- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT02488694
Maintaining ERBB Blockade in EGFR-mutated Lung Cancer (MARBLE)
A Randomized, Open-label, Phase II Study of Maintaining Pan-ERBB Blockade Following Platinum-based Induction Chemotherapy in Patients With EGFR Mutated, Metastatic Non-small-cell Lung Cancer Progressing After Treatment With Afatinib as First EGFR-targeting Agent
Aperçu de l'étude
Statut
Intervention / Traitement
Description détaillée
This is a randomized, open-label, phase II study of maintaining pan-ERBB blockade following platinum-based induction chemotherapy in patients with EGFR mutated, metastatic NSCLC progressing after first-line treatment with afatinib.
Patients who have progressed after first-line treatment with afatinib will be screened while receiving an induction phase which consists of at least three but not more than four cycles of cisplatin/carboplatin plus pemetrexed given in 21-day cycles. Patients who do not progress (i.e. complete or partial response, or stable disease - CR, PR or SD) after completion of three or four cycles induction chemotherapy will then be randomized (1:1 ratio) to receive maintenance therapy with either afatinib (40 mg/d, or last dose if reduced during first-line treatment) or pemetrexed (500 mg/m² every 21 days, or 375 mg/m² if dose was reduced during induction therapy) until disease progression, unacceptable toxicity or patient consent withdrawal.
Type d'étude
Inscription (Réel)
Phase
- Phase 2
Contacts et emplacements
Lieux d'étude
-
-
-
Essen, Allemagne
- Universitätsklinikum Essen
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Histologically or cytologically confirmed diagnosis of non-small-cell lung cancer (NSCLC) with no curative therapeutic option. Patients with Stage IV (UICC 7th edition) disease or Stage IIIB disease not amenable to curative intent surgery or radiotherapy are enrolled. Patients with mixed histology are eligible if NSCLC is the predominant histology
- Documented somatic EGFR mutation as determined by medically accepted assay technology
- Patients with documented progression after response (CR/PR) or stable disease (SD) for at least 6 months of treatment with afatinib as first tyrosine kinase inhibitor (either given as first-line therapy or being switched to afatinib after up to 4 courses of platinum-based chemotherapy)
- Patients who have completed 3 or 4 cycles of cisplatin or carboplatin plus pemetrexed induction chemotherapy prior to randomization leading to documented response (CR/PR) or SD according to RECIST 1.1
- At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Male or female patient with age ≥18 years
- ECOG performance status ≤ 2
Adequate organ and bone marrow function, defined as all of the following:
Before the last cycle of induction chemotherapy or after hematopoietic recovery from the last cycle of induction chemotherapy:
- Absolute neutrophil count (ANC) ≥ 1,500 / mm3
- Platelet count ≥ 100,000 / mm3
- Creatinine clearance ≥ 45 ml / min (calculated according to Cockroft and Gault, or Tc99m-DPTA clearance or similar methodology). Patients with creatinine clearance of 45 to 79 ml/min should refrain from using NSAID at least 2 days before and 2 days after infusion of pemetrexed. Long-acting NSAID should be terminated 5 days before pemetrexed infusion.
- Total serum bilirubin ≤ 1.5 times upper limit of institutional normal (ULN)
- Serum aspartate amino transferase (AST) and serum alanine amino transferase (ALT) ≤ 3 times the upper limit of institutional normal (ULN) ( ≤ 5 times ULN if liver function abnormalities are due to underlying malignancy)
- Recovered from any previous therapy related toxicity to ≤ Grade 1 at study entry (except for stable sensory neuropathy ≤ Grade 2 and alopecia)
- Written informed consent
- Ability to comply with the protocol for the duration of the study, including hospital/office visits for treatment and scheduled follow-up visits and examinations
Exclusion Criteria:
- Systemic therapy for metastatic disease or relapse other than (a) first-line therapy with afatinib or (b) afatinib given as first EGFR-targeting agent following up to 4 courses of platinum-based chemotherapy with no disease progression between first-line chemotherapy and initiation of afatinib (prior adjuvant chemotherapy is allowed) and 3 to 4 cycles of induction chemotherapy with cisplatin or carboplatin and pemetrexed following afatinib failure
- Prior treatment with erlotinib, gefitinib or other investigational or approved EGFR-targeting small molecules or antibodies
- Known EGFR T790M mutation (analysis not mandatory)
- Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study
Extended radiotherapy within 4 weeks prior to randomization, except as follows:
- Palliative, limited local radiation to non-target lesions (e.g. isolated bone metastases) may be allowed up to 2 weeks prior to randomization, and
- single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with sponsor prior to enrolling
Active brain metastases except for the followings:
- Asymptomatic brain metastases incidentally found during screening process which do not require local treatment in the opinion of the investigator.
- Asymptomatic brain metastases for which local treatment has been given: stable for at least 4 weeks of lower dose corticosteroids (e.g., dexamethasone up to 4 mg/d) and/or non-enzyme-inducing anti-convulsants treatment before study randomization.
- Brain metastases controlled after surgery and/or radiotherapy
- Meningeal carcinomatosis
- Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, non-invasive bladder cancer, ductal carcinoma in situ of the breast, or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured. Definitively treated localized low/intermediate risk prostate cancer (Gleason score ≤ 7) is allowed when a rise in serum PSA level by ≥ 2 ng/mL above the nadir is excluded
- Known pre-existing interstitial lung disease
- Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug in the opinion of the investigator (e.g. Crohn's Disease, ulcerative colitis, chronic diarrhea, and malabsorption)
- Clinically relevant cardiovascular abnormalities as judged by the investigator such as uncontrolled hypertension, congestive heart failure ≥ NYHA grade III, unstable angina or myocardial infarction within the past 6 months, or poorly controlled cardiac arrhythmia in the opinion of investigator
- Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug, or renders the patient at high risk of treatment complications
- Women of child-bearing potential and men who are able to father a child, unwilling to be abstinent or use adequate contraception prior to study entry, for the duration of study participation and for at least 2 weeks after treatment has ended
- Female patient pregnant or breast-feeding
- Known active infection with HBV, HCV or HIV
- Any contraindications for therapy with pemetrexed
- Known hypersensitivity to afatinib or the excipients of any of the trial drugs
- Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 60 days prior to treatment start
- Pleurocentesis or paracentesis should be considered in patients with clinically significant pleural effusions or ascites if clinically indicated. However, per SmPC of pemetrexed the presence of effusion is not an exclusion criteria
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
---|---|
Expérimental: Arm A: Afatinib
105 patients to be treated with afatinib
|
40 mg/d
Autres noms:
|
Comparateur actif: Arm B: Pemetrexed
105 patients to be treated with pemetrexed
|
500 mg/m² i.v. on d1 of each 21-day cycle
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Progression-free survival
Délai: 40 months
|
The primary endpoint of this study is progression-free survival (RECIST 1.1).
|
40 months
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Overall survival
Délai: 40 months
|
Efficacy measure
|
40 months
|
Objective response rate
Délai: 40 months
|
Objective response rate (ORR), clinical benefit rate (RECIST 1.1); Efficacy measure
|
40 months
|
Quality of Life
Délai: 40 month
|
Health-Related Quality of Life (HRQoL)
|
40 month
|
Safety (intensity and incidence of adverse events, graded according to US NCI CTCAE Version 4.03)
Délai: 40 month
|
Safety, toxicity (intensity and incidence of adverse events, graded according to US NCI CTCAE Version 4.03)
|
40 month
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Martin Schuler, Prof. Dr., Westdeutsches Tumorzentrum, Universitätsklinikum Essen
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies des voies respiratoires
- Tumeurs
- Maladies pulmonaires
- Tumeurs par site
- Tumeurs des voies respiratoires
- Tumeurs thoraciques
- Carcinome bronchique
- Tumeurs bronchiques
- Tumeurs pulmonaires
- Carcinome pulmonaire non à petites cellules
- Mécanismes moléculaires de l'action pharmacologique
- Inhibiteurs de la synthèse des acides nucléiques
- Inhibiteurs d'enzymes
- Agents antinéoplasiques
- Inhibiteurs de protéine kinase
- Antagonistes de l'acide folique
- Pémétrexed
- Afatinib
Autres numéros d'identification d'étude
- AIO-TRK-0114
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
Essais cliniques sur Afatinib
-
Boehringer IngelheimComplété
-
Boehringer IngelheimComplétéCarcinome pulmonaire non à petites cellulesGrèce
-
Boehringer IngelheimComplétéTumeurs neuroectodermiques | RhabdomyosarcomeÉtats-Unis, Espagne, Canada, Allemagne, Italie, Royaume-Uni, Australie, L'Autriche, Danemark, Îles Féroé, France, Pays-Bas
-
Boehringer IngelheimApprouvé pour la commercialisation
-
Boehringer IngelheimComplétéCancer du poumon non épidermoïde et non à petites cellulesJapon
-
Boehringer IngelheimPlus disponible
-
Boehringer IngelheimComplétéCarcinome pulmonaire non à petites cellulesCorée, République de
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)RésiliéCarcinome épidermoïde de la tête et du couÉtats-Unis
-
Medical University of South CarolinaBoehringer IngelheimRetiré