Clinical Trial: Phase II Trial of the Gamma-Secretase Inhibitor PF-03084014 in Adults With Desmoid Tumors/Aggressive Fibromatosis
Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional
Official Title: Phase II Trial of the Gamma-Secretase Inhibitor PF-03084014 in Adults With Desmoid Tumors/Aggressive Fibromatosis
Brief Summary:
Background:
- Desmoid tumors (also known as aggressive fibromatosis), are rare, locally invasive, slow-growing soft-tissue tumors. The disease can be either asymptomatic or be associated with severe loss of organ function and significant morbidity.
- Treatment with the selective small-molecule Gamma-secretase inhibitor PF-03084014 caused significant tumor shrinkage in patients with unresectable desmoid tumors in an early phase clinical trial.
- The Notch pathway is a key regulator of cell differentiation, proliferation and apoptosis; aberrant signaling via the Notch pathway is associated with carcinogenesis.
Objectives:
- Primary: Determine the response rate (CR+PR) of PF-03084014 in patients with desmoid tumors/aggressive fibromatosis
- Secondary: Assess symptom measures at baseline and on study; perform genotyping for germline and somatic mutations in APC and CTNNB1 genes; correlate clinical response to therapy with genotyping data; and assess modulation of the Notch pathway by evaluating notch response genes in tumor biopsies at baseline and after drug administration
Eligibility:
- Age greater than or equal to18; histologically confirmed desmoid tumor not amenable to curative resection or definitive radiation therapy that has progressed after receiving at least one line of standard treatment; adequate organ function
- Willingness to provide blood samples and 10 unstained slides or a tumor block for genetic research studies
Detailed Summary:
Background:
- Desmoid tumors (also known as aggressive fibromatosis), are rare, locally invasive, slow-growing soft-tissue tumors. The disease can be either asymptomatic or be associated with severe loss of organ function and significant morbidity.
- Treatment with the selective small-molecule Gamma-secretase inhibitor PF-03084014 caused significant tumor shrinkage in patients with unresectable desmoid tumors in an early phase clinical trial.
- The Notch pathway is a key regulator of cell differentiation, proliferation and apoptosis; aberrant signaling via the Notch pathway is associated with carcinogenesis.
Objectives:
- Primary: Determine the response rate (CR+PR) of PF-03084014 in patients with desmoid tumors/aggressive fibromatosis
- Secondary: Assess symptom measures at baseline and on study; perform genotyping for germline and somatic mutations in APC and CTNNB1 genes; correlate clinical response to therapy with genotyping data; and assess modulation of the Notch pathway by evaluating notch response genes in tumor biopsies at baseline and after drug administration
Eligibility:
- Age greater than or equal to18; histologically confirmed desmoid tumor not amenable to curative resection or definitive radiation therapy that has progressed after receiving at least one line of standard treatment; adequate organ function
- Willingness to provide blood samples and 10 unstained slides or a tumor block for genetic research studies
Current Primary Outcome: Determine the response rate (CR+PR) of PF-03084014 in patients with desmoid tumors/aggressive fibromatosis [ Time Frame: Disease progression/recurrence ]
Original Primary Outcome: Determine the response rate (CR+PR) of PF-03084014 in patients with desmoid tumors/aggressive fibromatosis [ Time Frame: 2 years ]
Current Secondary Outcome: Assess symptom measures at baseline and on study; perform genotyping for germline and somatic mutations in APC and CTNNB1 genes; correlate clinical response to therapy with genotyping data; and assess modulation of the Notch pathway by evaluatin... [ Time Frame: Cycle 7 ]
Original Secondary Outcome:
- Correlate clinical response to therapy with genotyping data. [ Time Frame: 2 years ]
- Assess symptoms at baseline/intervals on study. [ Time Frame: 2 years ]
- Perform genotyping for germline and somatic mutations in APC and CTNNB1 genes. [ Time Frame: 2 years ]
Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: October 31, 2013
Date Started: October 25, 2013
Date Completion: December 30, 2018
Last Updated: May 12, 2017
Last Verified: September 27, 2016
