Etude : VINMETATEZO /



ATTENTION : pour chaque essai clinique, les éléments affichés ci-dessous ne sont pas exhaustifs, et le protocole fourni par le promoteur reste l’unique document à consulter pour mener à bien un essai clinique sur centre. Pour plus d'informations, contactez le référent du territoire concerné.


Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : VINMETATEZO

Nom :

Traitement : Métastasique ou localement avancé

Type d'étude : Ciblage moléculaire / Innovation thérapeutique

Dernière MÀJ : 05/08/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Phase II ouverte dont l’objectif est d’évaluer la tolérance et l’efficacité de la vinorelbine métronomique en combinaison avec l’atezolizumab comme deuxième ligne de traitement des patients porteurs de cancer pulmonaire métastatique non à petites cellules

Spécialité : Organes respiratoires et intrathoraciques
Localisation : C34 - Tumeur maligne des bronches et du poumon
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : 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.

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.

Phase : II

Stade : III à IV

2
Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - 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

Critères de non-inclusion : - 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.
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03801304
Promoteur :
CHU de Brest
Type de sponsor : Institutionnel
2 avenue Foch
29200 BREST

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre François BACLESSE - 3 avenue du Général Harris - 14000 CAEN

Investigateur :
Radj GERVAIS

TEC / ARC / IDE :
Karim HAMOND
k.hamond@
baclesse.unicancer.fr

Ouverture de l'essai : OUVERT

MAJ : 05/08/2019