This is a phase IIB, national, randomized, double-blinded, comparative, multi-center study, to assess the efficacy of Olaparib as maintenance after a platinum based chemotherapy in patients with Advanced or metastatic endometrial cancer
Approximately 147 patients will be randomized using an Interactive Voice Response System / Interactive web system (IVR/IWR system) in a 2:1 ratio to the treatments as specified below : * Olaparib tablets per os 300 mg twice daily, * Placebo tablets per os 300 mg twice daily. Before randomization to the study : * Patient should be without evidence of disease (NED), or in clinical complete response or in partial response or stable. * Patient must have completed a minimum of 4 cycles of first line platinum based chemotherapy (recommended chemotherapy is carboplatine AUC 5 plus paclitaxel 175 mg/m2). Patient will be stratified according to : * P53 and MMR Immunohistochemistry, (Y/N) * Response to previous chemotherapy line (Objective response versus Stable) Patients will receive Olaparib/Placebo up to disease progression.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
147
\- Olaparib will be administrated by oral at dose of 300 mg twice daily during the induction period and in maintenance
\- Placebo will be administrated by oral at dose of 300 mg twice daily during the induction period and in maintenance
Efficacy: Progression free survival (PFS1) according to modified Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) of Olaparib maintenance after a platinum based chemotherapy in patients with advanced or metastatic endometrial cancer
Time frame: An average of 36 months
To determine time from randomization until death from any cause
Time frame: To be assessed around 73 months
To determine time from randomization to efficacy by progression free survival
Time frame: To be assessed around 36 months
To determine time from response rate according to IHC P53, MMR, NGS BRCA/HRD, MSI
Time frame: To be assessed around 36 months
To determine the overall response rate ORR
Time frame: To be assessed around 30 months
To determine time from randomization to first and second subsequent therapy (TFST, TSST)
Time frame: To be assessed around 36 months
To determine time from randomization until 2nd disease progression or death (PFS2)
Time frame: To be assessed around 73 months
To assess the safety of Olaparib maintenance compared to placebo - Graded according to CTCAE version 4.03.
Graded according to CTCAE version 4.03. These will be collected by all patients.
Time frame: To be assessed around 36 months
To assess the tolerability of Olaparib maintenance compared to placebo - Graded according to CTCAE version 4.03.
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ICO Paul Papin
Angers, France
Institut du cancer Avignon-Provence
Avignon, France
CHRU Jean Minjoz
Besançon, France
Institut Bergonié
Bordeaux, France
Centre François Baclesse
Caen, France
Centre Jean Perrin
Clermont-Ferrand, France
Centre Hospitalier Intercommunal de Créteil
Créteil, France
Chu Dijon
Dijon, France
Centre Georges François Leclerc
Dijon, France
Institut Daniel Hollard - GHM de Grenoble
Grenoble, France
...and 26 more locations
Graded according to CTCAE (Common Terminology Criteria for Adverse Events) version 4.03. These will be collected by all patients.
Time frame: To be assessed around 36 months
To assess the effects of Olaparib on health-related quality of life (HRQoL) as measure by determining time to deterioration in Quality of life, 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: to be assessed 36 months
To assess the effects of Olaparib 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: to be assessed 36 months
To assess the effects of Olaparib on health-related quality of life (HRQoL) as measure by determining time to deterioration in Quality of life, based on EORTC FA12 (Quality of life Module Measuring Cancer Related Fatigue)
To assess physical, cognitive and emotional aspects of cancer-related fatigue.The higher the score, the better the QOL
Time frame: to be assessed 36 months
To assess the effects of Olaparib on health-related quality of life (HRQoL) as measure by determining time to deterioration in Quality of life, based on Quality of Life Questionnaire EQ5D (consists of a descriptive system and the EQ VAS)
EQ-5D is a standardised measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale. The maximum score of 1 indicates the best health state, by contrast with the scores of individual questions, where higher scores indicate more severe or frequent problems.
Time frame: to be assessed 36 months
To determine efficacy by progression free survival
PFS1 is defined as the time from randomization until the date of the first objective radiological disease progression according to investigator assessment
Time frame: To be assessed around 73 months
To determine response rate according to response to the initial chemotherapy
Time frame: To be assessed around 73 months