Patients with epithelial ovarian cancer (including patients with primary peritoneal and / or fallopian tube adenocarcinoma) who have first or second late relapse (platinum-free interval > 6 months) MedDRA version: 20.0 Level: PT Classification code 10016180 Term: Fallopian tube cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version:
Conditions
Interventions
Product Name: Atezolizumab
Product Code: MPDL3280A
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Atezolizumab
Current
Sponsors
ARCAGY-GINECO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: I-1. Female Patients must be =18 years of age. I-2. Signed informed consent and ability to comply with treatment and follow-up. I-3. Patients with histologically confirmed progressive non-mucinous epithelial ovarian cancer, primary peritoneal adenocarcinoma and / or fallopian-tube adenocarcinoma. I-4. Patients with PD-L1 status determined for stratification on mandatory de novo biopsy sent to central laboratory as a formalin-fixed, paraffin-embedded (FFPE) sample: Cell pellet from pleural effusion, or ascites or lavage are not acceptable.; For core needle biopsy specimens, at least three cores should be obtained. Biopsies must be obtained in a manner that minimizes risks for the patient and maximizes the chance to get tumor tissue. In case the core biopsies do not contain significant tumor tissue, patient eligibility should be discussed with the sponsor I-5. Patients whose disease has relapsed more than 6 months from the last dose of platinum before randomization: a) Criterion for relapse can be according to RECIST v1.1, CA125 (GCIG) or clinical symptoms; b) The interval between last dose of platinum and entry in the study should be free of new anti-cancer treatment, with the exception of a maintenance therapy which is allowed up to 21 days before study entry. I-6. Patients with one or 2 prior lines of chemotherapy. The last line of chemotherapy should have included platinum. I-7.Availability at the study site of representative FFPE archival tumor sample from surgery during front-line therapy, at best before chemotherapy. I-8. Patients must have normal organ and bone marrow function: a) Haemoglobin = 10.0 g/dL. ; b) Absolute neutrophil count (ANC) = 1.5 x 109/L; c) Platelet count = 100 x 109/L; d) Total bilirubin = 1.5 x institutional upper limit of normal (ULN); e) Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT) and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) = 2.5 x ULN, unless liver metastases are present in which case they must be = 5 x ULN; f) Serum creatinine = 1.5 x institutional ULN; g) Patients not receiving anticoagulant medication who have an International Normalized Ratio (INR) =1.5 and an Activated ProThrombin Time (aPTT) =1.5 x ULN. The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or APTT is within therapeutic limits (according to site medical standard) and if the patient is on a stable dose of anticoagulants for at least two weeks at the time of randomization; h) Urine dipstick for proteinuria =65 years) yes F.1.3.1 Number of subjects for this age range 162
Exclusion criteria
Exclusion criteria: E-1.Non-epithelial ovarian tumor, the fallopian tube or the peritoneum (i.e. germ cell tumors). E-2.Ovarian tumors of low malignant potential (borderline tumors). e-3.Synchronous primary endometrial cancer (Ca) unless a) Stage 325 mg/day. E-18.Prior history of hypertensive crisis (CTC-AE grade 4) or hypertensive encephalopathy. E-19.Inadequately controlled HTN. E-20.Clinically significant (e.g. active) cardiovascular disease. E-21.Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome. E-22.Left ventricular ejection fraction by MUGA/ECHO below the institutional lower limit of normal (applicable for patients intended to be treated with PLD). E-23.Previous Cerebro-Vascular Accident, Transient Ischemic Attack or Sub-Arachnoids Hemorrhage within 6m prior to
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Determine the efficacy of atezolizumab vs placebo on: • Time from randomization to second subsequent therapy or death • Health-related Quality of Life and patient reported outcomes as measured by EORTC QLQ-C30 and OV28 • Long term survival using the cure rate modelling • Overall survival • Objective Response Rate as assessed by RECIST v1.1 and irRECIST • PFS1 as assessed per irRECIST • Characterization of CA-125 tumor marker levels and their relation to tumor response and PFS1 as measured by RECISTv 1.1 and irRECIST • Time from randomization to first subsequent therapy or death • Time from randomization to second progression • in the PD-L1-ve and PD-L1 +ve subgroups To assess the safety and tolerability of atezolizumab compared to placebo To evaluate the impact of treatment and disease on resource use as measured by different criteria including EuroQoL 5 Dimension questionnaire ; Primary end point(s): Progression free-survival (PFS1). PFS1 is defined as the time from randomization until the date of the first objective radiological disease progression according to investigator assessment of RECIST version 1.1 or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomized study treatment or receives another anti-cancer therapy prior to progression ; Timepoint(s) of evaluation of this end point: 278 events observed for the primary analysis. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable RECIST assessment. ;Main Objective: The primary efficacy outcome measure is investigator determined progres | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary supportive objectives To determine the efficacy of atezolizumab compared to placebo on: • Time from randomization to second subsequent therapy or death (TSST) • Health-related Quality of Life (HRQoL) and patient reported outcomes (PROs) as measured by EORTC QLQ-C30 and OV28 •Long term survival using the cure rate modelling •Overall survival (OS) Others secondary objectives To determine the efficacy of atezolizumab compared to placebo on: • Objective Response Rate (ORR) as assessed by RECIST v1.1 and irRECIST • PFS1 as assessed per irRECIST • Characterization of CA-125 tumor marker levels and their relation to tumor response and PFS1 as measured by RECISTv 1.1 and irRECIST • Time from randomization to first subsequent therapy or death (TFST) • Time from randomization to second progression (PFS2) Others secondary objectives To determine the efficacy of atezolizumab compared to placebo in the PD-L1-ve and PD-L1 +ve subgroups To assess the safety and tolerability of atezolizumab compared to placebo To evaluate the impact of treatment and disease on resource use as measured by different criteria including EuroQoL 5 Dimension (EQ-5D) questionnaire Exploratory objectives 1. To explore pre-planned subgroups analyses of efficacy (PFS) based on relevant potential prognostic factors, including stratification factors, as well as on the performance or not of secondary cytoreductive surgery. 2. To evaluate the relationship between the expression of PD-L1, tumor mutational load and intraepithelial TILs with ORR and PFS. 3. To evaluate the relationship between the expression of PD-L1, tumor mutational load and intraepithelial | — |
Countries
Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Israel, Norway, Spain, Sweden
Contacts
Public ContactFederico Nepote
MFAR Clinical Research
Outcome results
None listed