Endometrial Cancer, Uterine Neoplasms
Conditions
Keywords
NSMP, oral progestin, endometrial cancer, no specific molecular profile, womb cancer, hormone tablets, hormone therapy, uterine cancer, progestin, Molecular risk factors, Chemoradiation, Radiotherapy, Chemotherapy
Brief summary
RAINBO NSMP-ORANGE aims to investigate if adjuvant radiotherapy with oral progestin tablets is as effective as radiotherapy with chemotherapy, whilst reducing toxicity and thus improving quality of life, in patients with high-risk NSMP endometrial cancer. Patients will be randomised to radiotherapy with chemotherapy (standard of care), or radiotherapy followed by oral progestin tablets.
Interventions
Medroxyprogesterone acetate 200mg once daily OR megestrol acetate 160mg once daily following completion of radiotherapy, for 24 months (2 years)
DRUGCisplatin
carboplatin and paclitaxel +/- cisplatin, as per standard of care/investigator decision, with radiotherapy
carboplatin and paclitaxel +/- cisplatin, as per standard of care/investigator decision, with radiotherapy
Sponsors
University College, London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence free survival (RFS) | 3 years | RFS is defined as the time from date of randomisation to date of recurrence or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence free survival (RFS) | 5 years | RFS is defined as the time from date of randomisation to date of recurrence or death from any cause. |
| Vaginal recurrence free survival (RFS) | 3 years, 5 years | Defined as the time from date of randomisation to date of vaginal recurrence. |
| Pelvic recurrence free survival (RFS) | 3 years, 5 years | Defined as the time from date of randomisation to date of pelvic recurrence. |
| Para-aortic nodal recurrence free survival (RFS) | 3 years, 5 years | Defined as the time from date of randomisation to date of para-aortic nodal recurrence |
| Distant recurrence free survival (RFS) | 3 years, 5 years | Defined as the time from date of randomisation to date of distant recurrence |
| Cancer-specific survival | 3 years, 5 years | Defined as the time from date of randomisation to date of cancer-related death |
| Overall survival | 3 years, 5 years | Defined as the time from date of randomisation to date of death from any cause |
| Treatment-related toxicity (using the Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) | 3 years, 5 years | Toxicity at any time will be described by trial arm in the safety population which will include all patients who receive any trial treatment. |
| Health-related quality of life (using the validated common and endometrial cancer European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaires C30 and EN24) | 3 years, 5 years | — |
Countries
United Kingdom
Contacts
CONTACTRAINBO NSMP-ORANGE Trial Manager
Outcome results
None listed