Chemotherapy in Treating Patients With Refractory Advanced Solid Tumors or Hematologic Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
OBJECTIVES:
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Determine the maximum tolerated dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) in patients with refractory or advanced solid tumors or hematologic malignancies.
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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.
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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.
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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.
Study Design
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
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Diagnosis of 1 of the following:
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Histologically confirmed advanced primary or malignant solid tumor refractory to standard therapy or for which no curative standard therapy exists
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Progressive disease evidenced by 1 of the following:
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Non-prostate cancer (including, but not limited to, breast, ovary, head and neck, non-small cell lung, bladder, kidney, colon, stomach, or malignant melanoma)
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Development of new lesions or an increase in existing lesions
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No increase in a biochemical marker (e.g., carcinoembryonic antigen, CA-15-3, or an increase in symptoms) as sole measure of disease
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Prostate cancer (androgen independent) meeting the following criteria:
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Progressing metastatic disease on bone scan, CT scan, or MRI
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Metastatic disease and rising prostate-specific antigen (PSA) values meeting 1 of the following criteria:
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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
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Serum testosterone less than 30 ng/mL
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Castrate status should be maintained by medical therapies if orchiectomy has not been performed
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Progressive disease must be evident off antiandrogen therapy if received prior to study entry
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Registered to protocol MSKCC-9040
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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
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Progressive disease evidenced by 1 of the following:
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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
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Relapsed or refractory after treatment with standard chemotherapy and imatinib mesylate for Ph-positive ALL
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No active CNS or epidural tumor
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Hormone receptor status:
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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:
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WBC greater than 3,500/mm^3
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Platelet count greater than 100,000/mm^3
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No restrictions based on peripheral blood counts for CML and Ph-positive ALL
Hepatic:
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Bilirubin no greater than 1.2 times upper limit of normal (ULN)
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AST less than 1.5 times ULN
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Prothrombin time normal
Renal:
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Creatinine no greater than 1.5 times ULN OR
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Creatinine clearance greater than 60 mL/min
Cardiovascular:
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No myocardial infarction within the past 6 months
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Ejection fraction greater than 45% by radionuclide cardiac angiography
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No ventricular aneurysm or other abnormal wall motion
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No reversible defect by thallium stress test if any of the following conditions are present:
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Ejection fraction less than 45% on radionuclide angiocardiography
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Worrisome but nonexclusive cardiovascular history
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Abnormal echocardiogram
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Patients with the following history or clinical findings require additional diagnostic testing:
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Significant Q waves (greater than 3 mm or greater than one-third of the height of the QRS complex)
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ST elevation or depressions of greater than 2 mm that are not attributable to hypertension strain
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Absence of regular sinus rhythm
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Bundle branch block
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Requirement for diuretics for reasons other than hypertension or digoxin for reasons other than atrial fibrillation
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Prior mild to moderate congestive heart failure
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No New York Heart Association class III or IV heart disease
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No angina pectoris
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No uncontrolled hypertension or intermittent claudication
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No severe debilitating valvular disease
Pulmonary:
- No severe debilitating pulmonary disease
Other:
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Not pregnant or nursing
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Negative pregnancy test
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Fertile patients must use effective contraception
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No active infection requiring IV antibiotics
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No symptomatic peripheral neuropathy grade 2 or higher
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No other severe medical conditions that would increase risk for toxicity
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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:
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At least 4 weeks since prior chemotherapy (3 days for hydroxyurea for CML or ALL) and recovered
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No other concurrent chemotherapy
Endocrine therapy:
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See Disease Characteristics
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At least 4 weeks since prior endocrine therapy and recovered
Radiotherapy:
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At least 4 weeks since prior radiotherapy and recovered
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Concurrent radiotherapy to localized disease sites not being used to evaluate antitumor response allowed
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No concurrent radiotherapy to only measurable lesion
Surgery:
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See Disease Characteristics
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Prior orchiectomy allowed
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No concurrent surgery
Other:
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At least 3 days since prior imatinib mesylate for CML or ALL
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At least 4 weeks since prior investigational anticancer drugs and recovered
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At least 4 weeks since prior palliative treatment for metastatic disease
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No concurrent ketoconazole, warfarin, verapamil, miconazole, or erythromycin
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No other concurrent investigational drugs
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Jonsson Comprehensive Cancer Center, UCLA | Los Angeles | California | United States | 90095 |
| 2 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10021 |
Sponsors and Collaborators
- Memorial Sloan Kettering Cancer Center
- National Cancer Institute (NCI)
Investigators
- Study Chair: Howard I. Scher, MD, Memorial Sloan Kettering Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 99-037
- CDR0000067267
- NCI-T99-0035
- UCLA-0206019