (was not completed due to the small number of samples)
Measure Participants	7
Count of Participants [Participants]	0 0%

2. Primary Outcome

Title	Progression Free Survival (PFS)
Description	PFS is defined as either progression or death, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	Up to 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Tanespimycin)
Arm/Group Description	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. Laboratory biomarker analysis: Correlative studies (was not completed due to the small number of samples)
Measure Participants	11
Median (95% Confidence Interval) [months]	2

3. Primary Outcome

Title	Her2/Neu Status
Description	Response rates will be estimated separately for her2/neu positive and her2/neu negative individuals along with 95% confidence intervals. PLEASE NOTE: IT WAS PROPOSED TO ANALYZE OUTCOME BY HER2 STATUS, NO DATA WAS COLLECTED OR EVALUATED.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

No participants were evaluated for her2/neu status.

Arm/Group Title	Treatment (Tanespimycin)
Arm/Group Description	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. Laboratory biomarker analysis: Correlative studies (was not completed due to the small number of samples)
Measure Participants	0

Adverse Events

Time Frame	30 days after the last dose of treatment
Arm/Group Title	Treatment (Tanespimycin)
Arm/Group Description	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. tanespimycin: Given IV laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Treatment (Tanespimycin)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Tanespimycin)
	Affected / at Risk (%)	# Events
Total	6/11 (54.5%)
Blood and lymphatic system disorders
Anemia	1/11 (9.1%)	1
Gastrointestinal disorders
Nausea	1/11 (9.1%)	1
General disorders
Fatigue	1/11 (9.1%)	1
Immune system disorders
Anaphylaxis	1/11 (9.1%)	1
Infections and infestations
Urinary Tract Infection	1/11 (9.1%)	1
Lung Infection	1/11 (9.1%)	1
Pleural Infection	1/11 (9.1%)	1
Investigations
Aspartate Aminotransferase Increased	1/11 (9.1%)	1
Alkaline Phosphatase Increased	1/11 (9.1%)	1
Alkaline Phosphatase Increased	2/11 (18.2%)	2
Blood Bilirubin Increased	1/11 (9.1%)	1
Metabolism and nutrition disorders
Dehydration	1/11 (9.1%)	1
Hyperglycemia	1/11 (9.1%)	1
Hypokalemia	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/11 (9.1%)	1
Dyspnea	1/11 (9.1%)	1
Voice Alteration	1/11 (9.1%)	1
Respiratory, Thoracic, and Mediastinal Disorders - Other, specify	2/11 (18.2%)	2
Vascular disorders
Hypotension	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Tanespimycin)
	Affected / at Risk (%)	# Events
Total	9/11 (81.8%)
Blood and lymphatic system disorders
Anemia	7/11 (63.6%)	11
Cardiac disorders
Sinus Tachycardia	1/11 (9.1%)	1
Ventricular Arrhythmia	1/11 (9.1%)	1
Eye disorders
Blurred Vision	1/11 (9.1%)	2
Gastrointestinal disorders
Vomiting	1/11 (9.1%)	1
Diarrhea	3/11 (27.3%)	5
Constipation	2/11 (18.2%)	2
Nausea	3/11 (27.3%)	4
Abdominal Pain	1/11 (9.1%)	1
General disorders
Edema Limbs	1/11 (9.1%)	1
Fatigue	3/11 (27.3%)	4
Hepatobiliary disorders
Hepatobiliary Disorders - Other	1/11 (9.1%)	2
Infections and infestations
Infections and Infestations - Other	1/11 (9.1%)	2
Investigations
Lymphocyte Count Decreased	3/11 (27.3%)	3
Blood Bilirubin Increased	2/11 (18.2%)	2
Alanine Aminotransferase Increased	3/11 (27.3%)	4
Aspartate Aminotransferase	5/11 (45.5%)	7
White Blood Cell Decreased	2/11 (18.2%)	3
Alkaline Phosphatase Increased	3/11 (27.3%)	5
Metabolism and nutrition disorders
Anorexia	4/11 (36.4%)	6
Hyperglycemia	4/11 (36.4%)	7
Hypermagnesemia	2/11 (18.2%)	4
Hypocalcemia	2/11 (18.2%)	5
Hypercalcemia	2/11 (18.2%)	3
Hyponatremia	1/11 (9.1%)	1
Hypoalbuminemia	1/11 (9.1%)	2
Hypokalemia	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
Pain In Extremity	1/11 (9.1%)	1
Arthralgia	1/11 (9.1%)	1
Generalized Muscle Weakness	1/11 (9.1%)	1
Bone Pain	1/11 (9.1%)	3
Myalgia	1/11 (9.1%)	3
Nervous system disorders
Headache	2/11 (18.2%)	2
Peripheral Sensory Neuropathy	1/11 (9.1%)	1
Psychiatric disorders
Confusion	1/11 (9.1%)	1
Renal and urinary disorders
Urinary Tract Pain	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/11 (9.1%)	1
Cough	1/11 (9.1%)	1
Skin and subcutaneous tissue disorders
Body Odor	1/11 (9.1%)	1

Limitations/Caveats

Because of the frequency of toxicities experienced by the pts & lack of response, study closed to accrual before all 17 planned pts were enrolled. It was proposed to analyze outcome by HER2 status,but no HER2 data was collected.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.