Ignite Creation Date:
2024-05-06 @ 8:26 AM
Last Modification Date:
2024-10-26 @ 11:59 AM
Study NCT ID:
NCT02730923
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-02-13
First Post:
2016-03-18
Brief Title:
Hormone Receptor Positive endometrIal Carcinoma Treated by Dual mTORC1mTORC2 Inhibitor and Anastrozole VICTORIA
Sponsor:
Centre Leon Berard
Organization:
Centre Leon Berard
Study Overview
Official Title:
A Multicentric Randomized Non Comparative Open-label Phase III Evaluating AZD2014 Dual Mammalian Target of Rapamycin Complex 12 mTORC1mTORC2 Inhibitor in Combination With Anastrozole Versus Anastrozole Alone in the Treatment of Metastatic Hormone Receptor-positive Endometrial Adenocarcinoma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
VICTORIA
Brief Summary:
The investigators hypothesize that the dual inhibition of mTORC1mTORC2 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 III 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
The investigators proposal is to conduct a multicenter 2-step randomized Phase III 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
Detailed 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 ie 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 mgweek 250mg D1 and D2 5 days off Anastrozole will be administered at the standard dose defined in the SPC ie 1mgd 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 AZD2014anastrozole experimental arm By similarity to a classic 33 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 21 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 p160 and an uninteresting rate p040 Assuming a type I error alpha of 005 and 80 power 46 evaluable patients are needed in the experimental arm to reject the null hypothesis H0 pp0 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 21 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 andor 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
Following randomisation patients will receive Arm A AZD2014 plus anastrozole or Arm B anastrozole alone AZD2014 will be administered with an intermittent schedule ie 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 mgweek 250mg D1 and D2 5 days off Anastrozole will be administered at the standard dose defined in the SPC ie 1mgd 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 AZD2014anastrozole experimental arm By similarity to a classic 33 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 21 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 p160 and an uninteresting rate p040 Assuming a type I error alpha of 005 and 80 power 46 evaluable patients are needed in the experimental arm to reject the null hypothesis H0 pp0 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 21 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 andor 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None