Recruiting PHASE2, PHASE3 Endometrial Cancer

New treatment option for Endometrial Cancer

Official title Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features

ClinicalTrials.gov ID: NCT05255653

What this study is testing

What is Olaparib?

Olaparib is an investigational medicine, given as an once-daily, being studied as a potential treatment for endometrial cancer.

Also referred to as Lynparza.

Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.

What it's testing: The RAINBO umbrella program consists of four clinical trials investigating new adjuvant therapies in endometrial cancer patients. Eligible patients will be assigned to one of the four RAINBO trials based on the molecular profile of their cancer: p53 abnormal endometrial cancer patients to the p53abn-RED trial mismatch repair deficient endometrial cancer patients to the MMRd-GREEN trial no specific molecular profile endometrial cancer patients to NSMP-ORANGE trial POLE mutant endometrial cancer patients to the POLEmut-BLUE trial

Phase 3: a large, late-stage study
Which group you join is decided by chance.

A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.

Who can take part

Ages 18 and older, women only

You may be able to join if

Participants of the four RAINBO trials should be eligible according to the inclusion and

You likely can't join if

of both the overarching RAINBO trials program and the clinical trial that they are assigned to based on the molecular profile. Inclusion Criteria of...
Histologically confirmed diagnosis of endometrial cancer (EC) of the following histotypes: endometrioid endometrial carcinoma, serous endometrial...
Full molecular classification performed following the diagnostic algorithm described in WHO 2020 (5th Edition, IARC, Lyon, 2020)
Hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy or sentinel node biopsy, without macroscopic residual disease after...
No distant metastases as determined by pre-surgical or post-surgical imaging (CT scan of chest, abdomen and pelvis or whole-body PET-CT scan)
WHO performance status 0, 1 or 2

See the full eligibility criteria

Who can join

Participants of the four RAINBO trials should be eligible according to the inclusion and

What rules you out

of both the overarching RAINBO trials program and the clinical trial that they are assigned to based on the molecular profile. Inclusion Criteria of the overarching RAINBO program:
Histologically confirmed diagnosis of endometrial cancer (EC) of the following histotypes: endometrioid endometrial carcinoma, serous endometrial carcinoma, uterine clear cell carcinoma, dedifferentiated and...
Full molecular classification performed following the diagnostic algorithm described in WHO 2020 (5th Edition, IARC, Lyon, 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 or whole-body PET-CT scan)
WHO performance status 0, 1 or 2
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...
History of another primary malignancy, except for non-melanoma skin cancer, in the past 5 years
Prior pelvic radiation The p53abn-RED trial Inclusion criteria:
p53 abnormal EC
Histologically confirmed stage I (with invasion) II or III EC
WHO Performance score 0-1
Body weight \> 30 kg
Adequate systemic organ function:
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...
Adequate bone marrow function : hemoglobin \>9.0 g/dl, Absolute neutrophil count (ANC) ≥1.0 x 109/l, platelet count ≥75 x 109/l.
Adequate liver function: bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly...
Pathogenic POLE mutation(s)
Mismatch repair deficiency
Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of the 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...
Any previous treatment with a PARP inhibitor, including olaparib
History of active primary immunodeficiency
History or evidence of hemorrhagic disorders within 6 months prior to randomization
Patients with myelodysplastic syndrome/acute myeloid leukemia history or with features suggestive of MDS/AML
Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
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...
Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or...
Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz...
Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
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. The MMRd-GREEN trial Inclusion criteria:
Mismatch repair deficient EC
Histologically confirmed (FIGO 2009) stage IB/II EC with myometrial or cervical stroma involvement and lympovascular space invasion (LVSI) OR Stage III EC OR Stage IVA with limited pelvic peritoneal involvement
WHO Performance score 0-1
Body weight \> 30 kg
Adequate systemic organ function:
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...
Adequate bone marrow function : hemoglobin \>9.0 g/dl, Absolute neutrophil count (ANC) ≥1.0 x 109/l, platelet count ≥75 x 109/l.
Adequate liver function: bilirubin ≤1.5 x institutional upper limit of normal (ULN). \ \> AND ALT (SGPT) and/or AST (SGOT) ≤2.5 x ULN Exclusion criteria:
Pathogenic POLE mutation(s)
Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational medicinal product (IMP)
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...
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 IMP.
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 \ \> 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...
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...
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. The NSMP-ORANGE trial Inclusion criteria:
NSMP EC
Histologically confirmed stage II EC with substantial LVSI or stage III EC
ER positive EC
WHO performance status 0-1 Exclusion criteria:
Pathogenic POLE mutation(s)
Mismatch repair deficiency
p53 abnormality The POLEmut-BLUE trial Inclusion criteria:
Pathogenic POLE mutation(s)
For the main cohort, patients must have one of the following combinations of FIGO stage, grade, and LVSI:
stage IA (not confined to polyp), grade 3, pN0, with or without LVSI
stage IB, grade 1 or 2, pNx/N0, with or without LVSI
stage IB, grade 3, pN0, without substantial LVSI
stage II (microscopic), grade 1 or 2, pN0, without substantial LVSI
For the exploratory cohort, patients must have one of the following combinations of FIGO stage, grade, and LVSI:
stage IA (not confined to polyp), grade 3 - Stage III not included in main cohort
Multiple molecular classifiers stage IA (not confined to polyp), grade 3 - Stage III
Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrolment in the trial to document their willingness to...
Patient is able (i.e., sufficiently fluent) and willing to complete the QOL and/or health utility questionnaires in either English, French or a validated language. The baseline assessment must be completed within the...
Patients must be accessible for treatment and follow up. Patients enrolled on this trial must be treated and followed at the participating center. Investigators must assure themselves the patients enrolled on this trial...
Patients must agree to return to their primary care facility for any adverse events which may occur through the course of the trial.
In accordance with CCTG policy, protocol treatment is to begin within 10 weeks of hysterectomy/bilateral salpingo-oophorectomy. Exclusion criteria:
Prior chemotherapy for EC
Isolated tumor cells identified in lymph node(s) for main study cohort (patient can be included in exploratory cohort)

The study team makes the final eligibility decision.

Where it's taking place

Toronto, Canada
Vancouver, Canada
Villejuif, France
Amsterdam, Netherlands
Breda, Netherlands
Eindhoven, Netherlands
Enschede, Netherlands
Groningen, Netherlands
Leiden, Netherlands
Rotterdam, Netherlands
The Hague, Netherlands
London, United Kingdom
Manchester, United Kingdom

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling female, 18 years and older. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Toronto, Canada; Vancouver, Canada; Villejuif, France; Amsterdam, Netherlands; Breda, Netherlands; Eindhoven, Netherlands and 7 more location(s). Enter your location above to see the nearest site and check your eligibility.

Explore other conditions

Obesity Type 2 diabetes Type 1 diabetes Prediabetes Weight loss Metabolic syndrome High cholesterol High triglycerides High blood pressure PCOS Hypothyroidism Thyroid disease Gout Fatty liver disease (NAFLD/NASH)Heart failure Coronary artery disease

BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.