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
tanespimycin
Urogenital Diseases+99
+ Genital Diseases
+ Adenocarcinoma
Treatment Study
Summary
Study start date: July 1, 1999
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 2 locations
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, United StatesOpen Jonsson Comprehensive Cancer Center, UCLA in Google MapsMemorial Sloan-Kettering Cancer Center
New York, United States