Nirogacestat for Adults With Desmoid Tumour/Aggressive Fibromatosis (DT/AF)

Official Title

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Nirogacestat Versus Placebo in Adult Patients With Progressing Desmoid Tumours/Aggressive Fibromatosis (DT/AF)


This study evaluates nirogacestat in the treatment of desmoid tumour/aggressive fibromatosis (DT/AF). Half of the participants will receive nirogacestat while the other half will receive placebo.

Trial Description

Primary Outcome:

  • Number of progression free survival (PFS) events as defined as the time from randomization until date of assessment of progression or death by any cause.
Secondary Outcome:
  • The incidence of adverse events (AEs) according to toxicities graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
  • Overall response rate using RECIST Version 1.1 criteria.
  • Duration of response for participants whose best response is CR or PR.
  • Tumour volume changes from baseline as measured by MRI volumetric.
  • Change from baseline in patient reported outcome (PRO) scores using the GOunder/Desmoid Tumour Research Tumour Foundation (DTRF) DEsmoid Symptom Scale (GODDESS);.
  • Change from baseline in PRO scores using the Brief Pain Inventory (BPI) short form.
  • Change in baseline in PRO scores using the Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS PF) short form 10a plus 3 additional items from PROMIS item banks.
  • Change from baseline in PRO scores using the GOunder/Desmoid Tumour Research Tumour Foundation (DTRF) DEsmoid Impact Scale (GODDESS);
  • Change from baseline in PRO scores using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC) QLQ-C30.
Desmoid tumours, also referred to as aggressive fibromatosis, are rare, locally invasive, slow growing soft tissue tumours. Although considered benign because of their inability to metastasize, desmoid tumours can cause significant morbidity and occasionally mortality in patients. Nirogacestat (PF-03084014) is a potent, small molecule, selective, reversible, noncompetitive inhibitor of γ-secretase (GS) with a potential antitumour activity. Nirogacestat is being investigated for the treatment of desmoid tumours due to its ability to bind to GS, blocking proteolytic activation of Notch receptors. Previous clinical study data have shown that Notch signaling plays an important role in cancer development. Hence, inhibition of Notch signaling is an important strategy for therapeutic treatment.

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Canadian Cancer Society

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