Phase II Study of the Fully Human Monoclonal Antibody Against Transforming Growth Factor-beta (TGFβ) Receptor ALK1 (PF-03446962) in Relapsed or Refractory Urothelial Cancer (UC) Failing First-line Treatment.
This is an open-label, single arm, non randomised, phase II proof-of-concept study of the
monoclonal antibody against TGF-beta receptor ALK1 (PF03446962) for patients with urothelial
cancer relapsing/progressing after first line chemotherapy.
The study is planned according to Simon's Optimal two-stage design. The primary endpoint is
the proportion of patients who are progression-free at 2-months. A 2-month PFS rate of 50%
is not promising, while a 70% rate will be promising. In stage 1, 21 evaluable patients will
be accrued. If 12 patients at least will be progression-free at 2 months, enrollment will be
extended to the 2nd stage for further 24 patients. If, out of the total of 45 patients, 27
at least will be progression-free at 2 months, treatment will be declared worthy for further
Maximum overall accrual is 45 patients. Type I and type II error rates will be set both at
the 10% level.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression-free survival (PFS) is defined as the interval from the first dose of study drug to the date of the first documented disease progression or death for any reason, with censoring at the date of last contact for alive patients. A patient who has not progressed or died by the date of the analysis cut-off or when the patient received any further anticancer therapy would have the PFS censored at the time of last adequate tumor assessment before either cut-off date or the commencement of further anticancer therapy date, respectively.
Andrea Necchi, MD
Fondazione IRCCS Istituto Nazionale dei Tumori
Italy: The Italian Medicines Agency