BL12: A Multicentre Randomized Phase II Trial Comparing Nab-Paclitaxel to Paclitaxel in Patients With Advanced Urothelial Cancer Progressing on or After a Platinum Containing Regimen

Inclusion Criteria27

• Histologically or cytologically confirmed diagnosis of TCC of the urinary tract (bladder, urethra, ureter, renal pelvis) and metastatic or locally advanced inoperable disease extent (T4, N2, N3 or M1 disease)
• Note: Mixed histologies (except small cell) permitted if predominately TCC by IHC.
• Patients must have evidence of metastatic disease, but measurable disease is not mandatory. To be considered evaluable for the overall response rate (complete and partial response), patients must have at least one measurable lesion as follows:
• X-ray, physical exam greater than or equal to 20 mm
• Conventional CT scan, MRI greater than or equal to 20 mm
• Spiral CT scan greater than or equal to 10 mm
• Male or female, 18 years of age or older.
• ECOG performance status less than or equal to 2 at study entry
• Adequate hematological, renal and hepatic functions as defined by the following required laboratory values obtained within 14 days prior to randomization. If anemic, patients should be asymptomatic and should not be decompensated.
• Absolute neutrophil count (ANC) greater than or equal to 1.5 x10^9/L (1,500 cells/mm3)
• Platelet count greater than or equal to 90 x10^9/L (100,000/mm3)
• Hemoglobin greater than or equal to 90 g/L
• Calculated creatinine clearance greater than 25 mL/min (Cockcroft and Gault formula)
• Total bilirubin less than or equal to 1.5 times the upper limit of normal (less than or equal to 2.5X if Gilbert's disease)
• ALT (SGPT) less than or equal to 3 x ULN or less than or equal to 5 x ULN if hepatic metastases are present
• Patients may have had prior neoadjuvant or adjuvant therapy for completely resected disease, provided it was completed at least 12 months prior to randomization. Patients must have recovered from any acute toxic effects to less than or equal to Grade 2 from any prior treatments. Neoadjuvant or adjuvant chemotherapy will be considered to have been first line therapy in the metastatic setting if the patient progressed within 12 months of the last dose.
• Patients must have received one and only one prior chemotherapeutic regimen which included a platinum (at least one cycle) for metastatic/recurrent disease. Treatment must have been discontinued at least 4 weeks prior to randomization in this study. Patients must have recovered from any acute toxic effects to less than or equal to Grade 2 from any prior treatments
• Patients may not have had any prior therapy with a taxane in any setting.
• Patients may have had prior investigational agents but these must have been discontinued at least 4 weeks prior to randomization. Patients must have recovered from any acute toxic effects less than or equal to Grade 2 from any prior treatments.
• Prior treatments with radiation therapy in the adjuvant and/or metastatic setting are permitted provided that at least 2 weeks have elapsed since the last fraction of radiation therapy and all treatment related adverse events are less than or equal to Grade 1 at the time of randomization.
• Patients may have had prior surgery provided that at least 4 weeks elapsed between the end of surgery and randomization onto the study. Patients must have recovered from any acute toxic effects less than or equal to Grade 2 from any prior treatments.
• Patients may have peripheral neuropathy from previous treatments assuming it is less than or equal to Grade 2.
• Patient is able (i.e. sufficiently fluent) and willing to complete the health and demographic, quality of life, and health utilities questionnaires in either English or French. The baseline assessment must be completed within required timelines, prior to registration/randomization. Inability (illiteracy in English or French, loss of sight, or other equivalent reason) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible.
• Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days prior to randomization. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, bilateral tubal ligation or vasectomy/vasectomized partner. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures.
• Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 1.5 hour's driving distance) placed on patients being considered for this trial. Investigators must assure themselves the patients registered on this trial will be available for complete documentation of the treatment, adverse events, response assessment and follow-up.
• In accordance with NCIC CTG policy, protocol treatment is to begin within 5 working days of patient randomization.