Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Hoffmann-La Roche | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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).
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)
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)
Before randomization to the study:
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: Placebo + Avastin + platinum-based chemotherapy | Placebo Comparator | 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 B: Atezolizumab + Avastin+ platinum-based chemotherapy | Experimental | 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 . |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| atezolizumab + avastin + platinum-based chemotherapy | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy: Progression free survival, where the date of progression is based on investigator assessment using the RECIST version 1.1 | An average of 19 months |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy: Overall survival (OS) | To be assessed around 73 months | |
| Efficacy: Time from date randomization to second subsequent therapy or date of death (TSST) whichever come first | To be assessed around 73 months |
Not provided
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.
Patients whose disease has relapsed more than 6 months from the last dose of platinum before randomization:
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 :
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:
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
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:
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:
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
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Jean-Emmanuel KURTZ | GINECO - Institut de cancérologie Strasbourg Europe | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Krankenhaus der Barmherzigen Brüder Graz | Graz | 8020 | Austria | |||
| Medical University of Graz |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37643382 | Derived | Kurtz JE, Pujade-Lauraine E, Oaknin A, Belin L, Leitner K, Cibula D, Denys H, Rosengarten O, Rodrigues M, de Gregorio N, Martinez Garcia J, Petru E, Kocian R, Vergote I, Pautier P, Schmalfeldt B, Gaba L, Polterauer S, Mouret Reynier MA, Sehouli J, Churruca C, Selle F, Joly F, D'Hondt V, Bultot-Boissier E, Lebreton C, Lotz JP, Largillier R, Heudel PE, Heitz F; ATALANTE/ENGOT-ov29 Investigators. Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial. J Clin Oncol. 2023 Oct 20;41(30):4768-4778. doi: 10.1200/JCO.23.00529. Epub 2023 Aug 29. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| placebo + avastin + platinum-based chemotherapy | Drug |
|
|
| patient reported outcome variables | questionnaire to be completed by patients and collected frequently during the study | to be assessed 19 months |
| Adverse events | frequency of adverse events according to MedRA terms | to be assessed 19 months |
| Graz |
| 8036 |
| Austria |
| Medical University of Innsbruck | Innsbruck | 6020 | Austria |
| Medical University of Vienna | Vienna | 1090 | Austria |
| UZ Gent | Ghent | 9000 | Belgium |
| Uz Leuven | Leuven | 3000 | Belgium |
| General University Hospital in Prague | Prague | 128 51 | Czechia |
| ICO Paul Papin | Angers | France |
| Sainte-Catherine Institut du Cancer Avignon-Provence | Avignon | France |
| CHRU Jean Minjoz | Besançon | France |
| Clinique Tivoli | Bordeaux | France |
| Institut Bergonié | Bordeaux | France |
| Centre François Baclesse | Caen | France |
| Centre Jean Perrin | Clermont-Ferrand | France |
| Groupe Hospitalier Mutualiste de Grenoble | Grenoble | France |
| Hôpital Michallon - Centre Hospitalier Universitaire de Grenoble | Grenoble | France |
| Centre Hospitalier Départemental Les Oudairies | La Roche-sur-Yon | France |
| Centre Oscar Lambret | Lille | France |
| Centre Léon Bérard | Lyon | France |
| Institut Paoli Calmettes | Marseille | France |
| Hôpital de Mont-de-Marsan | Mont-de-Marsan | France |
| ICM Val d'Aurelle | Montpellier | France |
| Centre Azuréen de Cancérologie | Mougins | France |
| ORACLE - Centre d'Oncologie de Gentilly | Nancy | France |
| Hôpital Privé du Confluent, S.A.S. | Nantes | France |
| Centre Antoine Lacassagne | Nice | France |
| CHU Nîmes - Institut de Cancérologie du Gard | Nîmes | France |
| Centre Hospitalier Régional d'Orléans | Orléans | France |
| Groupe Hospitalier Diaconesses-Croix Saint Simon | Paris | France |
| Groupe Hospitalier Saint-Joseph | Paris | France |
| Hôpital Cochin | Paris | France |
| Hôpital Européen Georges Pompidou | Paris | France |
| Hôpital Tenon | Paris | France |
| Institut Curie - Hopital Claudius Régaud | Paris | France |
| Centre Hospitalier Lyon Sud | Pierre-Bénite | France |
| Centre CARIO - HPCA | Plérin | France |
| Hôpital de la Milétrie - Centre Hospitalier Universitaire de Poitiers - Pôle Régional de Cancérologie | Poitiers | France |
| Centre Eugène Marquis | Rennes | France |
| Hôpital René Huguenin, Institut Curie | Saint-Cloud | France |
| ICO Centre René Gauducheau | Saint-Herblain | France |
| Centre Paul Strauss | Strasbourg | France |
| Institut de Cancérologie Strasbourg Europe (ICANS) | Strasbourg | France |
| Clinique Pasteur | Toulouse | France |
| Institut Claudius Regaud | Toulouse | France |
| ICL Institut de Cancérologie de Lorraine | Vandœuvre-lès-Nancy | France |
| Gustave Roussy | Villejuif | France |
| Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin | Berlin | Germany |
| Universitätsklinikum Carl Gustav Carus | Dresden | Germany |
| Universitatsklinikum Dusseldorf | Düsseldorf | Germany |
| Kliniken Essen Mitte, Evang. Huyssens-Stiftung | Essen | 45136 | Germany |
| Universitätsklinikum Essen | Essen | Germany |
| Universitätsklinikum Hamburg-Eppendorf | Hamburg | Germany |
| Medizinische Hochschule Hannover | Hanover | Germany |
| Universitätsklinikum Jena | Jena | Germany |
| Städtisches Klinikum Karlsruhe | Karlsruhe | Germany |
| Klinikum der Universität München - LMU, Campus Großhadern | München | Germany |
| Klinikum rechts der Isar, Technischen Universität München | München | Germany |
| Sana Klinikum Offenbach | Offenbach | Germany |
| Studienzentrum Onkologie Ravensburg | Ravensburg | Germany |
| Universitatsklinikum Tübingen | Tübingen | 72076 | Germany |
| Universitätsklinikum Ulm | Ulm | Germany |
| Klinikum Worms | Worms | 67550 | Germany |
| Sharre Zedek Medical Centre | Jerusalem | Israel |
| Hospital Universitari Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital Clínic Barcelona | Barcelona | 8036 | Spain |
| Hospital San Pedro de Alcántara | Cáceres | 10003 | Spain |
| Hospital Universitari de Girona ICO Girona (Dr. Josep Trueta) | Girona | 17007 | Spain |
| Hospital Universitario Clínico San Carlos | Madrid | 28040 | Spain |
| Hospital Universitario La Paz | Madrid | 28046 | Spain |
| Hospital Universitario HM Sanchinarro | Madrid | 28050 | Spain |
| Hospital Central Universitario Virgen de la Arrixaca | Murcia | 30120 | Spain |
| Hospital Universitario Son Espases | Palma de Mallorca | 7120 | Spain |
| Hospital Universitario Donostia | San Sebastián | 20014 | Spain |
| Hospital Universitario Virgen Macarena | Seville | 41009 | Spain |
| Hospital Alvaro Cunqueiro | Vigo | 36312 | Spain |
| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C000594389 | atezolizumab |
| D000068258 | Bevacizumab |
| D017671 | Platinum Compounds |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D007287 | Inorganic Chemicals |
Not provided
Not provided