PF-03446962 in Relapsed or Refractory Urothelial Cancer

NCT01620970 | Completed Phase 2 DMC

• 2 other identifiers: INT01/122011-005983-12
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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

Transitional Cell Carcinoma of Bladder

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

Outcome Measures

Primary Outcomes (1)

• Progression-free survival.

  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.

  2-month

Secondary Outcomes (4)

• Safety (CTCAE v.4.03)

  2-month

• RECIST response-rate

  2-month

• Overall Survival

  6-month

• Circulating and Tissue Biomarkers

  Baseline and 2 months

Study Arms (1)

PF03446962

EXPERIMENTAL

Investigational study drug, administered intravenously every 2 weeks until disease progression or unacceptable toxicity.

Drug: PF03446962

Interventions

PF03446962 DRUG

PF-03446962 will be administered in 1hr intravenously at a dose of 10 mg/Kg on day 1, then every 2 weeks until the evidence of disease progression or onset of unacceptable toxicity.

PF03446962

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Related Publications (2)

• Hu-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 BACKGROUND

• Necchi 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 DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Neoplasm Metastasis; Urinary Bladder Neoplasms; Recurrence; Camurati-Engelmann Syndrome

Interventions

ascrinvacumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Disease Attributes; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Andrea Necchi, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  PRINCIPAL INVESTIGATOR

• Filippo G De Braud, MD

  filippo.debraud@istitutotumori.mi.it

  STUDY CHAIR

• Alessandro M Gianni, MD

  University of Milan and Fondazione IRCCS Istituto Nazionale dei Tumori

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 11, 2012
• First Posted: June 15, 2012
• Study Start: March 1, 2012
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: May 14, 2021

Record last verified: 2021-05

Locations

IT (1)