Oral Progestin Tablets With Radiotherapy vs. Standard Radiotherapy and Chemotherapy in High-Risk NSMP Endometrial Cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

In this Phase 3 trial, patients with high-risk NSMP endometrial cancer are randomized to receive radiotherapy with standard chemotherapy or radiotherapy followed by oral progestin tablets. The study aims to see if the oral progestin approach can achieve similar cancer control while lowering toxicity. Eligible participants must have undergone surgery and meet molecular and imaging criteria, with no distant metastases. The intervention compares two adjuvant strategies following surgery to determine non-inferiority in outcomes and potential quality-of-life benefits.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Written informed consent and consent for data sharing for the overarching RAINBO programme
2. Histologically confirmed diagnosis of endometrial cancer (EC) of the following histotypes: endometrioid endometrial carcinoma, serous endometrial carcinoma, uterine clear cell carcinoma, dedifferentiated and undifferentiated endometrial carcinoma, uterine carcinosarcoma and mixed endometrial carcinomas of the aforementioned histotypes
3. Full molecular classification performed following the diagnostic algorithm described in WHO 2020 (5th Edition, IARC, Lyon, 2020, adapted from Vermij et al. 2020)
4. Hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy or sentinel node biopsy, without macroscopic residual disease after surgery
5. No distant metastases as determined by pre-surgical or post-surgical imaging (CT scan of chest, abdomen and pelvis within 8 weeks of randomisation). Whole-body PET-CT scan is acceptable if this is part of standard of care at participating sites
6. Age ≥ 18 years
7. WHO performance status 0 or 1
8. Expected start of adjuvant treatment within 10 weeks after surgery
9. Patients must be accessible for treatment and follow-up
10. Consent for the donation of a tissue block for translational research for the overarching RAINBO programme
11. FIGO (2018) stage II EC with substantial LVSI or stage III NSMP tumours
12. p53 wildtype, MMR proficient EC with no somatic pathogenic POLE variant (i.e. NSMP)
13. ER+ by IHC (10% threshold applied) or Allred score of ≥3
14. Absolute neutrophil count (ANC) ≥1.5 x 109 /l
15. Platelets ≥ 100 x 109 /L
16. Bilirubin ≤ 1.5 x UNL (or ≤ 3 x ULN for cases of known Gilbert's syndrome)
17. AST/ALT ≤ 2.5 x UNL

Exclusion Criteria:

1. Previous malignancy, except for non-melanoma skin cancer, in the past 5 years
2. Prior pelvic radiation
3. Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction) within previous 6 months
4. Thromboembolic event, e.g. pulmonary embolism or deep vein thrombosis, within previous 6 months
5. Impaired renal function: ≤50ml/min (EDTA clearance, or measured creatinine clearance) or creatinine clearance ≤60 ml/min (calculated according to Cockcroft gault)
6. Uncontrolled cardiac disease (defined as cardiac function which would preclude hydration during cisplatin administration and any contraindication to paclitaxel)
7. Peripheral neuropathy, ≥ grade 2
8. Inflammatory bowel disease
9. Known history of porphyria
10. History of active immune deficiency syndromes or uncontrolled HIV infection: HIV positive patients receiving effective antiretroviral therapy and CD4 count \>200 may be included
11. Patients who have received a live attenuated vaccine within 2 weeks prior to planned treatment start
12. Any other condition which as per section 4.3 of the relevant SmPC or in the opinion of the investigator contraindicates the use of chemotherapy, radiotherapy and/or oral progestin tablets
13. The patient is currently participating in another interventional clinical trial or has received an investigational drug (either approved or not approved) in any prior clinical study within 5 half-lives prior to screening

Where it's running

• Royal United Hospitals Bath
  Bath, United Kingdom Recruiting
• Cheltenham General
  Cheltenham, United Kingdom Recruiting
• Leicester Royal Infirmary
  Leicester, United Kingdom Recruiting
• Bartholemew's Hospital
  London, United Kingdom Recruiting
• Royal Marsden (Chelsea)
  London, United Kingdom Recruiting
• University College London Hospital (UCLH)
  London, United Kingdom Recruiting

Study contacts

• Study coordinator: RAINBO NSMP-ORANGE Trial Manager
• Email: ctc.nsmp-orange@ucl.ac.uk
• Phone: +44 2076799808

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.