RAINBO: Refining Adjuvant treatment IN endometrial cancer Based On molecular features, The MMRD-GREEN trial
- Conditions
- Endometrial CancerTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-000518-40-NL
- Lead Sponsor
- eiden University Medical Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 316
Key inclusion criteria for 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 II EC with substantial LVSI
•Molecular classification: MMRd EC*
•No prior pelvic radiotherapy
•Body weight > 30 kg
•Adequate systemic organ function:
oCreatinine 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.
oAdequate bone marrow function : hemoglobin >9.0 g/dl, Absolute neutrophil count (ANC) =1.0 x 109/l, platelet count =75 x 109/l.
oAdequate liver function:
•bilirubin =1.5 x institutional upper limit of normal (ULN). <>
•ALT (SGPT) and/or AST (SGOT) =2.5 x ULN
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 158
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 158
•History of another primary malignancy that could conceivably be active evaluated by the study physician. Examples of exception include, but are not limited to
-Malignancy treated with curative intent and with no known active disease =5 years before the first dose of IP and of low potential risk for recurrence.
-Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
•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 PD(L)1 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.
•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 clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 3 year recurrence free survival (RFS), in patients with MMRd HREC;Secondary Objective: •RFS (median and at 5 years)<br> •Vaginal RFS, pelvic RFS, distant metastasis free-survival (median, 3-year, 5-year)<br> •Disease-specific survival (median, 3-year, 5-year)<br>• OS (median, 3yr, 5yr)<br>• HRQoL<br>• Safety & tolerability (NCI-CTC grade 3-5)<br>• Exploratory translational research (TR), including PD-L1 testing using SP263 assay and TIP algorithm (>1% and 5%) on biopsy or resections of EC samples.<br>;Primary end point(s): 3 year recurrence free survival.<br>RFS is defined as time from randomization until date of any recurrence (local or distant) or date of death due to any cause, whichever occurred first.<br>;Timepoint(s) of evaluation of this end point: 3 years
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Investigator assessed median and 5 yr RFS<br>2. Vaginal RFS, pelvic RFS, distant metastasis free-survival (median, 3-year, 5-year)<br>3. Disease-specific survival (median, 3-year, 5-year)<br>4. Overall Survival (OS) (median, 3yr, 5yr)<br>5. HRQoL (EORTC QLQC30 and QLQEN24) <br>6. Safety & tolerability, grade 3-5 according to NCI-CTC version 5.0.<br>7. Exploratory TR, including PD-L1 testing using SP263 assay (>1% and 5%) on biopsy or resections of EC<br>samples;Timepoint(s) of evaluation of this end point: ad 1) at 5 years<br>ad2) At mortality <br>ad 3) at baseline and months 2,6,12,18, 24, 36, 48, and 60.<br>ad 4) During theray and till 30 days thereafter<br>ad 5) between year 3 and 5