# Intermittent or stop-and-restart nirogacestat in desmoid tumours

Source: https://onco.cc/ideas/idea-desmoid-intermittent-dosing/  
OnCo record `idea-desmoid-intermittent-dosing` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Desmoid tumours are not cancers and often stop growing on their own; treating them indefinitely with a drug that causes ovarian failure may be more than needed.

## Summary

Desmoid tumours are not cancers, do not metastasise and often stop growing on their own, yet nirogacestat, tested in the DeFi trial, is given continuously and causes ovarian failure. This idea proposes treating to best response, then pausing the drug and restarting only on progression. DeFi showed durable responses and ovarian toxicity that reverses when the drug is stopped, and a debate in JCO in 2026 has questioned long-term continuous use; the rationale is that toxicity depends on dose and duration and is reversible. The proposed test is a randomised discontinuation trial after twelve months of response with time to progression and ovarian function as co-primary endpoints; the idea is speculative and addresses the bottleneck of wrong doses, alongside the adaptive-therapy platform idea.

## Fields

- Kind: Idea
- Last checked: 2026-09-07
- Hypothesis: Treatment to best response followed by a drug holiday with restart on progression preserves disease control and fertility with fewer adverse events.
- Rationale: Slow-growing, non-metastasising tumour; toxicity is dose-duration dependent and reversible.
- Proposed test: Randomised discontinuation trial after 12 months of response; time to progression and ovarian function as co-primary.
- Maturity: speculative

## Sources

- ClinicalTrials.gov NCT03785964: DeFi: https://clinicaltrials.gov/study/NCT03785964

## Connected records

- cancers: [Desmoid tumour](https://onco.cc/cancers/desmoid-tumour/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/)
- drugs: [Nirogacestat](https://onco.cc/drugs/nirogacestat/)
- trials: [DeFi](https://onco.cc/trials/defi/)
- bottlenecks: [Wrong doses](https://onco.cc/bottlenecks/b-dose-optimisation/)
- ideas: [A multi-cancer platform trial of adaptive (dose-holiday) therapy](https://onco.cc/ideas/idea-bio1-adaptive-therapy-platform/)

---
JSON: https://onco.cc/api/v1/entities/idea-desmoid-intermittent-dosing.json