Trial to Evaluate Safety and Efficacy of Vinorelbine With Metronomic Administration in Combination With Atezolizumab as Second-line Treatment for Patients With Stage IV Non-small Cell Lung Cancer (VinMetAtezo)

June 26, 2026 updated by: University Hospital, Brest

Open Label Phase II Trial to Evaluate Safety and Efficacy of Vinorelbine With Metronomic Administration in Combination With Atezolizumab as Second-line Treatment for Patients With Stage IV Non-small Cell Lung Cancer

The majority of patients diagnosed with advanced NSCLC are treated with platinum-doublet chemotherapy regimens, except those harboring specific oncogenic drivers such as epidermal growth-factor-receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. In the second-line setting, response rates remain low and median survival rarely exceeds 10 months.

Over the past few years, several checkpoint inhibitors targeting programmed cell death protein-1 (PD1) or its ligand (PDL1) used as second-line therapies generated evidence of improving survival and, more recently, as first-line NSCLC treatment.

Although pembrolizumab (anti-PD1) was recently approved as first-line treatment for patients with at least 50% of their NSCLC cells expressing PDL1, many patients are still not benefiting from this first-line agent.

For patients with relapsed NSCLC, atezolizumab (anti-PDL1) prolonged survival compared to docetaxel in the phase II POPLAR and phase III OAK trials. Novel concepts of synergic action between immunotherapy and chemotherapy have emerged recently. However, those types of treatments are given for different durations: chemotherapy is allowed for only a short period (rarely exceeding 6 cycles), while anti-PDL1 can be continued for several months until loss of its clinical benefit.

Metronomic chemotherapy is defined as low-dose and frequent chemotherapy administration, without prolonged drug-free breaks. Metronomic administration of oral vinorelbine has been tested against breast cancer and advanced refractory NSCLC. The combination could have immunostimulatory effects: induction of immunogenic cancer-cell death, enhancement of antigen presentation through dendritic cell modulation, increased cancer-cell immunogenicity, preferential depletion of regulatory T cells, modulation of myeloid-derived suppressor cells, enhancement of the cytotoxic activity of immune-effector cells.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
    • France
      • Aix-en-Provence, France, France
        • CH Aix en Provence
      • Brest, France, France, 29609
        • CHRU de Brest - Hopital Morvan
      • Caen, France, France
        • CLCC Caen
      • Créteil, France, France, 94010
        • CH de Créteil
      • La Roche-sur-Yon, France, France, 85000
        • CH La Roche Sur Yon
      • Limoges, France, France, 87042
        • CHU de Limoges - Hopital Dupuytren
      • Meaux, France, France
        • CH Meaux
      • Pringy, France, France
        • CH Pringy
      • Quimper, France, France
        • Ch Quimper
      • Rennes, France, France, 35033
        • CHU de Rennes
      • Rouen, France, France
        • CHU Rouen
      • Saint-Brieuc, France, France
        • CH Saint-Brieuc
      • Toulon, France, France, 83041
        • Hia Saint Anne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically confirmed NSCLC;
  • Locally advanced and/or metastatic stage IV NSCLC (according to American Joint Committee on Cancers) or recurrent NSCLC);
  • Patients without activating EGFR mutation or ALK rearrangement and ROS1 fusions.
  • Subject has provided a formalin-fixed tumor-tissue sample of a tumor-lesion biopsy, either at the time of or after metastatic disease was diagnosed AND from a site not previously irradiated to assess for PDL1 status. Archived tissue may be acceptable or PDL1 status known;
  • Progressive disease after first-line platinum-doublet-based chemotherapy according to RECIST V.1.1 with measurable lesion (RECIST V1.1);
  • Age ≥18 years, either sex;
  • Eastern Collaborative Oncology Group Performance status (ECOG PS) 0, 1 or 2;
  • Life expectancy exceeds 12 weeks;
  • No history of other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or basal cell or spinocellular carcinoma of the skin;
  • Adequate organ function, demonstrated by the following laboratory results within 3 weeks prior to teatment: Normal hepatic function: bilirubin <1.5 × normal (N), Alanine aminotransferase and Aspartate aminotransferase <2.5 × N or <5 × N if liver metastasis is present;
  • Normal renal function (calculated creatinine clearance ≥45 mL/min);
  • Normal calcemia;
  • Normal hematological function (polynuclear neutrophils >1.5 G/L, platelets >100 G/L and hemoglobin>8g/dl);
  • Women of child-bearing potential must use effective contraception;
  • Men might be surgically sterile or accept to use an effective contraceptive procedure during and until 6 months after the treatment;
  • Written informed consent to participate in the study
  • Patient with social insurance

Exclusion Criteria:

  • ECOG PS >2;
  • Known hypersensitivity to immunotherapy;
  • Small-cell lung cancer, bronchioloalveolar cancer, neuroendocrine cancer;
  • Tumor harbors EGFR-sensitizing (activating) mutations or ALK translocations or ROS1 fusions and that justify treatment with targeted therapy ;
  • Chemotherapy, hormonotherapy, immunotherapy or tyrosine-kinase inhibitors within the past 4 weeks prior to treatment with the trial drug;
  • Radiotherapy (except bone or brain) within the past 3 months prior to baseline imaging;
  • Medical contraindication to oral vinorelbine;
  • Persistence of clinical adverse events with a grade > 2 related to prior treatment;
  • Active brain metastases (e.g. stable for <4 weeks, no adequate previous radiotherapy, symptomatic, requiring anticonvulsants or corticosteroids)
  • Concurrent radiotherapy, except for palliative bone irradiation.
  • Other concurrent severe illnesses (congestive heart failure, unstable angina, significant arrhythmia or myocardial infarction <12 months before study entry);
  • Active or prior documented autoimmune or inflammatory disorders;
  • Active B hepatitis, HIV infection …;
  • Psychiatric or neurological disorders preventing the patient from understanding the nature of the trial;
  • Grade-3 peripheral neuropathy;
  • Uncontrolled infection;
  • Interstitial lung disease or pneumonitis requiring steroid management;
  • Corticosteroid therapy exceeding 10 mg/day;
  • Other severe organic disorders not allowing inclusion in the trial;
  • Malabsorption syndrome;
  • Pregnancy or breast-feeding;
  • Follow-up not possible; and incarcerated or institutionalized patients.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Atezolizumab associated with vinorelbine
  • Atezolizumab will be administered with IV infusions. The first one will be a 60-min IV infusion; the subsequent infusions will last 30 minutes when well-tolerated at the dose of 1200 mg on day 1 of each 21-day cycle.
  • Vinorelbine capsules are taken orally on days 1, 3 and 5 of each week of the 21-day cycle. Vinorelbine will be administered at the dose of 40 mg per day on days 1, 3 and 5 of each week of the 21-day cycle. In case of toxicity, the dose will be decreased to 30 mg.
Drug: Atezolizumab
Atezolizumab in IV infusions
Drug: Vinorelbine
Vinorelbine capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of death or progression of the disease
Time Frame: 4 months
To evaluate the occurrence of death or progression of the disease
4 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Emergence of adverse events (Safety and tolerability)
Time Frame: 12 months
To evaluate the safety outcomes, tolerability, adverse events frequency
12 months
Occurrence of death
Time Frame: 12 months
To evaluate the occurrence of death over 12 months of follow-up
12 months
Objective Response Rate
Time Frame: 4 months
To evaluate the objective Response Rate and Disease Control Rate
4 months
Following of the quality of life
Time Frame: 12 months
The scale EuroQol 5 dimensions (EDQ5) is used to evaluate the quality of life. The EQ-5D scale is a standardised measure of health status to provide a simple, generic measure of health for clinical and economic appraisal, whih is divided by the EQ-5D descriptive system (mobility, self care, usual activities, pain/discomfort, anxiety/depression) and the EQ Visual Analogue scale (EQ VAS). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, and extreme problems).
12 months
Following of the quality of life
Time Frame: 12 months
The EORTC QLQ-C30 is a questionnaire with 30 questions developed to assess the quality of life of cancer patients. An essential aspect of the "modular" approach to QOL assessment adopted by the EORTC Quality of Life Group is the development of modules specific to tumour site, treatment modality, or a QOL dimension, to be administered in addition to the core questionnaire (EORTC QLQ-C30).
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Brest

Collaborators

Roche Farma, S.A
Pierre Fabre Medicament
Groupe Francais De Pneumo-Cancerologie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 24, 2019

Primary Completion (Actual)

January 4, 2021

Study Completion (Actual)

February 23, 2022

Study Registration Dates

First Submitted

January 7, 2019

First Submitted That Met QC Criteria

January 10, 2019

First Posted (Actual)

January 11, 2019

Study Record Updates

Last Update Posted (Actual)

June 30, 2026

Last Update Submitted That Met QC Criteria

June 26, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 29BRC18-0005 (VinMetAtezo)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All collected data that underlie results in a publication

IPD Sharing Time Frame

Data will be available beginning three years and ending fifteen years following the final study report completion

IPD Sharing Access Criteria

Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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