Clinical trial · Interventional

PF-03446962 in Relapsed or Refractory Urothelial Cancer

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.

NCT01620970CI-TRIAL-00051819completedPhase 2ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

Salvage chemotherapy for advanced urothelial cancer (UC) yields suboptimal response rates of 15-40%, a median progression-free survival of 2-4 months and a median overall survival of 6 months. A rationale for targeting angiogenesis in UC is supported by preclinical evidences and early signals of clinical activity of anti-VEGF TKI as demonstrated by our group with the use of pazopanib. Despite this activity, progression inevitably occurs and mechanisms determining resistance to conventional anti-angiogenic agents are under investigation. PF-03446962 (Pfizer Inc) is a novel fully human monoclonal antibody (mAb) against ALK1 with dose-dependent antiangiogenic activity as demonstrated in nonclinical studies in a chimera mouse model bearing human tumor xenograft. The investigators suggest that PF-03446962 may increase current results for patients with advanced urothelial cancer failing upfront chemotherapy due to its mechanisms of action. Due to the lack of reliable and reproducible predictors of response as well as of imaging tools to assess tumor response, the trial will provide incorporation of 18FDG-PET/CT and contrast-enhanced ultrasound to stage and evaluate response of urothelial cancers, together with standard imaging modalities (RECIST criteria). Blood and tissue samples will be collected for translational purposes.

Conditions

Conditions (1)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Transitional Cell Carcinoma of Bladder	—	UNRESOLVED	—

Interventions

Interventions (1)

Intervention	Type	Mapped drug	Match
PF03446962	Drug	—	UNRESOLVED

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
PF03446962
description
Investigational study drug, administered intravenously every 2 weeks until disease progression or unacceptable toxicity.
interventionNames
1. Drug: PF03446962

Primary outcomes (1)

measure
Progression-free survival.
timeFrame
2-month
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.

Secondary outcomes (4)

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years

Show eligibility criteria text

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.

References

Publications (2)

BACKGROUNDHu-Lowe DD, Chen E, Zhang L, Watson KD, Mancuso P, Lappin P, Wickman G, Chen JH, Wang J, Jiang X, Amundson K, Simon R, Erbersdobler A, Bergqvist S, Feng Z, Swanson TA, Simmons BH, Lippincott J, Casperson GF, Levin WJ, Stampino CG, Shalinsky DR, Ferrara KW, Fiedler W, Bertolini F. Targeting activin receptor-like kinase 1 inhibits angiogenesis and tumorigenesis through a mechanism of action complementary to anti-VEGF therapies. Cancer Res. 2011 Feb 15;71(4):1362-73. doi: 10.1158/0008-5472.CAN-10-1451. Epub 2011 Jan 6. PMID 21212415
DERIVEDNecchi A, Giannatempo P, Mariani L, Fare E, Raggi D, Pennati M, Zaffaroni N, Crippa F, Marchiano A, Nicolai N, Maffezzini M, Togliardi E, Daidone MG, Gianni AM, Salvioni R, De Braud F. PF-03446962, a fully-human monoclonal antibody against transforming growth-factor beta (TGFbeta) receptor ALK1, in pre-treated patients with urothelial cancer: an open label, single-group, phase 2 trial. Invest New Drugs. 2014 Jun;32(3):555-60. doi: 10.1007/s10637-014-0074-9. Epub 2014 Feb 26. PMID 24566706

Registry

Dates and enrollment

Start: Mar 1, 2012
Primary completion: Jun 1, 2013
Completion: Jun 1, 2013
First posted: Jun 15, 2012
Last update posted: May 14, 2021
Enrollment: 14 (actual)
Lead sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano OTHER
Keywords: 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

Data updated 22 days agoSource updated May 14, 2021source: clinicaltrials

Locations

Locations by country (1)

Country	Sites	Recruiting
Italy	1	0

Trial listing is informational. Eligibility is decided by the study team; contact information is on ClinicalTrials.gov.