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

NCT03801304 | Completed Phase 2 DMC

• 1 other identifier: 29BRC18-0005 (VinMetAtezo)
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 13

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.

Conditions

Non-small Cell Lung Cancer

Keywords

immunotherapy; second line of chemotherapy

Outcome Measures

Primary Outcomes (1)

• Occurrence of death or progression of the disease

  To evaluate the occurrence of death or progression of the disease

  4 months

Secondary Outcomes (5)

• Emergence of adverse events (Safety and tolerability)

  12 months

• Occurrence of death

  12 months

• Objective Response Rate

  4 months

• Following of the quality of life

  12 months

• Following of the quality of life

  12 months

Study Arms (1)

Atezolizumab associated with vinorelbine

EXPERIMENTAL

* 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; Drug: Vinorelbine

Interventions

Atezolizumab DRUG

Atezolizumab in IV infusions

Atezolizumab associated with vinorelbine

Vinorelbine DRUG

Vinorelbine capsules

Atezolizumab associated with vinorelbine

Eligibility Criteria

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

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• University Hospital, Brest: lead
• Groupe Francais De Pneumo-Cancerologie: collaborator
• Roche Farma, S.A: collaborator
• Pierre Fabre Medicament: collaborator

Study Sites (13)

CH Aix en Provence

Aix-en-Provence, France

Location

CHRU de Brest - Hôpital Morvan

Brest, 29609, France

Location

CLCC Caen

Caen, France

Location

CH de Créteil

Créteil, 94010, France

Location

Ch La Roche Sur Yon

La Roche-sur-Yon, 85000, France

Location

CHU de Limoges - Hôpital DUPUYTREN

Limoges, 87042, France

Location

CH MEAUX

Meaux, France

Location

CH Pringy

Pringy, France

Location

CH Quimper

Quimper, France

Location

CHU de Rennes

Rennes, 35033, France

Location

CHU Rouen

Rouen, France

Location

CH Saint-Brieuc

Saint-Brieuc, France

Location

Hia Saint Anne

Toulon, 83041, France

Location

Related Publications (1)

• Vergnenegre A, Monnet I, Bizieux A, Bernardi M, Chiapa AM, Lena H, Chouaid C, Robinet G. Open-label Phase II trial to evaluate safety and efficacy of second-line metronomic oral vinorelbine-atezolizumab combination for stage-IV non-small-cell lung cancer - VinMetAtezo trial, (GFPCdouble dagger 04-2017). Future Oncol. 2020 Feb;16(4):5-10. doi: 10.2217/fon-2019-0730. Epub 2020 Jan 2.

  PMID: 31894704 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab; Vinorelbine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: * 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.

Study Record Dates

• First Submitted: January 7, 2019
• First Posted: January 11, 2019
• Study Start: January 24, 2019
• Primary Completion: January 4, 2021
• Study Completion: February 23, 2022
• Last Updated: May 12, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: 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.

Locations

FR (13)