Clinical Trials Logo

Clinical Trial Summary

The investigators hypothesize that the dual inhibition of mTORC1/mTORC2 by AZD2014 combined with inhibition of aromatase enzyme by anastrozole will act synergistically and may be an interesting therapeutic option for endometrial cancer with a manageable toxicity profile. The investigators proposal is to conduct a multicenter, 2-step, randomized, Phase I/II trial to evaluate the safety and efficacy of a combination treatment associating anastrozole to AZD2014 in advanced endometrial cancer patients. The study is divided in 2 steps : - A safety run-in phase aiming to evaluate the safety of the proposed combination AZD2014 + anastrozole (Arm A) versus anastrozole alone (Arm B). No dose escalation is scheduled (doses are based on maximum tolerated dose (MTD) defined for AZD2014 and the summary of product characteristics (SPC) of anastrozole). However, dose de-escalation for AZD2014 will be applied in case of toxicity. - A two-stage randomized Phase II part aiming to evaluate the clinical benefit of the AZD2014 + anastrozole (Arm A) combination therapy versus anastrozole (Arm B).


Clinical Trial Description

TREATMENT PLAN : Following randomisation patients will receive Arm A : AZD2014 plus anastrozole or Arm B: anastrozole alone AZD2014 will be administered with an intermittent schedule i.e. 125 mg bis in die (BID) intermittent with 2 days on followed by 5 days off per week for a total weekly dose of 500 mg/week (250mg D1 and D2, 5 days off) Anastrozole will be administered at the standard dose defined in the SPC i.e. 1mg/d, per os, continuously. Both treatment will be administered until progressive disease (PD), unacceptable toxicity or willingness to stop. STATISTICS : A total of 72 patients will be randomized in the study. Safety run-in Phase on the first 9 patients randomized - As no dose escalation will be performed, the safety will be evaluated following the treatment and 8-week follow-up of the first 6 patients by the experimental association AZD2014+anastrozole (experimental arm). By similarity to a classic 3+3 design, based on binomial probabilities, there is a 90% probability of observing one or more patients with a toxicity event, if that event occurs in at least 32% of the target population. Assuming a 2:1 randomization ratio, a total of 9 patients (Arm A - Experimental: 6 patients, Arm B - Control: 3 patients) will be enrolled in this safety run-in phase and will be included in the evaluation of Phase II part. Phase II The sample size calculation was based on a Simon optimal two-stage design, with a minimum success (8-week non progression) rate considered of interest p1=60% and an uninteresting rate p0=40%. Assuming a type I error alpha of 0.05 and 80% power, 46 evaluable patients are needed in the experimental arm to reject the null hypothesis H0: p≤p0 versus the alternative hypothesis H1: p ≥ p1 in a unilateral situation (16 patients in Stage I and 30 additional patients in Stage II). With a 2:1 randomization and based on the assumption that 5% of the patients may be non-evaluable, a total of 72 patients will be included in the study : 48 patients in Arm A - experimental and 24 patients in Arm B - control). DATA ENTRY, DATA MANAGEMENT AND STUDY MONITORING All the data concerning the patients will be recorded in the electronic case report form (eCRF) throughout the study. serious adverse event (SAE) reporting will be also paper-based by e-mail and/or Fax. The sponsor will perform the study monitoring and will help the investigators to conduct the study in compliance with the clinical trial protocol, Good Clinical Practices (GCP) and local law requirements. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT02730923
Study type Interventional
Source Centre Leon Berard
Contact
Status Active, not recruiting
Phase Phase 1/Phase 2
Start date April 2016
Completion date December 2024

See also
  Status Clinical Trial Phase
Recruiting NCT05059444 - ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation
Recruiting NCT05036681 - A Phase II Study of Futibatinib and Pembrolizumab in Metastatic Microsatellite Stable Endometrial Carcinoma Phase 2
Completed NCT00756847 - Safety Study of XL147 (SAR245408), in Combination With Paclitaxel and Carboplatin in Adults With Solid Tumors Phase 1
Completed NCT00729586 - Temsirolimus With or Without Megestrol Acetate and Tamoxifen Citrate in Treating Patients With Advanced, Persistent, or Recurrent Endometrial Cancer Phase 2
Completed NCT02983279 - Caloric Restriction Before Surgery in Treating Patients With Endometrial, Prostate, or Breast Cancer N/A
Completed NCT02017353 - Effect of Curcumin Addition to Standard Treatment on Tumour-induced Inflammation in Endometrial Carcinoma Phase 2
Completed NCT00997373 - Letrozole as a Treatment of Endometrial Cancer N/A
Recruiting NCT04851119 - Tegavivint for the Treatment of Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors Phase 1/Phase 2
Recruiting NCT04576104 - Megestrol Acetate Compared With Megestrol Acetate and Metformin to Prevent Endometrial Cancer Phase 2
Not yet recruiting NCT06102252 - Combination Chemotherapy of Paclitaxel and Carboplatin With or Without Anthracycline as an Adjuvant Treatment in Endometrial Carcinoma N/A
Active, not recruiting NCT02598219 - Evaluation of Sentinel Node Policy in Early Stage Endometrial Carcinomas at Intermediate and High Risk of Recurrence. Phase 3
Recruiting NCT04159155 - A Study of Various Treatments in Serous or p53 Abnormal Endometrial Cancer Phase 2/Phase 3
Recruiting NCT05139368 - Hypofractionated Radiotherapy for the Treatment of Cervical or Endometrial Cancer N/A
Recruiting NCT02611024 - Pharmacokinetic Study of Lurbinectedin in Combination With Irinotecan in Patients With Selected Solid Tumors Phase 1/Phase 2
Completed NCT03849469 - A Study of XmAb®22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors Phase 1
Suspended NCT06253494 - Pembrolizumab, Lenvatinib and IL-15 Superagonist N-803 in Combination With HER2 Targeting Autologous Dendritic Cell (AdHER2DC) Vaccine in Participants With Advanced or Metastatic Endometrial Cancer Phase 1/Phase 2
Active, not recruiting NCT03917381 - GEN1046 Safety Trial in Patients With Malignant Solid Tumors Phase 1/Phase 2
Completed NCT03372720 - Fractional CO2 Laser Therapy in Minimizing Genitourinary Syndrome of Menopause in Gynecological Cancer Survivors N/A
Recruiting NCT06413992 - Camrelizumab Plus Fluzoparib for TP-53 Mutated Endometrial Cancer Phase 2
Recruiting NCT05316467 - Weight Management Plus Megestrol Acetate in Early-stage Endometrioid Carcinoma Phase 2/Phase 3