Phase 3, randomized, multicentre study to evaluate the efficacy and safety of dostarlimab versus carboplatin-paclitaxel in patients with MMR deficient relapse or advanced endometrial cancer.
Phase III, randomized, open label, multi-centre study. Randomization on a 1:1 ratio, stratification performed according to: * Prior adjuvant chemotherapy (yes or no) * Prior pelvic radiotherapy (yes or no) * Disease status: newly diagnosed advanced / metastatic disease versus relapse
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
260
Chemotherapy will be administered by intravenous infusion. Carboplatin AUC 5-6 + Pacltaxel 175 mg/m² every 3 weeks. Total duration of treatment: 6 cycles
Dostarlimab will be administered through a 30-minute infusion at a dose of 500 mg Q3W from Cycle 1 through Cycle 4 and at a dose of 1,000 mg Q6W thereafter, beginning at Cycle 5 Day 1 up to a maximum of 2 years.
Progression Free Survival (PFS)
Defined as the time from the date of randomization until objective tumor progression based on RECIST 1.1, by BICR (Blinded Independent Central Review), or death due to any cause, whichever occurs first. Patients alive and free of progression will be censored at the last disease assessment date.
Time frame: from the date of randomization until objective tumor progression based on RECIST 1.1, or death due to any cause, whichever occurs first assessed up to 5 years.
Overall Survival (OS) (key secondary endpoint)
Measured as the time from the date of randomization to the date of death due to any cause. Patients alive at the cut-off date will be censored at the last date they are known to be alive.
Time frame: from the date of randomization until death due to any cause, assessed up to 5 years
Progression Free Survival 2 (PFS2)
Defined by the time from initial randomization to the second objective disease progression (ie, after the first subsequent therapy) as assessed by the investigator or death due to any cause, whoever occurs first. Patients alive and free of second progression (including patients without any progression), will be censored at the last disease assessment date.
Time frame: from the date of randomization until second objective tumor progression based on RECIST 1.1, or death due to any cause, whichever occurs first assessed up to 5 years
Quality Of Life evaluation based on Quality of Life Questionnaire EQ5D5L (The 5-level EQ-5D version)
The EQ-5D-5L essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems
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Canberra Hospital
Garran, Australia
Calvary Mater Newcastle
Waratah, Australia
Princess Margaret Cancer Centre
Toronto, Canada
CHU d'Amiens - Hôpital Sud
Amiens, France
Clinique de l'Europe
Amiens, France
ICO Paul Papin
Angers, France
Centre Hospitalier d'Auxerre
Auxerre, France
Institut Sainte Catherine
Avignon, France
CH Simone Veil de Beauvais
Beauvais, France
CHRU Jean Minjoz
Besançon, France
...and 90 more locations
Time frame: through study completion, an average of 5 years
To assess the effects of Dostarlimab on Health related quality of Life (QoL) based on EORTC QLQ C30 (Quality of Life questionnaire-core 30)
Health related quality of life of the patient. For all scales a high score is equivalent to worse or more problems. Range is the difference between the maximum and minimum possible value of the raw score. All items are scored from1 to 4, giving a range=3. For each scale, calculate the raw score by the addition of item responses divided by the number of items. Then a linear transformation is used to standardise the raw score, so that scores range from 0 to 100. Score= (raw score-1)/rangex100
Time frame: Defined as the Global Health Status score from the EORTC QLQ C30 at 18 weeks, assessed up to 5 years
To assess the quantity of peripheral neuropathy event induced by chemotherapy based on EORTC QLQ-CIPN 20 (Quality of Life questionnaire-Chemotherapy induced peripheral neuropathy 20)
Chemotherapy induced peripheral neuropathy assessed by QLQ-CIPN20 at 18 weeks for each problems or symptoms there are a scales with a high score which is equivalent to worse or more. All items are scored from1 to 4, giving a range=3. 1 = Not at all and 4 = Very much. For each scale, calculate the raw score by the addition of item responses divided by the number of items.
Time frame: Defined as the Global Health Status score from the EORTC QLQ-CIP20 at 18 weeks, assessed up to 5 years
To assess the effects of treatment on health-related quality of life (HRQoL) as measure by determining time to deterioration in Quality of life, based EORTC QLQ-EN24 (Quality of Life Questionnaire - Endometrial Cancer Module)
To assess disease and treatment specific aspects of the quality of life of patients with endometrial cancer. A high score for the functional scales represents a high level of functioning, while a high score for the symptom scales represents a high level of symptoms or problems. Symptoms related to sexual/vaginal problems (EMSXV including item 51-53) are optional.
Time frame: Defined as the Global Health Status score from the EORTC QLQ-EN24 at 18 weeks, assessed up to 5 years
To assess the status of health for patients with endometrial cancer based on EUROQOL EQ-5D (Descriptive system)
Deterioration and impact on patients' life of endometrial cancer assessed by the questionnaire EUROQOL EQ-5D
Time frame: Defined as the Global Health Status score from the EUROQOL EQ-5D at 18 weeks, assessed up to 5 years
Best Objective Response Rate (ORR)
Defined as the proportion of patients with confirmed complete or partial response as per RECIST 1.1
Time frame: from the date of randomization until best objective response based on RECIST 1.1, assessed up to 5 years
Disease Control Rate (DCR)
Defined as the proportion of participants who have achieved confirmed CR or PR or have demonstrated SD for at least 24 weeks; per RECIST 1.1.
Time frame: from the date of randomization until response or stable disease per RECIST 1.1, assessed up to 5 years
Duration of Response Rate (DoR)
Measured from the time of initial response until documented tumor progression.
Time frame: from the time of initial response until documented tumor progression ,assessed up to 5 years
Safety and number of adverse events
Measured from the time of initial response until documented tumor progression.
Time frame: From date of randomization until end of study, assessed up to 6 years
Tolerability to the treatment
Assessed by CTCAE v5.0 (by investigators) Assessed by NCI PRO-CTCAE (by patients)
Time frame: From date of randomization until end of study, assessed up to 6 years
Time to first and second Subsequent Treatment
Defined as the time from the date of randomization to date of respectively the first and second subsequent anticancer therapy or death.
Time frame: from the date of randomization to date of event, assessed up to an average of 5 years
To determine the immunogenicity of dostarlimab
Incidence of ADA against dostarlimab
Time frame: from randomisation to 12 weeks after end of treatment, assessed at study end