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

NCT02891824 | Completed Phase 3 DMC

• 1 other identifier: GINECO-OV236b
• Study Type: interventional
• Target: 614
• Locations: 7 countries
• Sites: 75

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• 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

• patient reported outcome variables

  to be assessed 19 months

• Adverse events

  to be assessed 19 months

Study Arms (2)

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

Drug: placebo + avastin + platinum-based chemotherapy

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 .

Drug: atezolizumab + avastin + platinum-based chemotherapy

Interventions

atezolizumab + avastin + platinum-based chemotherapy DRUG

* 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

Also known as: Tecentriq

Arm B: Atezolizumab + Avastin+ platinum-based chemotherapy

placebo + avastin + platinum-based chemotherapy DRUG

* 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

Arm A: Placebo + Avastin + platinum-based chemotherapy

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ARCAGY/ GINECO GROUP: lead
• Hoffmann-La Roche: collaborator

Study Sites (75)

Krankenhaus der Barmherzigen Brüder Graz

Graz, 8020, Austria

Location

Medical University of Graz

Graz, 8036, Austria

Location

Medical University of Innsbruck

Innsbruck, 6020, Austria

Location

Medical University of Vienna

Vienna, 1090, Austria

Location

UZ Gent

Ghent, 9000, Belgium

Location

Uz Leuven

Leuven, 3000, Belgium

Location

General University Hospital in Prague

Prague, 128 51, Czechia

Location

ICO Paul Papin

Angers, France

Location

Sainte-Catherine Institut du Cancer Avignon-Provence

Avignon, France

Location

CHRU Jean Minjoz

Besançon, France

Location

Clinique Tivoli

Bordeaux, France

Location

Institut Bergonié

Bordeaux, France

Location

Centre François Baclesse

Caen, France

Location

Centre Jean Perrin

Clermont-Ferrand, France

Location

Groupe Hospitalier Mutualiste de Grenoble

Grenoble, France

Location

Hôpital Michallon - Centre Hospitalier Universitaire de Grenoble

Grenoble, France

Location

Centre Hospitalier Départemental Les Oudairies

La Roche-sur-Yon, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

Institut Paoli Calmettes

Marseille, France

Location

Hôpital de Mont-de-Marsan

Mont-de-Marsan, France

Location

ICM Val d'Aurelle

Montpellier, France

Location

Centre Azuréen de Cancérologie

Mougins, France

Location

ORACLE - Centre d'Oncologie de Gentilly

Nancy, France

Location

Hôpital Privé du Confluent, S.A.S.

Nantes, France

Location

Centre Antoine Lacassagne

Nice, France

Location

CHU Nîmes - Institut de Cancérologie du Gard

Nîmes, France

Location

Centre Hospitalier Régional d'Orléans

Orléans, France

Location

Groupe Hospitalier Diaconesses-Croix Saint Simon

Paris, France

Location

Groupe Hospitalier Saint-Joseph

Paris, France

Location

Hôpital Cochin

Paris, France

Location

Hôpital Européen Georges Pompidou

Paris, France

Location

Hôpital Tenon

Paris, France

Location

Institut Curie - Hopital Claudius Régaud

Paris, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Location

Centre CARIO - HPCA

Plérin, France

Location

Hôpital de la Milétrie - Centre Hospitalier Universitaire de Poitiers - Pôle Régional de Cancérologie

Poitiers, France

Location

Centre Eugène Marquis

Rennes, France

Location

Hôpital René Huguenin, Institut Curie

Saint-Cloud, France

Location

ICO Centre René Gauducheau

Saint-Herblain, France

Location

Centre Paul Strauss

Strasbourg, France

Location

Institut de Cancérologie Strasbourg Europe (ICANS)

Strasbourg, France

Location

Clinique Pasteur

Toulouse, France

Location

Institut Claudius Regaud

Toulouse, France

Location

ICL Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, France

Location

Gustave Roussy

Villejuif, France

Location

Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin

Berlin, Germany

Location

Universitätsklinikum Carl Gustav Carus

Dresden, Germany

Location

Universitatsklinikum Dusseldorf

Düsseldorf, Germany

Location

Kliniken Essen Mitte, Evang. Huyssens-Stiftung

Essen, 45136, Germany

Location

Universitätsklinikum Essen

Essen, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Germany

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

Universitätsklinikum Jena

Jena, Germany

Location

Städtisches Klinikum Karlsruhe

Karlsruhe, Germany

Location

Klinikum der Universität München - LMU, Campus Großhadern

München, Germany

Location

Klinikum rechts der Isar, Technischen Universität München

München, Germany

Location

Sana Klinikum Offenbach

Offenbach, Germany

Location

Studienzentrum Onkologie Ravensburg

Ravensburg, Germany

Location

Universitatsklinikum Tübingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, Germany

Location

Klinikum Worms

Worms, 67550, Germany

Location

Sharre Zedek Medical Centre

Jerusalem, Israel

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic Barcelona

Barcelona, 8036, Spain

Location

Hospital San Pedro de Alcántara

Cáceres, 10003, Spain

Location

Hospital Universitari de Girona ICO Girona (Dr. Josep Trueta)

Girona, 17007, Spain

Location

Hospital Universitario Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

Hospital Central Universitario Virgen de la Arrixaca

Murcia, 30120, Spain

Location

Hospital Universitario Son Espases

Palma de Mallorca, 7120, Spain

Location

Hospital Universitario Donostia

San Sebastián, 20014, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital Alvaro Cunqueiro

Vigo, 36312, Spain

Location

Related Publications (1)

• 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.

  PMID: 37643382 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

atezolizumab; Bevacizumab; Platinum Compounds

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Inorganic Chemicals

Study Officials

• Jean-Emmanuel KURTZ

  GINECO - Institut de cancérologie Strasbourg Europe

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2016
• First Posted: September 8, 2016
• Study Start: September 22, 2016
• Primary Completion: October 15, 2021
• Study Completion: February 22, 2024
• Last Updated: February 11, 2025

Record last verified: 2025-02

Locations

ES (12); AU (4); CZ (1); DE (16); BE (2); FR (39); IL (1)