Clofarabine Therapy in Locally Advanced or Metastatic Urothelial Carcinoma

Determining the maximum tolerated dose (MTD)

The objective of the dose selection phase is to determine the maximum tolerated dose (MTD) or confirm that the start dose level of clofarabine is safe. The MTD is defined as the highest dose at which the probability of toxicity remains below the target toxicity threshold. MTD estimation will be based on the observed dose-dependent incidence rate of dose-limiting toxicity (DLT) within the first 28 days of dosing (Cycle 1). Patients eligible for MTD evaluation include: * Those who completed Cycle 1 and took at least 80% of the required total dose of the study drug (protocol-defined dose reductions will not be considered noncompliance). * Those who discontinued during Cycle 1 due to a DLT.

Objective response rate (ORR)

Objective response rate (ORR) is defined as the percentage of patients whose best response is either a complete response (CR) or partial response (PR). Patients for whom best tumor response is not CR or PR, as well as patients without any efficacy assessment will be considered non-responders. According to RECIST v1.1, confirmation of PR and CR is not required considering the nature of the study and the protocol requirements.

Duration of response (DOR)

Duration of response (DOR) (for PR and CR) is defined as the time from the first documented objective response of PR or CR, whichever is noted earlier, to disease progression or death (if death occurs before progression is documented). DOR will be defined for responders only, i.e. patients with a CR or PR. The actual dates the tumor scans were performed will be used for this calculation. DOR for patients who have not progressed or died at the time of analysis will be censored at the date of their last tumor assessment.

Progression-free survival (PFS)

Progression-free survival (PFS) is defined as the time (days) from start of study treatment to date of first observed disease progression (investigator's radiological or clinical assessment) or death due to any cause, if death occurs before progression is documented. The actual date that the tumor scan was performed will be used for this calculation. If a tumor assessment is performed over more than one day (e.g. scans for chest and abdomen done on different days for the same evaluation), the earliest date will be used for the calculation of PFS. For patients without documented radiological or clinical progression or death at the time of analysis, PFS will be censored at the last actual visit date of tumor evaluation.

Overall survival (OS)

Overall survival (OS) is defined as the time from start of study treatment to death due to any cause. Patients alive at the date of data cut-off for analysis will be censored at the last date known to be alive. If a patient is lost to follow-up before any assessment after assignment to treatment, this patient will be censored at 1 day.