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.
18 Years
N/A
Both
Transitional Cell Carcinoma of Bladder
Trial Information
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
investigations.
Maximum overall accrual is 45 patients. Type I and type II error rates will be set both at
the 10% level.
Inclusion Criteria:
- Age > 18 years.
- ECOG Performance status of 0 or 1.
- Life expectancy of at least 12 weeks.
- Measurable disease criteria (RECIST v1.1).
- Histological diagnosis of urothelial cancer.
- Locally advanced or metastatic disease.
- Failure of at least 1 prior chemotherapy regimen for metastatic disease.
- Neoadjuvant/adjuvant therapy considered if relapse occurred within 6 months of the
last cycle of chemotherapy.
- Adequate bone marrow, liver and renal function requirements, to be conducted within 7
days prior to screening.
Exclusion Criteria:
- Cardiovascular or CNS disease.
- Previously untreated CNS metastases.
- Active Hepatitis B, C, HIV infection.
- Pregnant or breast-feeding patients.
- GI abnormalities and any other clinical condition at high risk of bleeding.
- Substance abuse and any other condition which may interfere with patient's
participation in the study or evaluation of study results.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Progression-free survival.
Outcome Description:
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.
Outcome Time Frame:
2-month
Safety Issue:
No
Principal Investigator
Andrea Necchi, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Fondazione IRCCS Istituto Nazionale dei Tumori
Authority:
Italy: The Italian Medicines Agency
Study ID:
INT01/12
NCT ID:
NCT01620970
Start Date:
July 2012
Completion Date:
October 2013
Related Keywords:
- Transitional Cell Carcinoma of Bladder
- Transitional Cell Carcinoma
- Metastatic disease
- Bladder tumors, Recurrent
- Angiogenesis
- PF03446962
- Transforming growth factor beta
- Activin receptor like kinase 1
- Monoclonal Antibody
- Locally advanced or metastatic disease
- Failure of one platinum-based chemotherapy
- Measurable disease
- Urinary Bladder Neoplasms
- Carcinoma
- Carcinoma, Transitional Cell
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