Phase I Study of 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in Patients With an Advanced Solid Tumor or Lymphoma
17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in Treating Patients With an Advanced Solid Tumor or Lymphoma
Basic Trial Information
|Phase I||Treatment||Completed||18 and over||NCI||NCI-04-C-0218|
04-C-0218, 6544, NCI-6544, NCT00088868
Special Category: NCI Web site featured trial
- Determine the maximum tolerated dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in patients with an advanced malignant solid tumor or lymphoma.
- Determine the dose-limiting toxic effects and toxicity profile of this drug in these patients.
- Compare the effects of this drug on heat shock protein 90 (Hsp90) client proteins when assayed in peripheral blood mononuclear cells (PBMC) vs tumor tissue from patients treated with this drug.
- Correlate disturbances in key signaling pathways with administration of this drug in these patients.
- Determine the dose that alters key proteins in the majority of patients treated with this drug.
- Correlate serum proteomic patterns with target interactions or DMAG clinical effects in patients treated with this drug.
- Determine the pharmacokinetics of this drug in these patients.
- Histologically confirmed malignant solid tumor OR lymphoma
- Metastatic or unresectable disease
- Standard curative or palliative measures are not available OR are associated with minimal survival benefit
- No known brain metastases
- Treated brain metastases allowed provided they have been stable ≥ 6 months without steroids or anti-seizure medications
- More than 4 weeks since prior biologic therapy and recovered
- No concurrent prophylactic growth factors
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin, 8 weeks for UCN-01) and recovered
- See Disease Characteristics
- Concurrent hormonal therapy for prostate cancer allowed provided patient has metastatic disease that has progressed despite prior hormonal therapy
- More than 4 weeks since prior radiotherapy and recovered
- No prior radiotherapy that included the heart in the field (e.g., mantle radiotherapy)
- At least 4 weeks since prior major surgery
- At least 2 weeks since prior participation in a phase 0 study
- Concurrent bisphosphonates for any cancer allowed
- Concurrent preventative doses of aspirin or non-steroidal anti-inflammatory drugs allowed
- No concurrent drugs that may prolong QTc interval
- No concurrent full anticoagulation on a regular basis
- No concurrent prophylactic antiemetics
- No other concurrent investigational agents or therapies
- No other concurrent anticancer agents or therapies
- 18 and over
- More than 3 months
- Absolute neutrophil count ≥ 1,500/mm3
- Platelet count ≥ 100,000/mm3
- WBC ≥ 3,000/mm3
- Hemoglobin > 8 g/dL
- AST and ALT ≤ 2 times upper limit of normal
- Bilirubin ≤ 1.5 times normal
- PT and PTT ≤ 1.5 times normal (unless due to the presence of lupus anticoagulant or stable anticoagulation)
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No orthostatic hypotension > grade 2 (requiring more than brief fluid replacement or other therapy OR with physiological consequences)
- No New York Heart Association class III or IV heart failure
- LVEF ≥ 40% by MUGA
- QTc ≤ 450 msec (470 msec for women)
- No congenital long QT syndrome
- No myocardial infarction within the past year
- No active ischemic heart disease within the past year
- No history of uncontrolled dysrhythmias
- No history of serious ventricular arrhythmia (ventricular fibrillation or ventricular tachycardia > 3 premature ventricular contractions in a row)
- Not requiring antiarrhythmic drugs
- No poorly controlled angina
- No left bundle branch block
- No uncontrolled symptomatic pulmonary disease, including any of the following:
- Dyspnea off or on exertion
- Paroxysmal nocturnal dyspnea
- Severe chronic obstructive/restrictive pulmonary disease requiring daily chronic medications and oxygen
- Must not meet the Medicare criteria for home oxygen
- No sufficiently compromised pulmonary status as measured by baseline pulmonary function tests and DLCO
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 2 months after study participation
- No known HIV positivity
- No hyponatremia indicated by sodium < 130 mmol/L
- No known immunodeficiency syndromes
- No history of allergic reaction attributed to compounds of similar chemical or biological composition to 17-dimethylaminoethylamino-17-demethoxygeldanamycin (geldanamycin or 17-AAG)
- No concurrent uncontrolled illness
- No active or ongoing uncontrolled infection
- No psychiatric illness or social situation that would preclude study compliance
Approximately 40 patients will be accrued for this study within 2 years.
This is a single-center, dose-escalation study.
Patients receive 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) IV over 1-2 hour on days 1 and 4 or days 2 and 5 weekly for 4 weeks. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 1-6 patients receive escalating doses of 17-DMAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of up to 6 patients experience dose-limiting toxicity. Once the MTD is determined, 10 additional patients are treated at the MTD.
Trial Contact Information
Trial Lead Organizations
NCI - Center for Cancer Research
|Official Title||A Phase I Study Of 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17DMAG) With Evaluation Of Hsp90 Client Proteins In Subjects With Solid Tumors And Lymphomas|
|Trial Start Date||2004-06-24|
|Trial Completion Date||2010-03-24|
|Registered in ClinicalTrials.gov||NCT00088868|
|Date Submitted to PDQ||2004-06-16|
|Information Last Verified||2007-05-13|
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.