ROMAN
ROMAN showed that an infusion of avasopasem before each dose of radiotherapy cut severe mouth ulcers during head and neck chemoradiation from about two thirds of patients to about half and shortened them from 18 days to 8, but the effect was smaller than an earlier trial had promised and the FDA asked for another study before approval.
Overview
ROMAN (NCT03689712; organisation id GTI-4419-301) was a double-blind, placebo-controlled phase 3 trial of avasopasem manganese (GC4419), a superoxide dismutase mimetic, in patients with locally advanced head and neck cancer receiving 60 to 72 Gy of intensity-modulated radiotherapy (more than 50 Gy to at least two oral mucosal sites) with cisplatin every three weeks or weekly. Patients were randomised 3:2 to avasopasem 90 mg or placebo before each radiotherapy fraction. Severe oral mucositis (WHO grade 3 or 4) was assessed twice weekly during radiotherapy and weekly for two weeks after; the primary endpoint was its cumulative incidence through the end of radiotherapy.
Of 455 patients randomised, 407 (241 avasopasem, 166 placebo) formed the primary analysis population. Severe oral mucositis occurred in 54 percent on avasopasem versus 64 percent on placebo (relative risk 0.84; 95 percent CI 0.71 to 1.00; p = 0.045), and its median duration was 8 versus 18 days (p = 0.002); onset was nominally delayed (median 49 versus 38 days). Grade 4 mucositis incidence and duration were not significantly reduced (27 percent, p = 0.052; 24 percent, p = 0.143). Adverse-event frequencies were comparable, tumour outcomes were maintained at one year, and two-year overall survival was 89 percent (95 percent CI 84 to 93) with avasopasem versus 93 percent (88 to 96) with placebo.
The eClinicalMedicine 2025 report states that the incidence benefit was smaller than the phase 2b trial had predicted, that a contribution of avasopasem to adverse events could not be excluded, and that ROMAN did not give a sufficiently favourable benefit-risk determination for FDA approval; a confirmatory phase 3 was requested. The FDA issued a complete response letter in August 2023, and the drug remains investigational. The registry condition is oral mucositis rather than a cancer, which is why the automated pass never attached the trial to the drug.
- 54 vs 64 out of 100 reached this endpoint with Avasopasem manganese 90 mg compared with Placebo; 10 fewer per 100.
- On this measure the first group did worse, not better.
- The p-value (0.045) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
- This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
- Avasopasem manganese 90 mg: 8 days; Placebo: 18 days.
- The p-value (0.002) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
- This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
- Avasopasem manganese 90 mg: 49 days; Placebo: 38 days.
- This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
- 89 vs 93 out of 100 alive at 2 years with Avasopasem manganese 90 mg compared with Placebo; 4 fewer per 100.
- On this measure the first group did worse, not better.
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- These results apply to the people the trial enrolled: Locally advanced, non-metastatic head and neck cancer receiving intensity-modulated radiotherapy plus cisplatin: avasopasem manganese 90 mg versus placebo infused before each radiotherapy fraction, randomised 3:2. People in a different situation may not see the same effect.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
455 enrolled.
Relative risk 0.84 vs placebo; 95% CI 0.71 to 1.00
Source95% CI 84 to 93; tumour outcomes were maintained at one year · 95% CI 88 to 96
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Severe oral mucositis (WHO grade 3 or 4) incidence through the end of radiotherapyprimary | Avasopasem manganese 90 mg | 241 | 54% | - | 0.045 | link |
| Placebo | 166 | 64% | ||||
| Median duration of severe oral mucositis | Avasopasem manganese 90 mg | 241 | 8 days | - | 0.002 | link |
| Placebo | 166 | 18 days | ||||
| Median time to onset of severe oral mucositis | Avasopasem manganese 90 mg | 241 | 49 days | - | - | link |
| Placebo | 166 | 38 days | ||||
| Overall survival at 2 years | Avasopasem manganese 90 mg | - | 89% | - | - | link |
| Placebo | - | 93% |
Similar pages
not linked directly; found by shared links- TermRadiation dermatitis (skin reaction)
Shares Radioprotectors and normal-tissue sparing drugs, Head and neck squamous cell carcinoma.
- TreatmentAmifostine
Shares Radioprotectors and normal-tissue sparing drugs, Head and neck squamous cell carcinoma.
- TreatmentPilocarpine
Shares Radioprotectors and normal-tissue sparing drugs, Head and neck squamous cell carcinoma.