Association Capmatinib + Spartalizumab dans l'Adénocarcinome Oesogastrique Avancé

Essai clinique

Type : Académique
Statut : Ouvert
Phase : II
Type de traitement : Thérapie ciblée
Date d'ouverture : 22/03/2022
Date clôture : 31/10/2025
Promoteur : Assistance Publique - Hôpitaux de Paris
Progression du cancer: Loco-régional et à distance
Résumé :

Immunotherapy with anti-PD1 antibodies provides encouraging results on a subset of patients. Capmatinib, a MET inhibitor, has shown an imunomodulatory effect and a synergy with spartalizumab a PD-1 inhibitor. The purpose of this phase II trial is to evaluate the efficacy and safety of the combination of capmatinib + spartalizumab in adult patients with advanced oesogastric adenocarcinoma.

Domaines/spécialités :
  • Cancers digestifs
    • Œsophage
    • Estomac
Pathologies :
  • Tumeur maligne de l'oesophage - Cim10 : C15
  • Tumeur maligne de l'estomac - Cim10 : C16
Liens externes :

Critères de population

Sexe : Homme et femme
Age minimum : 18 ans
Critères d’inclusion :
  • Histologically or cytologically documented locally advanced or metastatic oesogastric adenocarcinoma.
  • Unresectable tumor.
  • Patients must have received at least one prior systemic chemotherapy based on platinium salt and fluoropyrimidine with documented progression during chemotherapy.
  • Patients must have received trastuzumab in case of HER2 positive tumor (HER2 +++ or HER2++ and FISH or SISH+)
  • Determination of tumor MET amplification by FISH available
  • ECOG Performance Status ≤ 1.
  • Measurable tumoral disease according to RECIST 1.1 criteria.
  • Patients must be willing and able to swallow and retain oral medication.
  • Age ≥18 years.
  • Women of childbearing potential and males who are sexually active must agree to follow instructions for method(s) of contraception for the duration of study treatments with Capmatinib and Spartalizumab until 7 days after the last dose of Capmatinib and 150 days after the last dose of Spartalizumab
  • Consent to participate in the trial after information
  • Affiliated to a social security system
Critères d’exclusion :
  • Previous treatment with immunotherapy or MET inhibitor
  • Impossibility to take oral medication
  • Persistent toxicities related to prior treatment of grade greater than 1
  • Presence or history of another malignant disease that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
  • Use of any live vaccines within 4 weeks of initiation of study treatment.
  • History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).
  • History or current interstitial lung disease or non-infectious pneumonitis
  • Active autoimmune disease or a documented history of autoimmune disease (Patients with vitiligo, controlled type I diabetes mellitus on stable insulin dose, residual autoimmune-related hypothyroidism only requiring hormone replacement or psoriasis not requiring systemic treatment are permitted).
  • Allogenic bone marrow or solid organ transplant
  • Uncontrolled active infection
  • Human Immunodeficiency Virus (HIV) infection
  • Untreated active Hepatitis B infection (HBsAg positive) (Patients with active hepatitis B (HBsAg positive) may be enrolled provided viral load (HBV DNA) at screening is <100 UI/mL. Patients may receive antiviral treatment with lamivudine, tenofovir, entecavir, or other antiviral agents before the initiation of study treatment to suppress viral replication).
  • Untreated active hepatitis C (HCV RNA positive) (patients that achieved a sustained virological response after antiviral treatment and show absence of detectable HCV RNA ≥6 months after cessation of antiviral treatment are eligible)
  • Untreated or symptomatic central nervous system (CNS) lesion. However, patients are eligible if: a) all known CNS lesions have been treated with radiotherapy or surgery and b) patient remained without evidence of CNS disease progression ≥4 weeks after treatment and c) patients must be off corticosteroid therapy for ≥2 weeks
  • Clinically significant, uncontrolled heart diseases
  • Recent acute coronary syndrome or unstable ischemic heart disease
  • Congestive heart failure ≥ Class III or IV as defined by New York Heart Association
  • Long QT syndrome (> 480 ms in women and 470 ms in men), family history of idiopathic sudden death or congenital long QT syndrome.
  • Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥150 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without antihypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening
  • Surgery less than 4 weeks
  • Radiotherapy less than 2 weeks
  • Pregnancy or breastfeeding or women of child-bearing potential, unless they are using highly effective methods of contraception.
  • Sexually active males unless they use a condom during intercourse while taking capmatinib and for 7 days after stopping treatment and should not father a child in this period.
  • Participants receiving treatment with strong inducers of CYP3A and could not be discontinued ≥ 1 week prior to the start of treatment.
  • Systemic chronic steroid therapy (>10 mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date of first dose of study treatment.
  • Patient having out of range laboratory values defined as:
  • Total bilirubin >2 mg/dL, except for patients with Gilbert's syndrome who are excluded if total bilirubin >3.0 x ULN or direct bilirubin >1.5 x ULN
  • Alanine aminotransferase (ALT) > 3 x ULN
  • Aspartate aminotransferase (AST) > 3 x ULN
  • Coagulation: Prothrombin Time (PT) >4 seconds more than the ULN or International Normalized Ratio (INR) >1.7
  • Absolute neutrophil count (ANC) <1.5 x 109/L
  • Platelet count <75 x 109/L
  • Hemoglobin <9 g/dL
  • Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) <45 mL/min
  • Serum lipase >1 ULN
  • Cardiac troponin I (cTnI) elevation >2 x ULN
  • Potassium, Magnesium, Phosphorus, total Calcium (corrected for serum albumin) outside of normal limits (patients may be enrolled if corrected to within normal limits with supplements during screening)
  • Patients under legal protection
  • Participation to another interventional study with treatment

Centres d'investigation

En cours
Nom : Centre Georges François Leclerc - CGFL
Ville : DIJON (21)
RESPONSABLE MÉDICAL
Aucun responsable médical renseigné
CONTACT TECHNIQUE
Aucun contact technique renseigné
Terminée
Nom : CHU de Besançon
Ville : BESANÇON (25)
RESPONSABLE MÉDICAL
Aucun responsable médical renseigné
CONTACT TECHNIQUE
Aucun contact technique renseigné

Référentiels Oncologik

  • Estomac
  • Adénocarcinome de l'œsophage et de la jonction œsogastrique