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Trial record 1 of 1 for:    NCT03801304
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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03801304
Recruitment Status : Active, not recruiting
First Posted : January 11, 2019
Last Update Posted : August 7, 2020
Sponsor:
Collaborators:
Groupe Français de Pneumo-Cancérologie
Roche Farma, S.A
Pierre Fabre Medicament
Information provided by (Responsible Party):
University Hospital, Brest

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: Atezolizumab Drug: Vinorelbine Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
  • Atezolizumab will be administered of 1200 mg on day 1 of each 21-day cycle with IV infusions .
  • Vinorelbine at the dose of 40 mg per days will be administered on days 1, 3 and 5 of each week of the 21-day cycle.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 24, 2019
Estimated Primary Completion Date : July 24, 2022
Estimated Study Completion Date : July 24, 2023

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Occurrence of death or progression of the disease [ Time Frame: 4 months ]
    To evaluate the occurrence of death or progression of the disease


Secondary Outcome Measures :
  1. Emergence of adverse events (Safety and tolerability) [ Time Frame: 12 months ]
    To evaluate the safety outcomes, tolerability, adverse events frequency

  2. Occurrence of death [ Time Frame: 12 months ]
    To evaluate the occurrence of death over 12 months of follow-up

  3. Objective Response Rate [ Time Frame: 4 months ]
    To evaluate the objective Response Rate and Disease Control Rate

  4. 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).

  5. 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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03801304


Locations
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France
CH Aix en Provence
Aix-en-Provence, France
CHRU de Brest - Hôpital Morvan
Brest, France, 29609
CLCC Caen
Caen, France
CH de Créteil
Créteil, France, 94010
Ch La Roche Sur Yon
La Roche Sur Yon, France, 85000
CHU de Limoges - Hôpital DUPUYTREN
Limoges, France, 87042
CH MEAUX
Meaux, France
CH Pringy
Pringy, France
CH Quimper
Quimper, France
CHU de Rennes
Rennes, France, 35033
CHU Rouen
Rouen, France
CH Saint-Brieuc
Saint-Brieuc, France
Hia Saint Anne
Toulon, France, 83041
Sponsors and Collaborators
University Hospital, Brest
Groupe Français de Pneumo-Cancérologie
Roche Farma, S.A
Pierre Fabre Medicament
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University Hospital, Brest
ClinicalTrials.gov Identifier: NCT03801304    
Other Study ID Numbers: 29BRC18-0005 (VinMetAtezo)
First Posted: January 11, 2019    Key Record Dates
Last Update Posted: August 7, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All collected data that underlie results in a publication
Supporting Materials: Study Protocol
Time Frame: Data will be available beginning three years and ending fifteen years following the final study report completion
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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Brest:
immunotherapy
second line of chemotherapy
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Atezolizumab
Vinorelbine
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action