Chemotherapy in Treating Patients With Refractory Advanced Solid Tumors or Hematologic Cancer

Breast Cancer Clinical Trial

Official title:

A Phase I Trial of 17-N-Allylamino-17-Demethoxy Geldanamycin (17-AAG, NSC #330507) Daily X 5 in Patients With Advanced Cancer Therapeutic Protocol

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004065
• Other study ID #: 99-037
• Secondary ID: CDR0000067267NCI
• Status: Completed
• Phase: Phase 1
• First received: December 10, 1999
• Last updated: June 20, 2013
• Start date: July 1999
• Est. completion date: March 2005

Study information

• Verified date: June 2013
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin in treating patients with refractory advanced solid tumors or hematologic cancers.

Description:

OBJECTIVES:

• Determine the maximum tolerated dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) in patients with refractory or advanced solid tumors or hematologic malignancies.

• Evaluate the effects of this drug on the expression of signaling proteins present on an individual patient's cancer at the start of treatment and, if possible, post treatment.

OUTLINE: This is a two-phase, dose-escalation, multicenter study. Patients are stratified according to disease (chronic myelogenous leukemia [CML] or Philadelphia chromosome [Ph]+ acute lymphoblastic leukemia [ALL] vs solid tumor).

Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 60-90 minutes twice weekly. Courses repeat every 12 weeks in the absence of disease progression (after at least 2 courses for CML or Ph+ ALL patients) or unacceptable toxicity.

• Accelerated phase: Single patients receive escalating dose levels of 17-AAG until one patient experiences a first course grade 3 or greater toxicity or two different patients experience grade 2 toxicity during any course.

• Standard phase: Cohorts of 3-6 patients in each stratum receive escalating doses of 17-AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 51 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: March 2005
• Est. primary completion date: March 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

• Histologically confirmed advanced primary or malignant solid tumor refractory to standard therapy or for which no curative standard therapy exists

• Progressive disease evidenced by 1 of the following:

• Non-prostate cancer (including, but not limited to, breast, ovary, head and neck, non-small cell lung, bladder, kidney, colon, stomach, or malignant melanoma)

• Development of new lesions or an increase in existing lesions

• No increase in a biochemical marker (e.g., carcinoembryonic antigen, CA-15-3, or an increase in symptoms) as sole measure of disease

• Prostate cancer (androgen independent) meeting the following criteria:

• Progressing metastatic disease on bone scan, CT scan, or MRI

• Metastatic disease and rising prostate-specific antigen (PSA) values meeting 1 of the following criteria:

• At least 3 rising PSA values obtained at least 1 week apart = 2 rising values more than 1 month apart with at least 25% increase over the range of values

• Serum testosterone less than 30 ng/mL

• Castrate status should be maintained by medical therapies if orchiectomy has not been performed

• Progressive disease must be evident off antiandrogen therapy if received prior to study entry

• Registered to protocol MSKCC-9040

• Cytologically confirmed chronic, accelerated, or blastic phase chronic myelogenous leukemia (CML) or Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) refractory to standard therapy or for which no curative therapy exists

• Progressive disease evidenced by 1 of the following:

• Accelerated or blastic phase disease that is not responsive to standard therapy or loss of hematologic response to imatinib mesylate while remaining in chronic phase for CML

• Relapsed or refractory after treatment with standard chemotherapy and imatinib mesylate for Ph-positive ALL

• No active CNS or epidural tumor

• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Not specified

Menopausal status:

• Not specified

Performance status:

• Karnofsky 70-100%

Life expectancy:

• At least 6 months

Hematopoietic:

• WBC greater than 3,500/mm^3

• Platelet count greater than 100,000/mm^3

• No restrictions based on peripheral blood counts for CML and Ph-positive ALL

Hepatic:

• Bilirubin no greater than 1.2 times upper limit of normal (ULN)

• AST less than 1.5 times ULN

• Prothrombin time normal

Renal:

• Creatinine no greater than 1.5 times ULN OR

• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• No myocardial infarction within the past 6 months

• Ejection fraction greater than 45% by radionuclide cardiac angiography

• No ventricular aneurysm or other abnormal wall motion

• No reversible defect by thallium stress test if any of the following conditions are present:

• Ejection fraction less than 45% on radionuclide angiocardiography

• Worrisome but nonexclusive cardiovascular history

• Abnormal echocardiogram

• Patients with the following history or clinical findings require additional diagnostic testing:

• Significant Q waves (greater than 3 mm or greater than one-third of the height of the QRS complex)

• ST elevation or depressions of greater than 2 mm that are not attributable to hypertension strain

• Absence of regular sinus rhythm

• Bundle branch block

• Requirement for diuretics for reasons other than hypertension or digoxin for reasons other than atrial fibrillation

• Prior mild to moderate congestive heart failure

• No New York Heart Association class III or IV heart disease

• No angina pectoris

• No uncontrolled hypertension or intermittent claudication

• No severe debilitating valvular disease

Pulmonary:

• No severe debilitating pulmonary disease

Other:

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No active infection requiring IV antibiotics

• No symptomatic peripheral neuropathy grade 2 or higher

• No other severe medical conditions that would increase risk for toxicity

• No allergy to eggs or egg products

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior biologic therapy (including interferon for CML) and recovered

Chemotherapy:

• At least 4 weeks since prior chemotherapy (3 days for hydroxyurea for CML or ALL) and recovered

• No other concurrent chemotherapy

Endocrine therapy:

• See Disease Characteristics

• At least 4 weeks since prior endocrine therapy and recovered

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered

• Concurrent radiotherapy to localized disease sites not being used to evaluate antitumor response allowed

• No concurrent radiotherapy to only measurable lesion

Surgery:

• See Disease Characteristics

• Prior orchiectomy allowed

• No concurrent surgery

Other:

• At least 3 days since prior imatinib mesylate for CML or ALL

• At least 4 weeks since prior investigational anticancer drugs and recovered

• At least 4 weeks since prior palliative treatment for metastatic disease

• No concurrent ketoconazole, warfarin, verapamil, miconazole, or erythromycin

• No other concurrent investigational drugs

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Cancer
• Breast Cancer
• Colorectal Cancer
• Gastric Cancer
• Head and Neck Cancer
• Head and Neck Neoplasms
• Kidney Cancer
• Leukemia
• Lung Cancer
• Melanoma (Skin)
• Ovarian Cancer
• Prostate Cancer
• Prostatic Neoplasms
• Stomach Neoplasms
• Unspecified Adult Solid Tumor, Protocol Specific
• Urinary Bladder Neoplasms

Intervention

Drug:
• tanespimycin

Locations

Country	Name	City	State
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,