Endometrial CancerPhase 3NSMP-ORANGENCT07831902
Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features (RAINBO) - NSMP-ORANGE Trial: Comparing Radiotherapy With Oral Progestin Tablets vs. the Current Standard Care, Radiotherapy and Chemotherapy, in Patients With NSMP Endometrial Cancer
A Phase 3 study testing medroxyprogesterone acetate tablets OR megestrol acetate, Cisplatin and Carboplatin + Paclitaxel in people with Endometrial Cancer and Uterine Neoplasms, run by University College, London at 12 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometrial Cancer, Uterine Neoplasms
- What is being tested?
- medroxyprogesterone acetate tablets OR megestrol acetate, Cisplatin and Carboplatin + Paclitaxel
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 600 participants
- Where
- 12 sitesUnited Kingdom
- Study dates
- 29 Jun 2026to Dec 2034
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent and consent for data sharing for the overarching RAINBO programme
- 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
- Full molecular classification performed following the diagnostic algorithm described in WHO 2020 (5th Edition, IARC, Lyon, 2020, adapted from Vermij et al. 2020)
- Hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy or sentinel node biopsy, without macroscopic residual disease after surgery
- 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
- Age ≥ 18 years
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- WHO performance status 0 or 1
- Expected start of adjuvant treatment within 10 weeks after surgery
- Patients must be accessible for treatment and follow-up
- Consent for the donation of a tissue block for translational research for the overarching RAINBO programme
- FIGO (2018) stage II EC with substantial LVSI or stage III NSMP tumours
- p53 wildtype, MMR proficient EC with no somatic pathogenic POLE variant (i.e. NSMP)
- ER+ by IHC (10% threshold applied) or Allred score of ≥3
- Absolute neutrophil count (ANC) ≥1.5 x 109 /l
- Platelets ≥ 100 x 109 /L
- Bilirubin ≤ 1.5 x UNL (or ≤ 3 x ULN for cases of known Gilbert's syndrome)
- AST/ALT ≤ 2.5 x UNL
Who cannot join
- Previous malignancy, except for non-melanoma skin cancer, in the past 5 years
- Prior pelvic radiation
- Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction) within previous 6 months
- Thromboembolic event, e.g. pulmonary embolism or deep vein thrombosis, within previous 6 months
- Impaired renal function: ≤50ml/min (EDTA clearance, or measured creatinine clearance) or creatinine clearance ≤60 ml/min (calculated according to Cockcroft gault)
- Uncontrolled cardiac disease (defined as cardiac function which would preclude hydration during cisplatin administration and any contraindication to paclitaxel)
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- Peripheral neuropathy, ≥ grade 2
- Inflammatory bowel disease
- Known history of porphyria
- History of active immune deficiency syndromes or uncontrolled HIV infection: HIV positive patients receiving effective antiretroviral therapy and CD4 count >200 may be included
- Patients who have received a live attenuated vaccine within 2 weeks prior to planned treatment start
- 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
- 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
Trial locations and contacts
12 sites in 1 country. Contact the study team or a site near you to ask about taking part.
12 sites in 1 country
United Kingdom12 sites, 12 recruiting
- Recruiting
Royal United Hospitals Bath
Bath
Jennifer Van Griethuysen
- Recruiting
Cheltenham General
Cheltenham
Audrey Cook
- Recruiting
Leicester Royal Infirmary
Leicester
Anupama Gore
- Recruiting
Bartholemew's Hospital
London
Millie Light
- Recruiting
Royal Marsden (Chelsea)
London
Alexandra Taylor
- Recruiting
University College London Hospital (UCLH)
London
Gemma Eminowicz
- Recruiting
The Christie
Manchester
Andrew Clamp
- Recruiting
James Cook University Hospital
Middlesbrough
Darren Leaning
- Recruiting
Churchill
Oxford
Sally Trent
- Recruiting
Queen Alexandra Hospital
Portsmouth
Radwa Ahmed
- Recruiting
University Hospital Southampton
Southampton
Vicky McFarlane
- Recruiting
Royal Marsden (Sutton)
Sutton
Alexandra Taylor
About this study
Official title: Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features (RAINBO) No Specific Molecular Profile (NSMP) - ORANGE Trial
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.
- Conditions
- Endometrial Cancer, Uterine Neoplasms
- Being tested
- medroxyprogesterone acetate tablets OR megestrol acetate, Cisplatin, Carboplatin + Paclitaxel
- 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
- Medical subject headings
- Endometrial Neoplasms, Uterine Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
medroxyprogesterone acetate tablets OR megestrol acetateDrug
Also called oral progestin
Medroxyprogesterone acetate 200mg once daily OR megestrol acetate 160mg once daily following completion of radiotherapy, for 24 months (2 years)
CisplatinDrug
carboplatin and paclitaxel +/- cisplatin, as per standard of care/investigator decision, with radiotherapy
Carboplatin + PaclitaxelDrug
carboplatin and paclitaxel +/- cisplatin, as per standard of care/investigator decision, with radiotherapy
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Adjuvant pelvic radiotherapy +/- vaginal brachytherapy followed by oral progestin tablets for 24 months (investigational arm) Receives: Drug: medroxyprogesterone acetate tablets OR megestrol acetate |
| Arm B | Active comparator | Adjuvant pelvic radiotherapy +/- vaginal brachytherapy with chemotherapy (cisplatin, carboplatin and paclitaxel, standard of care arm) Receives: Drug: Cisplatin; Drug: Carboplatin + Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence free survival (RFS)
RFS is defined as the time from date of randomisation to date of recurrence or death from any cause.
Measured: 3 years
Secondary outcomes (9)
Recurrence free survival (RFS)
RFS is defined as the time from date of randomisation to date of recurrence or death from any cause.
Measured: 5 years
Vaginal recurrence free survival (RFS)
Defined as the time from date of randomisation to date of vaginal recurrence.
Measured: 3 years, 5 years
Pelvic recurrence free survival (RFS)
Defined as the time from date of randomisation to date of pelvic recurrence.
Measured: 3 years, 5 years
Para-aortic nodal recurrence free survival (RFS)
Defined as the time from date of randomisation to date of para-aortic nodal recurrence
Measured: 3 years, 5 years
Distant recurrence free survival (RFS)
Defined as the time from date of randomisation to date of distant recurrence
Measured: 3 years, 5 years
Cancer-specific survival
Defined as the time from date of randomisation to date of cancer-related death
Measured: 3 years, 5 years
Overall survival
Defined as the time from date of randomisation to date of death from any cause
Measured: 3 years, 5 years
Treatment-related toxicity (using the Common Terminology Criteria for Adverse Events [CTCAE] version 5.0)
Toxicity at any time will be described by trial arm in the safety population which will include all patients who receive any trial treatment.
Measured: 3 years, 5 years
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)
Measured: 3 years, 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2026
- Study start29 Jun 2026
- Primary completionDec 2030 (estimated)
- Study completionDec 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endometrial CancerStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07831902
- Sponsor's protocol ID
- UCL141703
- Other IDs
- 1007892
- Acronym
- NSMP-ORANGE
- Status last verified
- Sep 2026
- First submitted
- 15 Sep 2026
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Following the planned translational work in the RAINBO programme and publications, the translational research (TR) committee will open up the sample collection to external researchers. Access will be granted following completion of a research proposal form and approval by the TR committee chaired by Dr. Tjalling Bosse. All external researchers will be expected to demonstrate funding for their project and ethics approval. Data will be made available as required through data sharing agreements. The following will be reviewed when considering applications for data sharing and sample access: data and sample use is in-keeping with patient consent, the proposed project has scientific value, with defined objectives and study plan, trial data are appropriate for the intended purpose, acknowledgement of the RAINBO Programme in all publications that arise from the data sharing, compliance with legal and regulatory requirements as applicable and patient confidentiality maintained at all times.
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features (RAINBO) No Specific Molecular Profile (NSMP) - ORANGE Trial
- ClinicalTrials.gov ID
- NCT07831902
- Acronym / sponsor ID
- NSMP-ORANGE / UCL141703
- Conditions
- Endometrial Cancer, Uterine Neoplasms
- Keywords
- NSMP, oral progestin, endometrial cancer, no specific molecular profile, womb cancer, hormone tablets, hormone therapy, uterine cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- 29 Jun 2026 (actual)
- Primary completion
- Dec 2030 (estimated)
- Study completion
- Dec 2034 (estimated)
- First posted
- 21 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: medroxyprogesterone acetate tablets OR megestrol acetateAdjuvant pelvic radiotherapy +/- vaginal brachytherapy followed by oral progestin tablets for 24 months (investigational arm) |
| Arm B | Active comparator | Drug: Cisplatin, Drug: Carboplatin + PaclitaxelAdjuvant pelvic radiotherapy +/- vaginal brachytherapy with chemotherapy (cisplatin, carboplatin and paclitaxel, standard of care arm) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Written informed consent and consent for data sharing for the overarching RAINBO programme
- 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
- Full molecular classification performed following the diagnostic algorithm described in WHO 2020 (5th Edition, IARC, Lyon, 2020, adapted from Vermij et al. 2020)
- Hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy or sentinel node biopsy, without macroscopic residual disease after surgery
- 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
Key exclusion criteria (13 listed)
- Previous malignancy, except for non-melanoma skin cancer, in the past 5 years
- Prior pelvic radiation
- Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction) within previous 6 months
- Thromboembolic event, e.g. pulmonary embolism or deep vein thrombosis, within previous 6 months
- Impaired renal function: ≤50ml/min (EDTA clearance, or measured creatinine clearance) or creatinine clearance ≤60 ml/min (calculated according to Cockcroft gault)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| medroxyprogesterone acetate tablets OR megestrol acetateAlso: oral progestinMedroxyprogesterone acetate 200mg once daily OR megestrol acetate 160mg once daily following completion of radiotherapy, for 24 months (2 years) | Drug | Arm A |
| Cisplatincarboplatin and paclitaxel +/- cisplatin, as per standard of care/investigator decision, with radiotherapy | Drug | Arm B |
| Carboplatin + Paclitaxelcarboplatin and paclitaxel +/- cisplatin, as per standard of care/investigator decision, with radiotherapy | Drug | Arm B |
Primary outcome
Recurrence free survival (RFS)
Time frame: 3 years
RFS is defined as the time from date of randomisation to date of recurrence or death from any cause.
9 secondary outcomes
Recurrence free survival (RFS)
Time frame: 5 years
Vaginal recurrence free survival (RFS)
Time frame: 3 years, 5 years
Pelvic recurrence free survival (RFS)
Time frame: 3 years, 5 years
Para-aortic nodal recurrence free survival (RFS)
Time frame: 3 years, 5 years
Distant recurrence free survival (RFS)
Time frame: 3 years, 5 years
Cancer-specific survival
Time frame: 3 years, 5 years
Overall survival
Time frame: 3 years, 5 years
Treatment-related toxicity (using the Common Terminology Criteria for Adverse Events [CTCAE] version 5.0)
Time frame: 3 years, 5 years
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)
Time frame: 3 years, 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Individual participant dataSharing planned: Yes. Following the planned translational work in the RAINBO programme and publications, the translational research (TR) committee will open up the sample collection to external researchers. Access will be granted following completion of a research proposal form and approval by the TR committee chaired by Dr. Tjalling Bosse. All external researchers will be expected to demonstrate funding for their project and ethics approval. Data will be made available as required through data sharing agreements. The following will be reviewed when considering applications for data sharing and sample access: data and sample use is in-keeping with patient consent, the proposed project has scientific value, with defined objectives and study plan, trial data are appropriate for the intended purpose, acknowledgement of the RAINBO Programme in all publications that arise from the data sharing, compliance with legal and regulatory requirements as applicable and patient confidentiality maintained at all times.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing medroxyprogesterone acetate tablets OR megestrol acetate, Cisplatin and Carboplatin + Paclitaxel in people with Endometrial Cancer and Uterine Neoplasms, run by University College, London at 12 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact RAINBO NSMP-ORANGE Trial Manager (+44 2076799808, ctc.nsmp-orange@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence free survival (RFS) (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.