Informations générales (source: ClinicalTrials.gov)
Randomized Phase III Trial Testing Maintenance Olaparib Versus Observation After Adjuvant Chemoradiation for P53abn Endometrial Cancer
Interventional
Phase 3
Gustave Roussy, Cancer Campus, Grand Paris (Voir sur ClinicalTrials)
juin 2024
décembre 2031
17 septembre 2025
The RAINBO program is a studies group which proposes personalized treatment of patients
suffering from endometrial cancer according to their molecular profile.
the RAINBO-RED study allows observation or maintenance treatment with targeted therapy
for one year (olaparib). This after standard therapy. The goal is to improve
recurrence-free survival of patients treated with Olaparib.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Cochin | Jerome ALEXANDRE, MD | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Alexandra Leary, MD PhD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Antoine LACASSAGNE - 06189 - Nice - France | Philippe Follana, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier D'Albi - 81000 - Albi - France | Aurelie ASSEMAT, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier de Carcassonne - 11000 - Carcassonne - France | Jean-Luc LABOUREY, MD | Contact (sur clinicalTrials) | |||
| Centre LEON BERARD - 69008 - Lyon - France | Isabelle RAY-COQUARD, MD | Contact (sur clinicalTrials) | |||
| Chu Besancon - 25030 - Besancon - France | Laura MANSI, MD | Contact (sur clinicalTrials) | |||
| CHU De LIMOGES - 87000 - Limoges - France | Elise DELUCHE, MD | Contact (sur clinicalTrials) | |||
| Chu Dijon - 21000 - Dijon - France | Marie CHAIX, MD | Contact (sur clinicalTrials) | |||
| Clinique Sainte Anne - 67000 - Strasbourg - France | YOUCEF TAZI, MD | Contact (sur clinicalTrials) | |||
| Groupe Hospitalier Mutualiste de Grenoble - 38000 - Grenoble - France | Elise BONNET, MD | Contact (sur clinicalTrials) | |||
| Institut Cancerologie de L'Ouest-Angers - 49055 - Angers - France | Paule AUGEREAU, MD | Contact (sur clinicalTrials) | |||
| INSTITUT CANCEROLOGIE DE L'OUEST-St HERBLAIN - 44800 - st - HERBLAIN - France | Jean-Sebastien FRENEL, MD | Contact (sur clinicalTrials) | |||
| Institut Marie-Curie - 75005 - Paris - France | Audrey BELLESOEUR, MD | Contact (sur clinicalTrials) | |||
| Institut Paoli Calmettes - 13009 - Marseille - France | Renaud SABATIER, MD | Contact (sur clinicalTrials) | |||
Critères
Femme
Key inclusion criteria for RAINBO program:
- Histologically confirmed diagnosis of EC (all grades and the following histologic
subtypes : endometrioid, serous, clear cell, de-/undifferentiated carcinomas, and
uterine carcinosarcoma).
- Molecular classification performed following the diagnostic algorithm described in
WHO 2020 (adapted from Vermij et al.)
- TLH-BSO or TAH-BSO 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 PET-CT scan)
- Written informed consent prior to any study specific procedures
- Age >= 18 years
- Patients must have a life expectancy ≥ 16 weeks
- Patients must be accessible for treatment and follow-up
- Written informed consent for one of the RAINBO trials and the overarching research
project according to the local Ethics Committee requirements.
Inclusion criteria specific for p53abn-RED Trial:
- WHO Performance score 0-1
- Histologically confirmed Stage I to III EC with myometrial invasion
- Molecular classification: p53abn EC*
- Body weight > 30 kg
- Adequate systemic organ function: Patients must have normal organ and bone marrow
function measured within 28 days prior to administration of study treatment as
defined below:
- Creatinine clearance (> 50 cc/min): Patients must have creatinine less than 1.5
ULN or calculated creatinine clearance estimated of ≥ 51 mL/min using the
Cockcroft-Gault equation or based on a 24 hour urine test. Estimated creatinine
clearance = (140-age [years]) x weight (kg) (x F) / serum creatinine (mg/dL) x
72
- Adequate bone marrow function : hemoglobin ≥10.0 g/dl with no blood transfusion
in the past 28 days, Absolute neutrophil count (ANC) ≥1.5 x 109/l, platelet
count ≥ 100 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 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
- *Molecular classification must be performed according to the diagnostic algorithm
presented in the WHO 2020 (Vermij et al. 2020). For the p53abn-RED trial this means
that MMR and POLE status must be determined, and must be pMMR and POLE wildtype (or
non-pathogenic) for inclusion. For details on the molecular classification see 7.1:
Diagnostic algorithm for molecular classification.
- Patient should understand, sign, and date the written informed consent form prior to
any protocol-specific procedures performed. Patient should be able and willing to
comply with study visits and procedures as per protocol.
- Patients must be affiliated to a social security system or beneficiary of the same
Exclusion Criteria:
- Other malignancy unless curatively treated with no evidence of disease for ≥5 years
except: adequately treated non-melanoma skin cancer, curatively treated in situ
cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial
carcinoma. Patients with a history of localised triple negative breast cancer may be
eligible, provided they completed their adjuvant chemotherapy more than three years
prior to registration, and that the patient remains free of recurrent or metastatic
disease.
- FIGO Stage IV disease of any histology even if there is no evidence of disease after
surgery
- Prior pelvic irradiation
- Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as
judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic
arrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolyte
disturbances, etc.), or patients with congenital long QT syndrome.
- Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade
2) caused by previous cancer therapy, excluding alopecia.
- Immunocompromised patients, e.g., patients who are known to be serologically
positive for human immunodeficiency virus (HIV).
- Patients considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection. Examples
include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within
3 months) myocardial infarction, uncontrolled major seizure disorder, unstable
spinal cord compression, superior vena cava syndrome, extensive interstitial
bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any
psychiatric disorder that prohibits obtaining informed consent.
- Major surgical procedure (as defined by the Investigator) within 2 weeks prior
randomization and patients must have recovered from any effects of any major
surgery.
- 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.
- Patient with severe hepatic impairment
- 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 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.
- Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin,
clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg.
ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required
washout period prior to starting olaparib is 2 weeks.
- 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, modafinil). The required washout
period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3
weeks for other agents.
- 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.
- Patient under guardianship or deprived of his liberty by a judicial or
administrative decision or incapable of giving its consent
- Patients with a known hypersensitivity to olaparib or any of the excipients of the
product.
- Treatment with an unlicensed or investigational product within 4 weeks of trial
entry.
- Pregnant and breastfeeding patients
- Histologically confirmed diagnosis of EC (all grades and the following histologic
subtypes : endometrioid, serous, clear cell, de-/undifferentiated carcinomas, and
uterine carcinosarcoma).
- Molecular classification performed following the diagnostic algorithm described in
WHO 2020 (adapted from Vermij et al.)
- TLH-BSO or TAH-BSO 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 PET-CT scan)
- Written informed consent prior to any study specific procedures
- Age >= 18 years
- Patients must have a life expectancy ≥ 16 weeks
- Patients must be accessible for treatment and follow-up
- Written informed consent for one of the RAINBO trials and the overarching research
project according to the local Ethics Committee requirements.
Inclusion criteria specific for p53abn-RED Trial:
- WHO Performance score 0-1
- Histologically confirmed Stage I to III EC with myometrial invasion
- Molecular classification: p53abn EC*
- Body weight > 30 kg
- Adequate systemic organ function: Patients must have normal organ and bone marrow
function measured within 28 days prior to administration of study treatment as
defined below:
- Creatinine clearance (> 50 cc/min): Patients must have creatinine less than 1.5
ULN or calculated creatinine clearance estimated of ≥ 51 mL/min using the
Cockcroft-Gault equation or based on a 24 hour urine test. Estimated creatinine
clearance = (140-age [years]) x weight (kg) (x F) / serum creatinine (mg/dL) x
72
- Adequate bone marrow function : hemoglobin ≥10.0 g/dl with no blood transfusion
in the past 28 days, Absolute neutrophil count (ANC) ≥1.5 x 109/l, platelet
count ≥ 100 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 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
- *Molecular classification must be performed according to the diagnostic algorithm
presented in the WHO 2020 (Vermij et al. 2020). For the p53abn-RED trial this means
that MMR and POLE status must be determined, and must be pMMR and POLE wildtype (or
non-pathogenic) for inclusion. For details on the molecular classification see 7.1:
Diagnostic algorithm for molecular classification.
- Patient should understand, sign, and date the written informed consent form prior to
any protocol-specific procedures performed. Patient should be able and willing to
comply with study visits and procedures as per protocol.
- Patients must be affiliated to a social security system or beneficiary of the same
Exclusion Criteria:
- Other malignancy unless curatively treated with no evidence of disease for ≥5 years
except: adequately treated non-melanoma skin cancer, curatively treated in situ
cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial
carcinoma. Patients with a history of localised triple negative breast cancer may be
eligible, provided they completed their adjuvant chemotherapy more than three years
prior to registration, and that the patient remains free of recurrent or metastatic
disease.
- FIGO Stage IV disease of any histology even if there is no evidence of disease after
surgery
- Prior pelvic irradiation
- Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as
judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic
arrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolyte
disturbances, etc.), or patients with congenital long QT syndrome.
- Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade
2) caused by previous cancer therapy, excluding alopecia.
- Immunocompromised patients, e.g., patients who are known to be serologically
positive for human immunodeficiency virus (HIV).
- Patients considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection. Examples
include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within
3 months) myocardial infarction, uncontrolled major seizure disorder, unstable
spinal cord compression, superior vena cava syndrome, extensive interstitial
bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any
psychiatric disorder that prohibits obtaining informed consent.
- Major surgical procedure (as defined by the Investigator) within 2 weeks prior
randomization and patients must have recovered from any effects of any major
surgery.
- 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.
- Patient with severe hepatic impairment
- 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 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.
- Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin,
clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg.
ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required
washout period prior to starting olaparib is 2 weeks.
- 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, modafinil). The required washout
period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3
weeks for other agents.
- 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.
- Patient under guardianship or deprived of his liberty by a judicial or
administrative decision or incapable of giving its consent
- Patients with a known hypersensitivity to olaparib or any of the excipients of the
product.
- Treatment with an unlicensed or investigational product within 4 weeks of trial
entry.
- Pregnant and breastfeeding patients