Phase I Trial of Ganetespib, Capecitabine, and Radiation in Rectal Cancer

Exclusion Criteria

• •History of previous radiation therapy to the abdomen or pelvis
• •History of previous chemotherapy for rectal cancer
• •Major surgery within 4 weeks prior to first dose of ganetespib
• •Poor venous access for study drug administration. The study drug must be administered via peripheral venous access or through vascular access devices (VADs) (such as ports and peripherally-inserted central catheters \[PICCS\] containing silicone catheters. Use of VADs with catheters made of any other material is not allowed.
• •History of severe allergic or hypersensitivity reactions to excipients (e.g., Polyethylene glycol \[PEG\] 300 and Polysorbate 80)
• •Baseline corrected QT interval (QTc) \> 450 msec or previous history of QT prolongation while taking other medications
• •Ventricular ejection fraction (Ef) ≤ 55% at baseline
• •Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation)
• •Women who are pregnant or lactating
• •Uncontrolled intercurrent illness
• •Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study
• •Patients must be able to take oral medications.
• •Unequivocal metastatic disease on computed tomography or chest X-ray
• •Clinically significant comorbid conditions such as cardiovascular disease or significant peripheral vascular (e.g., uncontrolled hypertension, myocardial infarction, unstable angina) within 6 months of study entry, serious cardiac arrhythmia requiring medication, and uncontrolled infection.
• •Clinical evidence of bleeding diathesis or coagulopathy
• •Significant involvement of the bladder by the tumor