Trial aimed at evaluating the activity of the anti-ALK1 monoclonal antibody PF-03446962 in relapsed or refractory urothelial cancer (UC) failing first-line treatment.

Conditions: Relapsed or refractory urothelial cancer after failure of 1st line platinum-containing chemotherapy regimen for metastatic disease.
MedDRA version: 14.1Level: HLTClassification code 10038502Term: Renal pelvis and ureter neoplasms malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: PTClassification code 10044410Term: Transitional cell cancer of the renal pelvis and ureter recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: PTClassification code 10044412Term: Transitional cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: PTClassification code 10066750Term: Bladder transitional cell carcinoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2011-005983-12-IT

Lead Sponsor: ISTITUTO NAZIONALE PER LA CURA TUMORI

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

• Age > 18 years. • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. • Life expectancy of at least 12 weeks. • Histologically confirmed diagnosis of transitional cell tumors of the bladder or the urothelium. Presence of divergent histologies (ex. Squamous-cell histology) may be acceptable provided that there is prevalence of urothelial component. • Locally advanced/Metastatic disease. • Measurable disease criteria, defined as = 1 unidimensionally measurable lesion = 2 cm by conventional techniques or = 1 cm by spiral CT scan. • Failure of no more than 1 cisplatin-based conventional chemotherapy regimen for metastatic disease (pure second-line setting). • Neoadjuvant/adjuvant therapy considered if relapse occurred within 6 months of the last cycle of chemotherapy.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

• Treatment with any of the following anti-cancer therapies: o radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of PF-03446962 OR o chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of PF-03446962. • cardiovascular conditions within the past 6 months. • History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the activity of the drug in patients with relapsed/refractory transitional cell tumors receiving the following treatment program: IV doses of PF-03446962 monotherapy fortnightly until disease progression or onset of unacceptable toxicity.;Secondary Objective: To evaluate the safety and tolerability of PF-03446962 monotherapy in a population of chemotherapy pretreated patients with UC.;Primary end point(s): 2-month progression-free survival rate;Timepoint(s) of evaluation of this end point: 2-month

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Assessment of the safety and tolerability: incidence, nature and severity of treatment-related adverse events (AEs) will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03. • Assessment of response-rate by RECIST v1.1 criteria. RR (%) = CR + PR. • Response-rate according to densitometry (CT). • Overall Survival. • 2-month PFS in the per protocol population. • Correlation of PET response with CT response (RECIST and densitometry) and with PFS. • Quality of life changes according to ESAS score. • Correlative endpoints.;Timepoint(s) of evaluation of this end point: variable