November 22, 2021
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January 21, 2022
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February 29, 2024
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April 15, 2022
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April 2026 (Final data collection date for primary outcome measure)
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Progression Free Survival (PFS) [ 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. ] 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.
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Progression Free Survival (PFS) [ 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. ]
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- Overall Survival (OS) (key secondary endpoint) [ Time Frame: from the date of randomization until death due to any cause, assessed up to 5 years ]
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.
- Progression Free Survival 2 (PFS2) [ 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 ]
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.
- Quality Of Life evaluation based on Quality of Life Questionnaire EQ5D5L (The 5-level EQ-5D version) [ Time Frame: through study completion, an average of 5 years ]
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
- To assess the effects of Dostarlimab on Health related quality of Life (QoL) based on EORTC QLQ C30 (Quality of Life questionnaire-core 30) [ Time Frame: Defined as the Global Health Status score from the EORTC QLQ C30 at 18 weeks, assessed up to 5 years ]
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
- 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) [ Time Frame: Defined as the Global Health Status score from the EORTC QLQ-CIP20 at 18 weeks, assessed up to 5 years ]
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.
- 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) [ Time Frame: Defined as the Global Health Status score from the EORTC QLQ-EN24 at 18 weeks, assessed up to 5 years ]
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.
- To assess the status of health for patients with endometrial cancer based on EUROQOL EQ-5D (Descriptive system) [ Time Frame: Defined as the Global Health Status score from the EUROQOL EQ-5D at 18 weeks, assessed up to 5 years ]
Deterioration and impact on patients' life of endometrial cancer assessed by the questionnaire EUROQOL EQ-5D
- Best Objective Response Rate (ORR) [ Time Frame: from the date of randomization until best objective response based on RECIST 1.1, assessed up to 5 years ]
Defined as the proportion of patients with confirmed complete or partial response as per RECIST 1.1
- Disease Control Rate (DCR) [ Time Frame: from the date of randomization until response or stable disease per RECIST 1.1, assessed up to 5 years ]
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.
- Duration of Response Rate (DoR) [ Time Frame: from the time of initial response until documented tumor progression ,assessed up to 5 years ]
Measured from the time of initial response until documented tumor progression.
- Safety and number of adverse events [ Time Frame: From date of randomization until end of study, assessed up to 6 years ]
Measured from the time of initial response until documented tumor progression.
- Tolerability to the treatment [ Time Frame: From date of randomization until end of study, assessed up to 6 years ]
Assessed by CTCAE v5.0 (by investigators) Assessed by NCI PRO-CTCAE (by patients)
- Time to first and second Subsequent Treatment [ Time Frame: from the date of randomization to date of event, assessed up to an average of 5 years ]
Defined as the time from the date of randomization to date of respectively the first and second subsequent anticancer therapy or death.
- To determine the immunogenicity of dostarlimab [ Time Frame: from randomisation to 12 weeks after end of treatment, assessed at study end ]
Incidence of ADA against dostarlimab
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- Quality Of Life evaluation based on EORTC QLQ-C30 (Quality Of Life Questionnaire-core 30) [ Time Frame: through study completion, an average of 5 years ]
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
- Quality Of Life evaluation based EORTC QLQ-EN24 (Quality of Life Questionnaire - Endometrial Cancer Module) [ Time Frame: through study completion, an average of 5 years ]
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.
- Quality Of Life evaluation based on Quality of Life Questionnaire EQ5D5L (The 5-level EQ-5D version) [ Time Frame: through study completion, an average of 5 years ]
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
- Quality Of Life evaluation based on Quality of Life Questionnaire I-ADL Scale (Index of Independence in Activities of Daily Living) [ Time Frame: through study completion, an average of 5 years ]
Activities of daily living are activities related to personal care. The IADLs denote what an individual normally do in his/her daily living. The person answer to several item and all are scored from 0 (dependence) to 1 (Independence).
- Quality Of Life evaluation based on Quality of Life Questionnaire CIPN20 (Chemotherapy-induced peripheral neuropathy) [ Time Frame: through study completion, an average of 5 years ]
CIPN-20 is a patient self-report questionnaire of 20 items. Should provide valuable information on CIPN related symptoms and functional limitations of patients exposed to potentially neurotoxic chemotherapeutic and/or neuroprotective agents. All items are scored from 1 to 4. The raw score is calculated by addition of item responses divided by the number of items. A high score is equivalent to worse.
- Objective Response Rate [ Time Frame: through study completion, an average of 5 years ]
proportion of patients with tumor size reduction of a predefined amount
- Duration of Response Rate [ Time Frame: from the time of initial response until documented tumor progression up to 5 years ]
- Overall Survival [ Time Frame: from the date of randomization until death due to any cause up to 5 years ]
- Safety evaluation [ Time Frame: through study completion, an average of 5 years ]
Graded according to CTCAE (Common Terminology Criteria for Adverse Events) version 5.0. These will be collected by all patients.
- Time to first and second subsequent treatment [ Time Frame: time from the date of randomization to date of the first and second subsequent anticancer therapy or death up to 5 years ]
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Not Provided
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Not Provided
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Endometrial Cancer Patientes MMR Deficient Comparing Chemotherapy vs Dostarlimab in First Line
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Randomized Phase III Trial in MMR Deficient Endometrial Cancer Patients Comparing Chemotherapy Alone Versus Dostarlimab in First Line Advanced/Metastatic Setting
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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.
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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
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Interventional
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Phase 3
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Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment
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Endometrial Cancer
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- Drug: Carboplatin-Paclitaxel
Chemotherapy will be administered by intravenous infusion. Carboplatin AUC 5-6 + Pacltaxel 175 mg/m² every 3 weeks. Total duration of treatment: 6 cycles
- Drug: Dostarlimab
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.
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Not Provided
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Recruiting
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260
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142
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October 2029
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April 2026 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
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Patients must fulfil all the following criteria:
- Female patient is at least 18 years of age,
- Patient has signed the Informed Consent (ICF) and is able to comply with protocol requirements.
- Patient with histologically proven endometrial adenocarcinoma with recurrent or advanced disease.
- Patient with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
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Patient must have primary Stage IIIA to C2 or Stage IV disease or first recurrent endometrial cancer (see International Federation of Gynecology and Obstetrics staging FIGO Staging 18.1) without curative treatment by radiation therapy or surgery alone or in combination, and meet at least one of the following situations:
- Patient has patient has primary Stage IIIA-IIIC1 with no amenable curative intent surgery or radiation.
- Patient has first recurrent disease and is chemotherapy naïve for this 1st recurrence or metastatic setting.
- Patient has recurrent disease and is chemotherapy naïve for recurrence or advanced /metastatic setting.
- Patient may have received prior irradiation for advanced endometrial cancer with or without radio-sensitizing chemotherapy if > 3 weeks before the start of the study
- Patient with evaluable disease (measurable and not measurable disease) according to RECIST 1.1
- Patient may have received prior neo-adjuvant/adjuvant systemic chemotherapy for the primary cancer and had a recurrence ≥ 6 months after completing treatment (first recurrence only).
- All histologic subtypes of endometrial adenocarcinoma could be included if MMRd/MSI-H
- MMRd/MSI-H tumor (first diagnosed by routine local IHC performed either on primitive tumour tissue or on relapse/metastatic tumour sample) is mandatory for inclusion. A central confirmation will be done before inclusion; in case of ambiguous result of central IHC (lack of positive internal control, heterogeneous loss of MMR protein expression), MSI-H status will be assessed by PCR/NGS
- Availability of 1 block for MMR/MSI status centralized confirmation for IHC or PCR/ NGS, and additional block(s) for Translational Research
- . Patient could have been previously treated with hormone therapy, for the metastatic/advanced disease 12) Patient may have received pelvic and lombo-aortic external beam +/- vaginal brachytherapy
13. Patient has adequate organ function, defined as follows:
a) Absolute neutrophil count ≥ 1,500 cells/μL b) Platelets ≥ 100,000 cells/μL c) Haemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L d) Serum creatinine ≤ 1.5× upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault equation for patients with creatinine levels > 1.5× institutional ULN e) Total bilirubin ≤ 1.5× ULN (≤ 2.0 x ULN in patients with known Gilbert's syndrome) or direct bilirubin ≤ 1× ULN f) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5× ULN unless liver metastases are present, in which case they must be ≤ 5× ULN g) International normalized ratio or prothrombin time (PT) ≤1.5× ULN and activated partial thromboplastin time ≤1.5× ULN. Patients receiving anticoagulant therapy must have a PT or partial thromboplastin within the therapeutic range of intended use of anticoagulants.
14. Patient must have a negative serum pregnancy test within 72 hours of the first dose of study medication, unless they are of nonchildbearing potential. Nonchildbearing potential is defined as follows:
- Patient is ≥ 45 years of age and has not had menses for > 1 year.
- A follicle-stimulating hormone value in the postmenopausal range upon screening evaluation if amenorrhoeic for < 2 years without a hysterectomy and oophorectomy.
- Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation:
- Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound, MRI, or CT scan.
- Tubal ligation must be confirmed with medical records of the actual procedure; otherwise, the patient must fulfil the criteria in Inclusion Criterion 14.
- Information must be captured appropriately within the site's source documents. 15. Patient of childbearing potential must agree to use a highly effective method of contraception (section 18.9) with their partners starting from time of consent through 150 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient (Information must be captured appropriately within the site's source documents).
Exclusion Criteria:
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Sexes Eligible for Study: |
Female |
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18 Years and older (Adult, Older Adult)
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No
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Australia, France, Singapore
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NCT05201547
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GINECO-EN105b
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
No |
Studies a U.S. FDA-regulated Device Product: |
No |
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Not Provided
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ARCAGY/ GINECO GROUP
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Same as current
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ARCAGY/ GINECO GROUP
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Same as current
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GlaxoSmithKline
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Principal Investigator: |
Florence JOLY, Pr |
Centre François Baclesse |
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ARCAGY/ GINECO GROUP
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December 2023
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