Phase I Study of 17- Allylamino-17 Demethoxygeldanamycin (17-AAG) in Combination With Paclitaxel in Advanced Solid Malignancies

Study start date: May 1, 2004

Inclusion Criteria: Histologically confirmed solid malignancy Metastatic or unresectable disease Not amenable to standard curative or palliative therapy No known brain metastases Performance status - ECOG 0-2 More than 12 weeks Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 WBC ≥ 3,000/mm^3 AST and ALT ≤ 2.5 times upper limit of normal Bilirubin normal Creatinine normal Creatinine clearance ≥ 60 mL/min QTc < 450 msec for male patients (470 msec for female patients) LVEF > 40% by MUGA No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row) No myocardial infarction within the past year No New York Heart Association class III or IV congestive heart failure No poorly controlled angina No history of uncontrolled dysrhythmia or requirement for antiarrhythmic drugs No history of congenital long QT syndrome No active ischemic heart disease within the past year No left bundle branch block No other significant cardiac disease Not pregnant or nursing Negative pregnancy test Fertile patients must use effective double barrier contraception for at least 1 week before, during, and for at least 2 weeks after study participation No prior allergy to eggs No prior allergic reaction to compounds of similar chemical or biologic composition to 17-AAG or paclitaxel No peripheral neuropathy > grade 1 No concurrent uncontrolled illness No active or ongoing infection No psychiatric illness or social situation that would preclude study compliance No concurrent granulocyte colony-stimulating factors Prior paclitaxel allowed More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered No prior 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) More than 4 weeks since prior radiotherapy No prior radiotherapy that included the heart in the field (e.g., mantle radiotherapy) No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent therapeutic-dose warfarin for anticoagulation No concurrent medications that may prolong QTc interval No other concurrent investigational agents No other concurrent anticancer agents or therapies