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ATALANTE: Atezolizumab vs Placebo Phase III Study in Late Relapse Ovarian Cancer Treated With Chemotherapy+Bevacizumab (ATALANTE)

Primary Purpose

Ovarian Cancer

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
atezolizumab + avastin + platinum-based chemotherapy
placebo + avastin + platinum-based chemotherapy
Sponsored by
ARCAGY/ GINECO GROUP
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring PD-L1, Atezolizumab, Randomized, double blinded, first or second late relapse, progressive non-mucinous epithelial ovarian cancer, primary peritoneal adenocarcinoma and / or fallopian-tube adenocarcinoma, progression-free survival

Eligibility Criteria

18 Years - 95 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Female Patients must be ≥18 years of age.
  2. Signed informed consent and ability to comply with treatment and follow-up.
  3. Patients with histologically confirmed progressive non-mucinous epithelial ovarian cancer, primary peritoneal adenocarcinoma and / or fallopian-tube adenocarcinoma
  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. If the location of the tumor renders tumor biopsy medically unsafe or not feasible, patient eligibility should be discussed with the sponsor.
  5. Patients whose disease has relapsed more than 6 months from the last dose of platinum before randomization:

    1. criterion for relapse can be according to RECIST v1.1, CA-125 (GCIG) or clinical symptoms
    2. 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.
  6. Patients with one or 2 prior lines of chemotherapy. The last line of chemotherapy should have included platinum.
  7. Availability at the study site of representative FFPE tumor sample from surgery during front line therapy, at best before chemotherapy
  8. Patients must have normal organ and bone marrow function :

    1. Haemoglobin ≥ 10.0 g/dL.
    2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
    3. Platelet count ≥ 100 x 109/L.
    4. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
    5. 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.
    6. Serum creatinine ≤ 1.5 x institutional ULN,
    7. 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.
    8. Urine dipstick for proteinuria < 2+. If urine dipstick is ≥2+, 24-hours urine must demonstrate ≤1 g of protein in 24 hours.
    9. Normal blood pressure or adequately treated and controlled hypertension (systolic BP ≤ 140 mmHg and/or diastolic BP ≤ 90 mmHg).
  9. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

For France only: In France, a subject will be eligible for randomization in this study only if either affiliated to, or a beneficiary of, a social security category

Exclusion Criteria:

  1. Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors).
  2. Ovarian tumors of low malignant potential (e.g. borderline tumors)
  3. Patients with synchronous primary endometrial cancer unless both of the following criteria are met:

    1. stage < II,
    2. Less than 60 years old at the time of diagnosis of endometrial cancer with stage IA or IB grade 1 or 2, or stage IA grade 3 endometrioid adenocarcinoma OR ≥ 60 years old at the time of diagnosis of endometrial cancer with stage IA grade 1or 2 endometrioid adenocarcinoma.
    3. Patients with serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium are not eligible.
  4. Other malignancy within the last 5 years except cervix or breast in situ carcinoma, breast cancer ≥ 3 years free of disease and treatment, type I stage I endometrial cancer).
  5. Patients receiving radiotherapy within 6 weeks prior to study treatment.
  6. Major surgery within 4 weeks of starting study treatment or patients who have not completely recovered from the effects of any major surgery. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1, Cycle 1
  7. Previous allogeneic bone marrow transplant or previous solid organ transplantation.
  8. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy is permitted).
  9. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD1, or anti-PDL1 therapeutic antibodies or anti-CTLA 4.
  10. Treatment with systemic immunostimulatory agents (including but not limited to interferon-alpha (IFN-α) and interleukin-2 (IL-2) within 4 weeks or five half-lives of the drug (whichever is shorter) prior to Cycle 1, Day 1
  11. Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial

    1. The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.
    2. Prophylactic anti-emetic corticosteroids will be avoided if possible in patients treated with pegylated liposomal doxorubicin-carboplatin or gemcitabine-carboplatin regimen. The use of corticosteroids is allowed as premedication for paclitaxel-based regimen and/or premedication in case of carboplatin hypersensitivity.
  12. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Are eligible patients with:

    1. a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone
    2. controlled Type 1 diabetes mellitus on a stable insulin regimen
  13. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis. Radiation pneumonitis in the radiation field (fibrosis) detected on screening chest CT scan is permitted
  14. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV). Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C.

    Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.

  15. Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
  16. Administration of a live, attenuated vaccine within 4 weeks prior to Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study. Influenza vaccination should be given during influenza season only (example approximately October to March in the Northern Hemisphere). Patients must not receive live, attenuated influenza
  17. Current or recent (within 10 days prior to randomization) chronic use of aspirin > 325 mg/day.
  18. Prior history of hypertensive crisis (CTC-AE grade 4) or hypertensive encephalopathy.
  19. Inadequately controlled HTN (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
  20. Clinically significant (e.g. active) cardiovascular disease, including:

    1. Myocardial infarction or unstable angina within ≤ 6 months of randomization,
    2. New York Heart Association (NYHA) ≥ grade 2 congestive heart failure (CHF),
    3. Poorly controlled cardiac arrhythmia despite medication (patients with rate controlled atrial fibrillation are eligible),
    4. Peripheral vascular disease grade ≥ 3 (e.g. symptomatic and interfering with activities of daily living [ADL] requiring repair or revision)
  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.
  22. Left ventricular ejection fraction defined by MUGA/ECHO below the institutional lower limit of normal (only applicable for patients intended to be treated with pegylated liposomal doxorubicin).
  23. Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub-Arachnoids Hemorrhage (SAH) within 6 months prior to randomization.
  24. History or evidence of hemorrhagic disorders within 6 months prior to randomization.
  25. Evidence of bleeding diathesis or significant coagulopathy (in the absence of coagulation).
  26. History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of suspected spinal cord compression.
  27. History or evidence upon neurological examination of central nervous system (CNS) disease, unless adequately treated with standard medical therapy (e.g. uncontrolled seizures).
  28. Significant traumatic injury during 4 weeks prior to randomization.
  29. Non-healing wound, active ulcer or bone fracture. Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require 3 weekly wound examinations.
  30. History of VEGF therapy related abdominal fistula or gastrointestinal perforation.
  31. Current, clinically relevant bowel obstruction, including sub-occlusive disease, related to underlying disease.
  32. Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
  33. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment related complications.
  34. Women of childbearing potential (<2 years after last menstruation and not surgically sterile) not willing to use highly-effective means of contraception (Appendix 1) during the study and for 6 months after the last dose of study medication
  35. Pregnant or lactating women.
  36. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
  37. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation.
  38. Known hypersensitivity reaction or allergy to drugs chemically related to bevacizumab, carboplatin, gemcitabine, paclitaxel, pegylated liposomal doxorubicin, or their excipients that contraindicates the subject's participation

Sites / Locations

  • Krankenhaus der Barmherzigen Brüder Graz
  • Medical University of Graz
  • Medical University of Innsbruck
  • Medical University of Vienna
  • UZ Gent
  • Uz Leuven
  • General University Hospital in Prague
  • ICO Paul Papin
  • Sainte-Catherine Institut du Cancer Avignon-Provence
  • CHRU Jean Minjoz
  • Clinique Tivoli
  • Institut Bergonié
  • Centre François Baclesse
  • Centre Jean Perrin
  • Groupe Hospitalier Mutualiste de Grenoble
  • Hôpital Michallon - Centre Hospitalier Universitaire de Grenoble
  • Centre Hospitalier Départemental Les Oudairies
  • Centre Oscar Lambret
  • Centre Léon Bérard
  • Institut Paoli Calmettes
  • Hôpital de Mont-de-Marsan
  • ICM Val d'Aurelle
  • Centre Azuréen de Cancérologie
  • ORACLE - Centre d'Oncologie de Gentilly
  • Hôpital Privé du Confluent, S.A.S.
  • Centre Antoine Lacassagne
  • CHU Nîmes - Institut de Cancérologie du Gard
  • Centre Hospitalier Régional d'Orléans
  • Groupe Hospitalier Diaconesses-Croix Saint Simon
  • Groupe Hospitalier Saint-Joseph
  • Hôpital Cochin
  • Hôpital Européen Georges Pompidou
  • Hôpital Tenon
  • Institut Curie - Hopital Claudius Régaud
  • Centre Hospitalier Lyon Sud
  • Centre CARIO - HPCA
  • Hôpital de la Milétrie - Centre Hospitalier Universitaire de Poitiers - Pôle Régional de Cancérologie
  • Centre Eugène Marquis
  • Hôpital René Huguenin, Institut Curie
  • ICO Centre René Gauducheau
  • Centre Paul Strauss
  • Institut de Cancérologie Strasbourg Europe (ICANS)
  • Clinique Pasteur
  • Institut Claudius Regaud
  • ICL Institut de Cancérologie de Lorraine
  • Gustave Roussy
  • Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin
  • Universitätsklinikum Carl Gustav Carus
  • Universitatsklinikum Dusseldorf
  • Kliniken Essen Mitte, Evang. Huyssens-Stiftung
  • Universitätsklinikum Essen
  • Universitätsklinikum Hamburg-Eppendorf
  • Medizinische Hochschule Hannover
  • Universitätsklinikum Jena
  • Städtisches Klinikum Karlsruhe
  • Klinikum der Universität München - LMU, Campus Großhadern
  • Klinikum rechts der Isar, Technischen Universität München
  • Sana Klinikum Offenbach
  • Studienzentrum Onkologie Ravensburg
  • Universitatsklinikum Tübingen
  • Universitätsklinikum Ulm
  • Klinikum Worms
  • Sharre Zedek Medical Centre
  • Hospital Universitari Vall d'Hebron
  • Hospital Clínic Barcelona
  • Hospital San Pedro de Alcántara
  • Hospital Universitari de Girona ICO Girona (Dr. Josep Trueta)
  • Hospital Universitario Clínico San Carlos
  • Hospital Universitario La Paz
  • Hospital Universitario HM Sanchinarro
  • Hospital Central Universitario Virgen de la Arrixaca
  • Hospital Universitario Son Espases
  • Hospital Universitario Donostia
  • Hospital Universitario Virgen Macarena
  • Hospital Alvaro Cunqueiro

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Arm A: Placebo + Avastin + platinum-based chemotherapy

Arm B: Atezolizumab + Avastin+ platinum-based chemotherapy

Arm Description

The placebo arm: Placebo 1200 mg x 6 cycles q3wk or 800mg x 6 cycles q4wk during treatment with chemotherapy and Avastin, followed by placebo 1200mg q3wk until progression

The atezolizumab arm: Atezolizumab 1200 mg x 6 cycles q3wk or 800mg x 6 cycles q4wk during treatment with chemotherapy and Avastin, followed by atezolizumab 1200mg q3wk until progression .

Outcomes

Primary Outcome Measures

Efficacy: Progression free survival, where the date of progression is based on investigator assessment using the RECIST version 1.1

Secondary Outcome Measures

Efficacy: Overall survival (OS)
Efficacy: Time from date randomization to second subsequent therapy or date of death (TSST) whichever come first
patient reported outcome variables
questionnaire to be completed by patients and collected frequently during the study
Adverse events
frequency of adverse events according to MedRA terms

Full Information

First Posted
May 25, 2016
Last Updated
July 20, 2023
Sponsor
ARCAGY/ GINECO GROUP
Collaborators
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT02891824
Brief Title
ATALANTE: Atezolizumab vs Placebo Phase III Study in Late Relapse Ovarian Cancer Treated With Chemotherapy+Bevacizumab
Acronym
ATALANTE
Official Title
A Randomized, Double-blinded, Phase III Study of Atezolizumab Versus Placebo in Patients With Late Relapse of Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer Treated by Platinum-based Chemotherapy and Bevacizumab
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 22, 2016 (Actual)
Primary Completion Date
October 15, 2021 (Actual)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ARCAGY/ GINECO GROUP
Collaborators
Hoffmann-La Roche

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a phase III, randomized, double-blinded, comparative, multi-centre study to assess the efficacy of atezolizumab in combination with platinum-based chemotherapy plus bevacizumab administered concurrent to chemotherapy and in maintenance, in patients presenting epithelial ovarian cancer (including patients with primary peritoneal and / or fallopian tube adenocarcinoma) who have platinum-sensitive relapse (platinum-free interval > 6 months).
Detailed Description
Approximately 600 patients will be randomized using an Interactive Voice Response System /Interactive web system (IVR/IWR system) in a 1:2 ratio to the treatments as specified below: A. Arm A: Placebo + bevacizumab & platinum-based chemotherapy. The placebo arm will include one of 3 following regimens up to investigator choice (chosen prior to randomization) Carboplatin (day1)combined with gemcitabine (day1 & day8) and bevacizumab (day1) + placebo ( day1) x 6 cycles q3weeks followed by maintenance with bevacizumab ( day1) + placebo (day1) q3weeks until disease progression or Carboplatin (d1) combined with paclitaxel (day1) and bevacizumab (day1) + placebo (d1) x 6 cycles every 3weeks followed by maintenance with bevacizumab (day1) + placebo (day1) q3weeks until disease progression or Carboplatin (day1) combined with pegylated liposomal doxorubicin (PLD) (day1) and bevacizumab (day1 & 15) + placebo ( day1& 15) x 6 cycles every 4weeks followed by maintenance with bevacizumab (day1) + placebo (day1) q3weeks until disease progression. B. Arm B: Atezolizumab + bevacizumab & platinum-based chemotherapy The atezolizumab arm will include one of 3 following regimens up to investigator choice (chosen prior to randomization) Carboplatin (day1) combined with gemcitabine (day1 & d8) and bevacizumab (day1) + atezolizumab ( day1) x 6 cycles q3weeks followed by maintenance with bevacizumab (day1) + atezolizumab (day1) q3w until disease progression or Carboplatin (day1) combined with paclitaxel (day1) and bevacizumab ( day1) + atezolizumab (1200mg, d1) x 6 cycles every 3wk (day1) q3weeks until disease progression or Carboplatin (day1) combined with pegylated liposomal doxorubicin (PLD) (day1) and bevacizumab (day1 & 15) + atezolizumab (day1& 15) x 6 cycles every 4weeks followed by maintenance with bevacizumab (day1) + atezolizumab ( day1) q3weeks until disease progression. Before randomization to the study: A tumor biopsy should have been obtained and sent to the central laboratory PD-L1 status should be determined

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
PD-L1, Atezolizumab, Randomized, double blinded, first or second late relapse, progressive non-mucinous epithelial ovarian cancer, primary peritoneal adenocarcinoma and / or fallopian-tube adenocarcinoma, progression-free survival

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
614 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A: Placebo + Avastin + platinum-based chemotherapy
Arm Type
Placebo Comparator
Arm Description
The placebo arm: Placebo 1200 mg x 6 cycles q3wk or 800mg x 6 cycles q4wk during treatment with chemotherapy and Avastin, followed by placebo 1200mg q3wk until progression
Arm Title
Arm B: Atezolizumab + Avastin+ platinum-based chemotherapy
Arm Type
Experimental
Arm Description
The atezolizumab arm: Atezolizumab 1200 mg x 6 cycles q3wk or 800mg x 6 cycles q4wk during treatment with chemotherapy and Avastin, followed by atezolizumab 1200mg q3wk until progression .
Intervention Type
Drug
Intervention Name(s)
atezolizumab + avastin + platinum-based chemotherapy
Other Intervention Name(s)
Tecentriq
Intervention Description
atezolizumab will be administrated by intraveinous route at dose of 1200 mg or 800 mg during the induction period and will be continued in maintenance period at a dose of 1200mg until progression avastin will be administrated by intraveinous route at dose of 15mg/kg or 10 mg/kg during the induction period and will be continued in maintenance period of at a dose of 15mg/kg until progression platinum-based chemotherapy (Carboplatin combined with gemcitabine or paclitaxel or pegylated liposomal doxorubicin) will be administrated by intraveinous route at different doses during the induction period x 6 cycles
Intervention Type
Drug
Intervention Name(s)
placebo + avastin + platinum-based chemotherapy
Intervention Description
placebo will be administrated by intraveinous route at dose of 1200 mg or 800 mg during the induction period and will be continued in maintenance period at a dose of 1200mg until progression avastin will be administrated by intraveinous route at dose of 15mg/kg or 10 mg/kg during the induction period and will be continued in maintenance period of at a dose of 15mg/kg until progression platinum-based chemotherapy (Carboplatin combined with gemcitabine or paclitaxel or pegylated liposomal doxorubicin) will be administrated by intraveinous route at different doses during the induction period x 6 cycles
Primary Outcome Measure Information:
Title
Efficacy: Progression free survival, where the date of progression is based on investigator assessment using the RECIST version 1.1
Time Frame
An average of 19 months
Secondary Outcome Measure Information:
Title
Efficacy: Overall survival (OS)
Time Frame
To be assessed around 73 months
Title
Efficacy: Time from date randomization to second subsequent therapy or date of death (TSST) whichever come first
Time Frame
To be assessed around 73 months
Title
patient reported outcome variables
Description
questionnaire to be completed by patients and collected frequently during the study
Time Frame
to be assessed 19 months
Title
Adverse events
Description
frequency of adverse events according to MedRA terms
Time Frame
to be assessed 19 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
95 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female Patients must be ≥18 years of age. Signed informed consent and ability to comply with treatment and follow-up. Patients with histologically confirmed progressive non-mucinous epithelial ovarian cancer, primary peritoneal adenocarcinoma and / or fallopian-tube adenocarcinoma 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. If the location of the tumor renders tumor biopsy medically unsafe or not feasible, patient eligibility should be discussed with the sponsor. Patients whose disease has relapsed more than 6 months from the last dose of platinum before randomization: criterion for relapse can be according to RECIST v1.1, CA-125 (GCIG) or clinical symptoms 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. Patients with one or 2 prior lines of chemotherapy. The last line of chemotherapy should have included platinum. Availability at the study site of representative FFPE tumor sample from surgery during front line therapy, at best before chemotherapy Patients must have normal organ and bone marrow function : Haemoglobin ≥ 10.0 g/dL. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. Platelet count ≥ 100 x 109/L. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). 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. Serum creatinine ≤ 1.5 x institutional ULN, 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. Urine dipstick for proteinuria < 2+. If urine dipstick is ≥2+, 24-hours urine must demonstrate ≤1 g of protein in 24 hours. Normal blood pressure or adequately treated and controlled hypertension (systolic BP ≤ 140 mmHg and/or diastolic BP ≤ 90 mmHg). Eastern Cooperative Oncology Group (ECOG) performance status 0-1 For France only: In France, a subject will be eligible for randomization in this study only if either affiliated to, or a beneficiary of, a social security category Exclusion Criteria: Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors). Ovarian tumors of low malignant potential (e.g. borderline tumors) Patients with synchronous primary endometrial cancer unless both of the following criteria are met: stage < II, Less than 60 years old at the time of diagnosis of endometrial cancer with stage IA or IB grade 1 or 2, or stage IA grade 3 endometrioid adenocarcinoma OR ≥ 60 years old at the time of diagnosis of endometrial cancer with stage IA grade 1or 2 endometrioid adenocarcinoma. Patients with serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium are not eligible. Other malignancy within the last 5 years except cervix or breast in situ carcinoma, breast cancer ≥ 3 years free of disease and treatment, type I stage I endometrial cancer). Patients receiving radiotherapy within 6 weeks prior to study treatment. Major surgery within 4 weeks of starting study treatment or patients who have not completely recovered from the effects of any major surgery. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1, Cycle 1 Previous allogeneic bone marrow transplant or previous solid organ transplantation. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy is permitted). Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD1, or anti-PDL1 therapeutic antibodies or anti-CTLA 4. Treatment with systemic immunostimulatory agents (including but not limited to interferon-alpha (IFN-α) and interleukin-2 (IL-2) within 4 weeks or five half-lives of the drug (whichever is shorter) prior to Cycle 1, Day 1 Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed. Prophylactic anti-emetic corticosteroids will be avoided if possible in patients treated with pegylated liposomal doxorubicin-carboplatin or gemcitabine-carboplatin regimen. The use of corticosteroids is allowed as premedication for paclitaxel-based regimen and/or premedication in case of carboplatin hypersensitivity. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Are eligible patients with: a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone controlled Type 1 diabetes mellitus on a stable insulin regimen History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis. Radiation pneumonitis in the radiation field (fibrosis) detected on screening chest CT scan is permitted Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV). Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1 Administration of a live, attenuated vaccine within 4 weeks prior to Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study. Influenza vaccination should be given during influenza season only (example approximately October to March in the Northern Hemisphere). Patients must not receive live, attenuated influenza Current or recent (within 10 days prior to randomization) chronic use of aspirin > 325 mg/day. Prior history of hypertensive crisis (CTC-AE grade 4) or hypertensive encephalopathy. Inadequately controlled HTN (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg on antihypertensive medications) Clinically significant (e.g. active) cardiovascular disease, including: Myocardial infarction or unstable angina within ≤ 6 months of randomization, New York Heart Association (NYHA) ≥ grade 2 congestive heart failure (CHF), Poorly controlled cardiac arrhythmia despite medication (patients with rate controlled atrial fibrillation are eligible), Peripheral vascular disease grade ≥ 3 (e.g. symptomatic and interfering with activities of daily living [ADL] requiring repair or revision) Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome. Left ventricular ejection fraction defined by MUGA/ECHO below the institutional lower limit of normal (only applicable for patients intended to be treated with pegylated liposomal doxorubicin). Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub-Arachnoids Hemorrhage (SAH) within 6 months prior to randomization. History or evidence of hemorrhagic disorders within 6 months prior to randomization. Evidence of bleeding diathesis or significant coagulopathy (in the absence of coagulation). History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of suspected spinal cord compression. History or evidence upon neurological examination of central nervous system (CNS) disease, unless adequately treated with standard medical therapy (e.g. uncontrolled seizures). Significant traumatic injury during 4 weeks prior to randomization. Non-healing wound, active ulcer or bone fracture. Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require 3 weekly wound examinations. History of VEGF therapy related abdominal fistula or gastrointestinal perforation. Current, clinically relevant bowel obstruction, including sub-occlusive disease, related to underlying disease. Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment related complications. Women of childbearing potential (<2 years after last menstruation and not surgically sterile) not willing to use highly-effective means of contraception (Appendix 1) during the study and for 6 months after the last dose of study medication Pregnant or lactating women. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation. Known hypersensitivity reaction or allergy to drugs chemically related to bevacizumab, carboplatin, gemcitabine, paclitaxel, pegylated liposomal doxorubicin, or their excipients that contraindicates the subject's participation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Emmanuel KURTZ
Organizational Affiliation
GINECO - Institut de cancérologie Strasbourg Europe
Official's Role
Principal Investigator
Facility Information:
Facility Name
Krankenhaus der Barmherzigen Brüder Graz
City
Graz
ZIP/Postal Code
8020
Country
Austria
Facility Name
Medical University of Graz
City
Graz
ZIP/Postal Code
8036
Country
Austria
Facility Name
Medical University of Innsbruck
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
Facility Name
Medical University of Vienna
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Uz Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
General University Hospital in Prague
City
Prague
ZIP/Postal Code
128 51
Country
Czechia
Facility Name
ICO Paul Papin
City
Angers
Country
France
Facility Name
Sainte-Catherine Institut du Cancer Avignon-Provence
City
Avignon
Country
France
Facility Name
CHRU Jean Minjoz
City
Besançon
Country
France
Facility Name
Clinique Tivoli
City
Bordeaux
Country
France
Facility Name
Institut Bergonié
City
Bordeaux
Country
France
Facility Name
Centre François Baclesse
City
Caen
Country
France
Facility Name
Centre Jean Perrin
City
Clermont-Ferrand
Country
France
Facility Name
Groupe Hospitalier Mutualiste de Grenoble
City
Grenoble
Country
France
Facility Name
Hôpital Michallon - Centre Hospitalier Universitaire de Grenoble
City
Grenoble
Country
France
Facility Name
Centre Hospitalier Départemental Les Oudairies
City
La Roche sur Yon
Country
France
Facility Name
Centre Oscar Lambret
City
Lille
Country
France
Facility Name
Centre Léon Bérard
City
Lyon
Country
France
Facility Name
Institut Paoli Calmettes
City
Marseille
Country
France
Facility Name
Hôpital de Mont-de-Marsan
City
Mont de Marsan
Country
France
Facility Name
ICM Val d'Aurelle
City
Montpellier
Country
France
Facility Name
Centre Azuréen de Cancérologie
City
Mougins
Country
France
Facility Name
ORACLE - Centre d'Oncologie de Gentilly
City
Nancy
Country
France
Facility Name
Hôpital Privé du Confluent, S.A.S.
City
Nantes
Country
France
Facility Name
Centre Antoine Lacassagne
City
Nice
Country
France
Facility Name
CHU Nîmes - Institut de Cancérologie du Gard
City
Nimes
Country
France
Facility Name
Centre Hospitalier Régional d'Orléans
City
Orléans
Country
France
Facility Name
Groupe Hospitalier Diaconesses-Croix Saint Simon
City
Paris
Country
France
Facility Name
Groupe Hospitalier Saint-Joseph
City
Paris
Country
France
Facility Name
Hôpital Cochin
City
Paris
Country
France
Facility Name
Hôpital Européen Georges Pompidou
City
Paris
Country
France
Facility Name
Hôpital Tenon
City
Paris
Country
France
Facility Name
Institut Curie - Hopital Claudius Régaud
City
Paris
Country
France
Facility Name
Centre Hospitalier Lyon Sud
City
Pierre Bénite
Country
France
Facility Name
Centre CARIO - HPCA
City
Plérin
Country
France
Facility Name
Hôpital de la Milétrie - Centre Hospitalier Universitaire de Poitiers - Pôle Régional de Cancérologie
City
Poitiers
Country
France
Facility Name
Centre Eugène Marquis
City
Rennes
Country
France
Facility Name
Hôpital René Huguenin, Institut Curie
City
Saint-Cloud
Country
France
Facility Name
ICO Centre René Gauducheau
City
Saint-Herblain
Country
France
Facility Name
Centre Paul Strauss
City
Strasbourg
Country
France
Facility Name
Institut de Cancérologie Strasbourg Europe (ICANS)
City
Strasbourg
Country
France
Facility Name
Clinique Pasteur
City
Toulouse
Country
France
Facility Name
Institut Claudius Regaud
City
Toulouse
Country
France
Facility Name
ICL Institut de Cancérologie de Lorraine
City
Vandoeuvre Les Nancy
Country
France
Facility Name
Gustave Roussy
City
Villejuif
Country
France
Facility Name
Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin
City
Berlin
Country
Germany
Facility Name
Universitätsklinikum Carl Gustav Carus
City
Dresden
Country
Germany
Facility Name
Universitatsklinikum Dusseldorf
City
Dusseldorf
Country
Germany
Facility Name
Kliniken Essen Mitte, Evang. Huyssens-Stiftung
City
Essen
ZIP/Postal Code
45136
Country
Germany
Facility Name
Universitätsklinikum Essen
City
Essen
Country
Germany
Facility Name
Universitätsklinikum Hamburg-Eppendorf
City
Hamburg
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
Country
Germany
Facility Name
Universitätsklinikum Jena
City
Jena
Country
Germany
Facility Name
Städtisches Klinikum Karlsruhe
City
Karlsruhe
Country
Germany
Facility Name
Klinikum der Universität München - LMU, Campus Großhadern
City
München
Country
Germany
Facility Name
Klinikum rechts der Isar, Technischen Universität München
City
München
Country
Germany
Facility Name
Sana Klinikum Offenbach
City
Offenbach
Country
Germany
Facility Name
Studienzentrum Onkologie Ravensburg
City
Ravensburg
Country
Germany
Facility Name
Universitatsklinikum Tübingen
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Universitätsklinikum Ulm
City
ULM
Country
Germany
Facility Name
Klinikum Worms
City
Worms
ZIP/Postal Code
67550
Country
Germany
Facility Name
Sharre Zedek Medical Centre
City
Jerusalem
Country
Israel
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clínic Barcelona
City
Barcelona
ZIP/Postal Code
8036
Country
Spain
Facility Name
Hospital San Pedro de Alcántara
City
Cáceres
ZIP/Postal Code
10003
Country
Spain
Facility Name
Hospital Universitari de Girona ICO Girona (Dr. Josep Trueta)
City
Girona
ZIP/Postal Code
17007
Country
Spain
Facility Name
Hospital Universitario Clínico San Carlos
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Universitario HM Sanchinarro
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Hospital Central Universitario Virgen de la Arrixaca
City
Murcia
ZIP/Postal Code
30120
Country
Spain
Facility Name
Hospital Universitario Son Espases
City
Palma De Mallorca
ZIP/Postal Code
7120
Country
Spain
Facility Name
Hospital Universitario Donostia
City
San Sebastián
ZIP/Postal Code
20014
Country
Spain
Facility Name
Hospital Universitario Virgen Macarena
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Facility Name
Hospital Alvaro Cunqueiro
City
Vigo
ZIP/Postal Code
36312
Country
Spain

12. IPD Sharing Statement

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ATALANTE: Atezolizumab vs Placebo Phase III Study in Late Relapse Ovarian Cancer Treated With Chemotherapy+Bevacizumab

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