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

Completed · Phase 3

Conditions studied: Carcinoma of the Cervix, Stage IVB

In brief

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.

Key facts

Study ID

NCT03556839

Run by

Grupo Español de Investigación en Cáncer de Ovario

People needed

410

Starts

2018-09-25

Expected to finish

2025-08-31

Last updated by the study team

2026-04-21

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

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
• Histologically- or cytologically-confirmed diagnosis of metastatic (stage IVB), persistent, or recurrent cervical cancer (histologies other than squamous cell, adenocarcinoma, or adenosquamous will be excluded) not amenable for curative treatment with surgery and/or radiation therapy. The inclusion of patients with adenocarcinoma histology will be capped to 20% of the whole study population.
• 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:
• Blood coagulation parameters (PTT, PT/INR): PT such that international normalized ratio (INR) is ≤ 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thromboembolus) and a PTT <1.5 × ULN.
• Negative Test Results for Hepatitis:
• Negative hepatitis B surface antigen (HBsAg) test at screening Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening.The HBV DNA test will be performed only for patients who have a positive total HBcAb test.
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening.The HCV RNA test will be performed only for patients who have a positive HCV antibody test.
• Toxicities related to previous treatments must be recovered to < grade 2 (with the exception of alopecia).
• Female participants must be postmenopausal (≥ 12 months of non-therapy-induced amenorrhoea) or surgically sterile (absence of ovaries and/or uterus, or who received therapeutic radiation to the pelvis) or otherwise have a negative serum pregnancy test within 7 days of the first study treatment and agree to abstain from heterosexual intercourse or use single or combined contraceptive methods that result in a failure rate of <1% per year during the whole treatment period of the study and for at least 5 months (if the last study dose contained atezolizumab) or 6 months (if the last study dose contained bevacizumab) after the last dose of study treatment.
• Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal or postovulation methods) and withdrawal are not acceptable methods of contraception

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
• Prior bowel resection ≤6 weeks preceding first study dose
• History of diverticulitis requiring medical intervention
• NCI CTCAE (version 5.0) grade ≥2 enteritis
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1, Cycle 1.
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1, Cycle 1.
• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels.
• Current or recent (within 10 days before the first dose of study drug) chronic daily treatment with aspirin (>325 mg/day), clopidogrel (>75 mg/day), or current or recent (within 10 days before first dose of bevacizumab) use of therapeutic oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes.
• Patients with pre-existing Grade 2 or greater peripheral neuropathy.
• History of any grade ≥3 venous thromboembolic event (VTE)
• Patients with clinically significant cardiovascular disease.

Where it is running

• Massey Cancer Center — Richmond, Virginia, United States
• ICO Paul Papin — Angers, France
• CHU Jean Minjoz — Besançon, France
• Institut Bergonié — Bordeaux, France
• Centre François Baclesse — Caen, France
• Centre Oscar Lambret — Lille, France
• Centre Léon Bérard — Lyon, France
• ICM Val d'Aurelle — Montpellier, France
• Hôpital Privé du Confluent S.A.S. — Nantes, France
• Centre Antoine Lacassagne — Nice, France
• Groupe Hospitalier Diaconesses-Croix Saint-Simon — Paris, France
• HEGP — Paris, France
• Centre Hospitalier Lyon Sud — Pierre-Bénite, France
• Centre CARIO-HPCA — Plérin, France
• ICO Centre René Gauducheau — Saint-Herblain, France
• Hôpitaux Universitaires — Strasbourg, France
• Institut Claudius Régaud — Toulouse, France
• Gustave Roussy — Villejuif, France
• Universitätsmedizin Mainz — Mainz, Germany
• Helios-Klinikum Wuppertal — Wuppertal, Germany
• Fondazione Del Piemonte Per L'Oncologia — Candiolo, Italy
• Azienda Ospedaliero-Universitaria Di Ferrara — Ferrara, Italy
• Ospedale Lecce 'Vito Fazzi' — Lecce, Italy
• ASST Lecco — Lecco, Italy
• Willis Knighton Cancer Center — Shreveport, Louisiana, United States

Full record on ClinicalTrials.gov

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