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

NCT ID: NCT00004065

Last Updated: 2013-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-07-31
• Study Completion Date: 2005-03-31

Brief 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.

Detailed 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.

Conditions

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

Study Design

• Primary Study Purpose: TREATMENT

Interventions

tanespimycin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Principal Investigators

Howard I. Scher, MD

Role: STUDY_CHAIR

Memorial Sloan Kettering Cancer Center

Locations

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

CDR0000067267

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-T99-0035

Identifier Type: -

Identifier Source: secondary_id

UCLA-0206019

Identifier Type: -

Identifier Source: secondary_id

99-037

Identifier Type: -

Identifier Source: org_study_id