Etude : ENDOLA /

ATTENTION : pour chaque essai clinique, les éléments affichés ci-dessous ne sont pas exhaustifs, et le protocole fourni par le promoteur reste l’unique document à consulter pour mener à bien un essai clinique sur centre. Pour plus d'informations, contactez le référent du territoire concerné.

Acronyme / Nom
Situation thérapeutique
Cadre réglementaire
Présentation de l'étude
Acronyme / Nom : ENDOLA

Situation thérapeutique : Métastatique ou localement avancé

Traitement :

Cadre réglementaire : RIPH2

Dernière MÀJ : 14/10/2019
CIM10 - Localisation(s)
Informations principales
Titre : Essai de phase I/II évaluant la tolérance et l’efficacité de l’association Endoxan métronomique, Metformine et Olaparib dans les cancers de l’endomètre métastatiques ou avancés en rechute 

Spécialité : Seins, organes génitaux de la femme
Localisation : C54 - Tumeur maligne du corps de l'utérus
Informations complémentaires
Schéma : A Phase I/II Trial to Assess the Safety and Efficacy of Metronomic Cyclophosphamide, Metformin and Olaparib in Recurrent Advanced/Metastatic Endometrial Cancer Patients

1 arm:
- Experimental: Olaparib, metformin and metronomic cyclophosphamide
-> Phase 1: Dose escalation scheme: a continual reassessment method (CRM) will be used to guide inclusion of patients in drug dose levels pre-specified based on observations of dose-limiting toxicity.
-> Phase 2 (expansion of cohort): once RP2D will be determined, additional patients will be enrolled, in order to obtain preliminary data about efficacy in a 2 stage Simon's design.

Phase : I/II

Stade : Localement avancé à Métastatique

2, 3, 4
Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Woman older than 18 years and younger than 81 year old
- Patients with histologically and/or cytologically documented endometrial carcinoma (type I or type II), recurrent after platinum-based chemotherapy.
- Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Archival tumor tissue available, or tumor lesion biopsy feasible
- There is no limitation to prior number of therapies
- Patients who have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Patients with adequate bone marrow function
-> Absolute granulocyte count ≥ 1.5 x 10 9 /L
-> Platelet count ≥ 100 x 10 9 /L
-> Haemoglobin ≥ 9 g/dL
- Patients with adequate renal function :
* Calculated creatinine clearance, according to the Modification of the Diet in Renal Disease (MDRD) formula >= 60 ml/min
- Patients with adequate hepatic function
*Serum total bilirubin < 1.25 x upper normal limit (UNL) and aspartate aminotransferase (AST)/Alanine Amino transferase (ALT) ≤ 2.5 X UNL (≤ 5 X UNL for patients with liver metastases)
- Patients must have a life expectancy ≥ 16 weeks
- Female patients who are of childbearing potential: evidence of non-childbearing status, practicing a medically acceptable method of birth control during the study and 12 months after the end of treatment
- Patients who gave its written informed consent to participate to the study
- Patients affiliated to a social insurance regime

Critères de non-inclusion : - Illness, incompatible with metformin treatment, in particular those associated with a risk of hypoperfusion or hypoxia (not limited to): acute or chronic renal failure (creatinine clearance < 60 ml/min, according to the MDRD formula); lactic ketoacidosis; septic shock; congestive heart failure; respiratory distress; liver failure; chronic alcoholism; uncontrolled seizures; age > 80 years; allergy/hypersensitivity to metformin.
- Previous treatment with cyclophosphamide; or allergy/hypersensitivity to cyclophosphamide.
- Any previous treatment with a poly-adenosine diphosphate ribose (ADP) ribose polymerase (PARP) inhibitor, including olaparib.
- Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years.
- Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment. The patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment with study drug.
- Concomitant use of known CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin boceprevir, telaprevir and nelfinavir and inducers such phenobarbital, phenytoin, carbamazepine, rifampicin.
- Persistent toxicities (>=CTCAE grade 2) with the exception of alopecia, caused by previous cancer therapy.
- Treatment with other investigational agents.
- Bowel occlusive syndrome or other gastro-intestinal disorder that does not allow oral medication such as malabsorption.
- Female patients who are pregnant or lactating, Active infection to HIV, hepatitis B or C, or have other forms of hepatitis or cirrhosis.
- Symptomatic uncontrolled brain metastases. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 28 days prior to treatment.
- Major surgery within 14 days of starting study treatment
- Patients must have recovered from any effects of any major surgery.
- Resting ECG with corrected QT interval (QTc) > 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
- Concomitant treatment with vitamin K antagonists
- Patients under guardianship.
Informations relatives au promoteur
Promoteur :
Type de sponsor : Institutionnel
3, avenue du Général Harris
14000 CAEN

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Centre François BACLESSE - 3 avenue du Général Harris - 14000 CAEN
Apicrypt :

Investigateur :
Florence JOLY


Statut de l'essai : CLOS

MAJ : 14/10/2019