Phase I Study of IPI-504 and Docetaxel in Patients With Advanced Solid Tumors

Exclusion Criteria

• •Treatment within 1 week of the start of IPI-504 for erlotinib, and imatinib; within 2 weeks for gefitinib, and any other tyrosine kinase inhibitor (approved or investigational); within 4 weeks for any biologic therapy (antibody, vaccine, or other protein-based therapy), radiation therapy, or conventional chemotherapy; within 6 weeks for nitrosoureas or mitomycin C.
• •Radiation therapy within 2 weeks of the start of IPI-504. (Patients must have recovered from any toxicities.)
• •Concurrent radiation therapy or treatment with any other investigational agent is not permitted.
• •Use of a medication or food that is a clinically relevant CYP3A inhibitor or inducer within 2 weeks prior to Cycle 1, Dose 1.
• •Symptomatic peripheral neuropathy ≥ Grade 2.
• •Inadequate hematologic function defined by absolute neutrophil count (ANC) \<1,500 cells/mm3, a platelet count \<100,000/mm3, and a hemoglobin \<9.0 g/dL (may be increased to this level with transfusion as long as there is no evidence of active bleeding).
• •Inadequate renal function defined by AST and/or ALT \>1.5; total bilirubin above the upper limit of normal.
• •Inadequate renal function defined by serum creatinine \>1.5 x ULN.
• •Sinus bradycardia (resting heart rate \<50) secondary to intrinsic conduction system disease. Patients with sinus bradycardia secondary to pharmacologic treatment may enroll if withdrawal of the treatment results in normalization of the resting heart rate to within normal limits.
• •Baseline QTc \>450 msec in males; QTc \>470 msec in females, or previous history of QT prolongation while taking other medications.
• •Presence of left bundle branch block, right bundle branch block plus left anterior hemiblock, bifasicular block or 3rd degree heart block. This does not include patients with a history of these events with adequate control by pacemaker.
• •Patients who have received \>450 mg/m2 of any anthracycline during prior chemotherapy must have a baseline LVEF \>40%.
• •Active keratitis or keratoconjunctivitis.
• •History of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80.
• •Presence of active infection or systemic use of antibiotics within 72 hours of treatment.
• •Untreated brain metastases. Note: Patients with a history of brain metastases are eligible as long as definitive treatment has been given and patients are clinically stable.
• •Significant co-morbid condition or disease which in the judgment of the Investigator would place the patient at undue risk or interfere with the study (e.g., cardiac disease such as acute coronary syndrome or unstable angina within 6 months, uncontrolled hypertension, arrhythmia requiring medication or mechanical control, cirrhotic liver disease, or other conditions).
• •Previous or current malignancies at other sites within the last 2 years, with exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin.
• •HIV-positive patients receiving combination antiretroviral therapy.
• •Women who are pregnant or lactating.
• •Previous treatment with 17-AAG, DMAG, or other known Hsp90 inhibitor.
• •Patients with prior hepatic resection or hepatic-directed therapy (e.g., chemoembolization or Theresphere).
• •Prior treatment with docetaxel
• •Three or more chemotherapy regimens for metastatic disease. Note: Any number of prior treatment regimens with tyrosine kinase inhibitors is permitted.