Platinum Chemotherapy Plus Paclitaxel With Bevacizumab and Atezolizumab in Metastatic Carcinoma of the Cervix

NCT03556839 | Completed Phase 3 DMC FDA Drug

• 7 other identifiers: ENGOT-Cx10 / BEATcc2018-000367-83ENGOT-Cx10GEICO 68-CJGOG1084GOG-30302024-514179-17-00
• Study Type: interventional
• Target: 410
• Locations: 8 countries
• Sites: 72

Brief Summary

The study will integrate the efficacy of combining the anti programmed death-ligand 1 (anti-PD-L1) agent atezolizumab with the current standard of care in Stage IVB , persistent or recurrent carcinoma of the cervix, namely cisplatin or carboplatin/paclitaxel/bevacizumab. It will be explored the combination of bevacizumab plus atezolizumab, with no patient selection based on PD-L1 expression, allowing an all-comer assessment of atezolizumab activity. The study is a randomized open label phase III trial to investigate the impact of atezolizumab in combination with bevacizumab and cisplatin or carboplatin /paclitaxel chemotherapy on overall survival and will employ the intent to treat principle, and random assignment to one of the 2 arms will be balanced according to disease histology (squamous cell carcinoma vs adenocarcinoma), prior platinum therapy as a radiation sensitizer (no prior cis-Radiotherapy (RT) versus prior cis-RT) and chemotherapy backbone (cisplatin vs carboplatin). This trial will be run in an open label design due to the following considerations: the control arm is the standard of care for women diagnosed with metastatic, persistant or recurrent cervical cancer because of its impact on overall survival and the primary endpoint of the study is overall survival (OS), so blinding is not needed to ensure a robust assessment.

Conditions

Carcinoma of the Cervix, Stage IVB

Keywords

Cervix; Carcinoma; Atezolizumab

Outcome Measures

Primary Outcomes (2)

• Progression-free survival

  Time from the date of randomization to the date of first documentation of disease progression or death due to any cause, whichever occurs first based on investigator assessment using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)

  48 months

• Overall survival

  Time from the date of randomization to the date of death due to any cause

  48 months

Secondary Outcomes (6)

• Objective Response Rate

  48 months

• Duration of response

  48 months

• Incidence of Treatment-Emergent Adverse Events of combining atezolizumab to chemotherapy plus bevacizumab compared to cisplatin or carboplatin/paclitaxel (CP) plus bevacizumab.

  48 months

• First subsequent therapy

  48 months

• Progression-free survival 2

  48 months

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Cisplatin 50mg/m2 or carboplatin AUC 5 + paclitaxel 175mg/m2+ bevacizumab 15mg/kg i.v D1 Q3W. Patients who achieve a complete response after ≥6 treatment cycles may be allowed to continue only on biologic therapy, namely bevacizumab, upon investigator discussion.

Drug: Bevacizumab; Drug: Cisplatin/Carboplatin; Drug: Paclitaxel

Arm B

EXPERIMENTAL

cisplatin 50mg/m2 or carboplatin AUC 5 + paclitaxel 175mg/m2 + bevacizumab 15mg/kg + atezolizumab 1200mg i.v, D1 Q3W.Patients who achieve a complete response after ≥6 treatment cycles may be allowed to continue only on biologics therapy, namely bevacizumab plus atezolizumab, upon investigator discussion.

Drug: Atezolizumab; Drug: Bevacizumab; Drug: Cisplatin/Carboplatin; Drug: Paclitaxel

Interventions

Atezolizumab DRUG

Intravenous Infusion

Also known as: Tecentriq

Arm B

Bevacizumab DRUG

Intravenous Infusion

Also known as: Avastin

Arm A; Arm B

Cisplatin/Carboplatin DRUG

Intravenous Infusion

Arm A; Arm B

Paclitaxel DRUG

Intravenous Infusion

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female patients
• 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 before any study-specific procedure
• Able (in the investigator´s judgment) to comply with the study protocol
• GOG/Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Life expectancy ≥3 months
• No prior systemic anti-cancer therapy for metastatic or recurrent disease.
• Measureable disease by RECIST v1.1 criteria.
• A tumor specimen is mandatory at study entry.
• Adequate organ function:
• Hemoglobin ≥9 g/dL ANC ≥1.5 × 109/L Lymphocyte count ≥0.5 × 109/L Platelet count ≥100 x 109/L
• Adequate liver function:
• Serum albumin ≥2.5 g/dL Total serum bilirubin ≤1.5 ×ULN AST and ALT ≤2.5 × upper limit normal (ULN) or ≤5 × ULN if tumor involvement (liver) is present
• Adequate renal function:
• Patients with serum creatinine \<1.5 × ULN Urine dipstick for proteinuria \<2+.
• Adequate coagulation:

You may not qualify if:

• Disease that is suitable for local therapy administered with curative intent
• Prior radiotherapy delivered using cobalt (rather than a linear accelerator)
• Patients with Stage IVA not amendable to concurrent chemo-radiation as primary treatment will not be eligible.
• Ongoing disease involving the bladder or rectum at screening/baseline
• Evidence of abdominal free air
• Bilateral hydronephrosis, unless it can be alleviated by ureteral stent(s) or percutaneous drainage
• Patients previously treated with chemotherapy except when used concurrently with radiation therapy. Patients who have received either concurrent paclitaxel with radiation therapy or carboplatin/paclitaxel as adjuvant therapy are ineligible for the study.
• Prior treatment with any anti-VEGF drug, including bevacizumab, CD137 agonists or immune checkpoint blockade therapies, anti-PD1, or anti-PDL1 therapeutic antibodies or anti-CTLA 4.
• Patients with a concomitant malignancy other than non-melanoma skin cancer. Patients with a prior invasive malignancy (except non-melanoma skin cancer ) who have had any evidence of disease within the last 5 years or whose prior malignancy treatment contraindicates the current protocol therapy.
• Known brain metastases or spinal cord compression. It is mandatory to perform a scan of the brain in cases of suspected brain metastases (CT or MRI) or spinal cord compression (MRI).
• History or evidence, following a neurological examination, of central nervous system (CNS) disorders, unless properly treated with standard medical treatment,(e.g. uncontrolled epileptic seizures). History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study.
• Patients with serious non-healing wound, ulcer, or bone fracture.
• Acute intestinal obstruction or sub-occlusion episode in the last 6 months.
• Active GI bleeding or GI ulcer
• History of Crohn's disease or inflammatory bowel disease

Sponsors & Collaborators

• Grupo Español de Investigación en Cáncer de Ovario: lead
• ARCAGY/ GINECO GROUP: collaborator
• MaNGO: collaborator
• NSGO: collaborator
• Japanese Gynecologic Oncology Group: collaborator
• Gynecologic Oncology Group Foundation: collaborator
• AGO Study Group: collaborator
• Apices Soluciones S.L.: collaborator
• Hoffmann-La Roche: collaborator
• Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies: collaborator

Study Sites (72)

Willis Knighton Cancer Center

Shreveport, Louisiana, 71103, United States

Location

Massey Cancer Center

Richmond, Virginia, 980037, United States

Location

ICO Paul Papin

Angers, 49055, France

Location

CHU Jean Minjoz

Besançon, France

Location

Institut Bergonié

Bordeaux, France

Location

Centre François Baclesse

Caen, France

Location

Centre Oscar Lambret

Lille, 59000, France

Location

Centre Léon Bérard

Lyon, France

Location

ICM Val d'Aurelle

Montpellier, France

Location

Hôpital Privé du Confluent S.A.S.

Nantes, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Groupe Hospitalier Diaconesses-Croix Saint-Simon

Paris, France

Location

HEGP

Paris, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Location

Centre CARIO-HPCA

Plérin, France

Location

ICO Centre René Gauducheau

Saint-Herblain, France

Location

Hôpitaux Universitaires

Strasbourg, France

Location

Institut Claudius Régaud

Toulouse, France

Location

Gustave Roussy

Villejuif, France

Location

Universitätsmedizin Mainz

Mainz, 55131, Germany

Location

Helios-Klinikum Wuppertal

Wuppertal, 42283, Germany

Location

Fondazione Del Piemonte Per L'Oncologia

Candiolo, Italy

Location

Azienda Ospedaliero-Universitaria Di Ferrara

Ferrara, Italy

Location

Ospedale Lecce 'Vito Fazzi'

Lecce, Italy

Location

ASST Lecco

Lecco, Italy

Location

Irst Irccs

Meldola FC, Italy

Location

Irccs S. Raffaele - Milano

Milan, Italy

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

Ospedale San Gerardo

Monza, Italy

Location

Istituto Nazionale Tumori Di Napoli Irccs Pascale

Naples, Italy

Location

Istituto Oncologico Veneto (IOV) IRCCS

Padova, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, Italy

Location

AUSL Romagna - P.O. di Ravenna, Lugo, Faenza, Rimini e Cattolica

Ravenna, Italy

Location

Azienda Usl - Irccs Di Reggio Emilia

Reggio Emilia, Italy

Location

Policlinico Universitario A. Gemelli

Roma, Italy

Location

AOU Città della Salute e della Scienza di Torino, Presidio Sant'Anna

Torino, Italy

Location

Ospedale Ordine Mauriziano

Torino, Italy

Location

Azienda Sanitaria Universitaria Integrata Di Udine

Udine, Italy

Location

Kurume University Hospital

Fukuoka, Japan

Location

Saitama medical university international medical center

Hidaka, Japan

Location

Hokkaido Cancer Center

Hokkaido, Japan

Location

Hyogo Cancer Center

Hyōgo, Japan

Location

Cancer Institute Hospital

Kōtoku, Japan

Location

Niigata University Medical & Dental Hospital

Niigata, Japan

Location

Shizuoka Cancer Center

Shizuoka, Japan

Location

Keio University Hospital

Tokyo, Japan

Location

Haukeland University Hospital

Bergen, Norway

Location

Oslo University Hospital

Oslo, Norway

Location

University Hospital of North Norway

Tromsø, Norway

Location

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Hospital de la Vall d'Hebron

Barcelona, Barcelona, 08035, Spain

Location

H. Clínic Barcelona

Barcelona, Barcelona, 08036, Spain

Location

Intitut Català d' Oncolgia L' Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Parc Taulí

Sabadell, Barcelona, 08208, Spain

Location

Hospital Reina Sofía Cordoba

Córdoba, Cordoba, 14004, Spain

Location

Hospital Universitario Donostia- Donostia Unibertsitate Ospitalea

Donostia / San Sebastian, Gipuzkoa, 20014, Spain

Location

ICO Girona

Girona, Girona, 17007, Spain

Location

Hospital Ramon y Cajal

Madrid, Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

Location

Hospital Clinico Universitario Virgen Arrixaca

Murcia, Murcia, 30120, Spain

Location

Complejo Hospitalario Regional de Málaga

Málaga, Málaga, 29010, Spain

Location

Hosptial Clinico Universitario de Santiago de Compostela

Santiago de Compostela, Santiago de Compostela, 15706, Spain

Location

Instituto Valenciano de Oncología

Valencia, Valencia, 46009, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Valencia, 46010, Spain

Location

Hospital Miguel Servet

Zaragoza, Zaragoza, 50009, Spain

Location

Hospital Virgen de la Salud

Toledo, 45004, Spain

Location

Hospital Quirón de Valencia

Valencia, 46010, Spain

Location

Lindköping University Hospital

Linköping, Sweden

Location

Skane University Hospital

Lund, Sweden

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Uppsala University Hospital

Uppsala, Sweden

Location

Related Publications (3)

• Takekuma M, Nishio S, Yamaguchi S, Yunokawa M, Nishio H, Nishino K, Kurosaki A, Minobe S, Villacampa G, Oaknin A, Okamoto A. Atezolizumab, bevacizumab, and platinum chemotherapy in cervical cancer: results of Japanese population from BEATcc. J Gynecol Oncol. 2025 Nov;36(6):e116. doi: 10.3802/jgo.2025.36.e116. Epub 2025 May 19.

  PMID: 40968753 DERIVED

• Oaknin A, Gladieff L, Martinez-Garcia J, Villacampa G, Takekuma M, De Giorgi U, Lindemann K, Woelber L, Colombo N, Duska L, Leary A, Godoy-Ortiz A, Nishio S, Angelergues A, Rubio MJ, Farinas-Madrid L, Yamaguchi S, Lorusso D, Ray-Coquard I, Manso L, Joly F, Alarcon J, Follana P, Romero I, Lebreton C, Perez-Fidalgo JA, Yunokawa M, Dahlstrand H, D'Hondt V, Randall LM; ENGOT-Cx10-GEICO 68-C-JGOG1084-GOG-3030 Investigators. Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet. 2024 Jan 6;403(10421):31-43. doi: 10.1016/S0140-6736(23)02405-4. Epub 2023 Dec 1.

  PMID: 38048793 DERIVED

• Grau JF, Farinas-Madrid L, Oaknin A. A randomized phase III trial of platinum chemotherapy plus paclitaxel with bevacizumab and atezolizumab versus platinum chemotherapy plus paclitaxel and bevacizumab in metastatic (stage IVB), persistent, or recurrent carcinoma of the cervix: the BEATcc study (ENGOT-Cx10/GEICO 68-C/JGOG1084/GOG-3030). Int J Gynecol Cancer. 2020 Jan;30(1):139-143. doi: 10.1136/ijgc-2019-000880. Epub 2019 Oct 23.

  PMID: 31645423 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Carcinoma

Interventions

atezolizumab; Bevacizumab; Cisplatin; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Ana Oaknin, MD PhD

  Vall d´Hebron University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2018
• First Posted: June 14, 2018
• Study Start: September 25, 2018
• Primary Completion: August 31, 2025
• Study Completion: August 31, 2025
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (19); SE (4); JP (8); DE (2); NO (3); US (2); IT (17); FR (17)