RAINBO: Refining Adjuvant treatment IN endometrial cancer Based On molecular features, MMRd-GREEN trial

Phase 3

Recruiting

Conditions: Endometrial cancer inclusive carcinosarcoma of the endometrium
10038594

Registration Number: NL-OMON54178

Lead Sponsor: eids Universitair Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 150

Inclusion Criteria

Inclusion criteria for the RAINBO program:
• Histologically confirmed diagnosis of EC of the following histologic
subtypes: 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)
• TLH-BSO or TAH-BSO with or without lymphadenectomy and/or full surgical
staging, without macroscopic residual disease after surgery
• No distant metastases as determined by pre-surgical or post-surgical imaging
(CT/MRI scan of chest, abdomen and pelvis or PET-CT scan)
• Age > 18 years
• Expected start of adjuvant treatment (if applicable) within 10 weeks after
surgery
• Patients must be accessible for treatment and follow-up
• Written informed consent for participation in one of the RAINBO trials,
permission for the contribution of a tissue block for translation research and
permission for the use and sharing of data for the overarching research project
according to the local Ethics Committee requirements.

Inclusion criteria specific for MMRD-Green trial:
• Written informed consent
• WHO Performance score 0-1
• Histologically confirmed Stage III EC or stage IB/II EC with substantial LVSI
• Molecular classification: MMRd EC
• No prior pelvic radiotherapy
• Body weight > 30 kg
• Adequate systemic organ function:
o Creatinine clearance (> 40 cc/min): Measured creatinine clearance (CL) >40
mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula
(Cockcroft and Gault 1976) or by 24-hour urine collection for determination of
creatinine clearance.
o Adequate bone marrow function : hemoglobin >9.0 g/dl, Absolute neutrophil
count (ANC) >=1.0 x 109/l, platelet count >=75 x 109/l.
o Adequate liver function:
• bilirubin <=1.5 x institutional upper limit of normal (ULN). <apply to patients with confirmed Gilbert*s syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of
hemolysis or hepatic pathology), who will be allowed only in consultation with
their physician.>>
• ALT (SGPT) and/or AST (SGOT) <=2.5 x ULN

Exclusion Criteria

Exclusion criteria for RAINBO program
• History of another primary malignancy, except for non-melanoma skin cancer,
in the past 5 years
• Prior pelvic irradiation

Exclusion criteria specific for MMRd-GREEN trial:
• Major surgical procedure (as defined by the Investigator) within 28 days
prior to the first dose of IP.
• History of allogenic organ transplantation.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or
active infection, symptomatic congestive heart failure, uncontrolled
hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung
disease, serious chronic gastrointestinal conditions associated with diarrhea,
or psychiatric illness/social situations that would limit compliance with study
requirement, substantially increase risk of incurring AEs or compromise the
ability of the patient to give written informed consent.
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
• Receipt of live attenuated vaccine within 30 days prior to the first dose of
durvalumab. Note: Patients, if enrolled, should not receive live vaccine whilst
receiving IP and up to 30 days after the last dose of IP.
• Current or prior use of immunosuppressive medication within 14 days before
the first dose of durvalumab with the exceptions of :
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g.,
intra articular injection).
- Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of
prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication).
• History of active primary immunodeficiency
• Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis
[with the exception of diverticulosis], systemic lupus erythematosus,
Sarcoidosis syndrome, or Wegener syndrome. The following are exceptions to this
criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome)stable on
hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only
after consultation with the study physician.
• Active infection including tuberculosis (clinical evaluation that includes
clinical history, physical examination and radiographic findings, and TB
testing in line with local practice), hepatitis B (known positive HBV surface
antigen (HBsAg) result), hepatitis C, or human immuno-deficiency virus
(positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection
(defined as the presence of hepatitis B core antibody [anti-HBc] and absence of
HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are
eligible only if polymerase chain reaction is negative for HCV RNA.
• Known allergy for durvalumab.
• Medical or psychological condition which in the opinion of the investigator
would not permit the patient to complete the study or sign meaningful informed
consent.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>3 year recurrence free survival (RFS) in patients with MMRd EC.<br /><br>RFS is defined as time from randomization until date of any recurrence (local<br /><br>or distant) or date of death due to any cause.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Investigator assessed 5 yr RFS<br /><br>- OS (median, 3yr, 5yr)<br /><br>- Vaginal RFS, pelvic RFS, distant metastasis free-survival (median,<br /><br>3-year, 5-year)<br /><br>- Disease-specific survival (median, 3-year, 5-year)<br /><br>- HRQoL (EORTC QLQC30 and EORTC QLQEN24)<br /><br>- Safety & tolerability, grade 3-5 according to NCI-CTC version 5.0.<br /><br>- Exploratory TR, including PD-L1 testing using SP263 assay and TIP algorithm<br /><br>(>1% and 5%) on biopsy or resections of EC samples</p><br>