| | Requirement |
| 1 | Histologically confirmed transitional cell cancer (TCC/urothelial ca). Mixed histologies allowed as long as predominant histology is TCC.
|
| 2 | Must have received chemotherapy for TCC & have stage
IV TCC at study entry (appendix H). 1-3 prior systemic chemotherapeutic or investigational tx regimens for TCC are allowed.
|
| 3 | Specifically, must meet 1 or more of the following criteria:
Progressive Disease after treatment with a regimen that includes a platinum salt (e.g. carboplatin or cisplatin) for Stage IV disease.
OR Disease recurrence within 2 yrs (from date of last dose of chemotherapy or surgery until day consent is signed) after neoadjuvant or adjuvant therapy with a regimen that includes a platinum salt.
|
| 4 | Measurable or evaluable disease by RECIST. If all sites of measurable or evaluable disease have been irradiated, 1 site must have demonstrated growth after irradiation.
|
| 5 | Adequate contraception if of reproductive potential. WOCBP must have (-) serum pregnancy test within 7 days of study entry.
|
| 6 | ECOG 0- 1. |
| 7 | 18 y/o and above. |
| 8 | ANC 1500 or greater; Platelets 100,000 or greater. |
| 9 | Serum bilirubin 1.0, or less, x ULN |
| 10 | Creatinine Clearance 30 mL/min or greater (by Cockcroft-Gault formula). |
| 11 | Potassium 4.0 or greater. Ineligible if despite supplementation: K is < 4.0 or serum calcium (ionized or adjusted for albumin) & Mg out of normal range.
|
| 12 | In determining eligibility, the more abnormal of AST or ALT must be used. |
| 13 | The following describes hepatic eligibility:
Eligible if: Alk Phos is less than or equal to ULN & AST or ALT is less than or equal to ULN; Alk Phos is >1x but less than or equal to 2.5x ULN & AST or ALT is less than or equal to ULN; Alk Phos is > 2.5x but less than or equal to 5x ULN & AST or ALT is less than or equal to ULN; Alk Phos is less than or equal to ULN & AST or ALT is >1x but less than or equal to 1.5 x ULN; Alk Phos is > 1x but less than or equal to 2.5x ULN & AST or ALT is >1x but less than or equal to 1.5 x ULN; Alk Phos is less than or equal to ULN & AST or ALT is >1.5x but less than or equal to 5x ULN. |
| 14 | Signed Informed Consent (including HIPAA authorization). |
| 1 | Prior treatment of TCC with a taxane (e.g. docetaxel or paclitaxel) in any setting – neoadjuvant, adjuvant or metastatic. |
| 2 | Prior therapy with a VEGF-axis active agent, including antibodies to VEGF or VEGF receptors, or VEGF receptor tyrosine kinase inhibitors. |
| 3 | Severe or uncontrolled systemic disease or any concurrent condition which would make study participation undesirable to patient or would jeopardize protocol compliance. |
| 4 | Significant cardiac event such as heart attack or > 2 NYHA classification of heart disease ( Appendix D) within 3 mos before entry, or heart disease that increases risk of ventricular arrhythmia. |
| 5 | History of arrhythmia (multifocal PVCs, bigeminy, trigeminy, v-tach, or uncontrolled atrial fib) which is symptomatic or requires treatment (Gr 3) or asymptomatic sustained v-tach. (Medically controlled atrial fib is eligible). |
| 6 | History of QTc prolongation from medication that required discontinuation of that medication. |
| 7 | Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 y/o. |
| 8 | Left bundle branch block (LBBB). |
| 9 | QTc with Bazett’s correction (appendix G) that is unmeasurable, or 480 msec or greater on screening EKG. If QTc 480 msec or greater on screening EKG, EKG may be repeated 2x, at least 24 hrs apart; the average QTc from the 3 screening EKGs must be < 480 msec to be eligible.
|
| 10 | Any conmed that may cause QTc prolongation, induce Torsades de Pointes (Appendix C) or induce CYP3A4 function (Appendix E). |
| 11 | Hypertension not controlled by medical therapy. |
| 12 | Currently active diarrhea. |
| 13 | Pregnant or breast feeding women. |
| 14 | Any investigational agent, chemotherapy or radiotherapy within 28 days prior to D1. |
| 15 | Any unresolved > Gr 1 non-hematologic toxicity from prior anti-cancer therapy except alopecia. |
| 16 | Major surgery within 4 wks, or incompletely healed surgical incision prior to treatment. |
| 17 | Gr 2, or greater, peripheral neuropathy. |
| 18 | Previous or current malignancy within last 5 yrs, except cervical carcinoma in situ, adequately treated skin cancer, & adequately treated localized prostate cancer. |
| 19 | History of severe hypersensitivity reaction to drugs formulated with polysorbate 80. |
