Phase II Trial of the Gamma-Secretase Inhibitor PF-03084014 in Adults With Desmoid Tumors/Aggressive Fibromatosis


  • 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.



  • 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



  • 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


Study Design:

  • This is an open-label Phase II trial of PF-03084014; study drug will be administered orally at 150 mg twice a day in 21-day cycles
  • Optional tumor biopsies for research purposes will be performed at baseline prior to study treatment and at the beginning of cycle 7 (+/- one cycle)
  • Restaging scans (MRI with diffusion weighting) will be performed at baseline, at the end of cycles 1 and 6, and then every 6 cycles
  • Health-related quality of life (HRQOL)/symptom questionnaires will be administered at baseline and at each Clinical Center visit