NSMP ORANGE Trial
Research type
Research Study
Full title
Refining Adjuvant treatment IN endometrial cancer Based On molecular features (RAINBO) No Specific Molecular Profile (NSMP)-ORANGE Trial
IRAS ID
1007892
Contact name
Ian Macdonald
Contact email
Sponsor organisation
University College London
Clinicaltrials.gov Identifier
NCT05255653-3
Research summary
Womb cancer is the most common gynaecological cancer in the UK. Most patients present early and are cured by hysterectomy, however some are at risk of the cancer returning and need additional treatment. Decisions about additional treatment are based on tumour spread and appearance under the microscope. This is imprecise and patients must balance the risk of cancer recurrence and death with treatment-related harms.
Womb cancers can now be classified into four groups based on molecular profile that closely link to risk of recurrence. These are p53-abnormal, with the poorest outcome (~50% of patients are cancer-free at 5 years); mismatch repair-deficient (MMRd) and those with no specific molecular profile (NSMP), with intermediate outcomes (~70-75% cancer-free at 5 years); and POLE-mutant, with excellent outcomes (>97% cancer-free at 5 years).
The RAINBO programme will use the newly described molecular groups to individualise treatment for women with high-risk womb cancer. RAINBO is a new generation multi-arm biomarker-directed treatment programme that will evaluate personalised womb cancer therapy. We will see whether treatment based on molecular group reduces cancer recurrence whilst minimising harms from unnecessary chemotherapy.
High-risk womb cancer patients from hospital sites will be recruited after their hysterectomy. Molecular testing will establish whether tumours are p53-abnormal, MMRd, POLE-mutant or NSMP and patients will enter one of four RAINBO trials according to the molecular profile of their tumour. In the UK-led RAINBO NSMP-ORANGE trial for patients with hormone -sensitive NSMP endometrial cancer we will test whether oral progestin tablets for two years is comparable to standard chemotherapy in patients treated by hysterectomy and radiotherapy, and whether treatment-related harms and quality of life differ. We will collect NSMP tumours for the RAINBO translational research programme.
REC name
London - Hampstead Research Ethics Committee
REC reference
25/LO/0444
Date of REC Opinion
17 Jul 2025
REC opinion
Further Information Favourable Opinion