Study of Osimertinib in Patients with a Lung Cancer with Brain or Leptomeningeal Metastases with EGFR Mutation

NCT04233021 | Completed Phase 2

• 1 other identifier: IFCT-1804
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 36

Brief Summary

Treatment of non-small cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) mutation is mainly based on tyrosine kinase inhibitors (TKIs) targeting EGFR. 1st or 2nd generation inhibitors have been shown to be superior to chemotherapy in terms of Progression-Free Survival (PFS) when used as 1st line treatment. In case of progression at several metastatic sites, systemic treatment will be considered and will depend on the presence of the TKI resistance mutation, the T790M mutation. In the presence of the T790M mutation, osimertinib is superior to chemotherapy in terms of progression-free survival, while in the absence of the T790M mutation, platinum salt chemotherapy is recommended. In case of local progression, treatment of the site in progression by radiotherapy and/or surgery is considered. As these local treatments can cause long-term adverse effects, systemic treatments are increasingly being considered in this indication. Brain and leptomeningeal metastases are the most frequent isolated site of progression in EGFR mutated patients treated with TKI. The high frequency of isolated cerebral and leptomeningeal progression is a consequence of the lower diffusion of 1st and 2nd generation TKIs in the central nervous system (CNS). Osimertinib is a 3rd generation TKI that has the particularity of overcoming the T790M mutation and having greater brain penetration than 1st or 2nd generation TKIs, which could make it an attractive therapeutic option in the event of brain progression or leptomeningeal progression. However, its efficacy in patients with cerebral or leptomeningeal metastases is still poorly understood.

Conditions

Non Small Cell Lung Cancer Metastatic; Leptomeningeal Metastasis; Brain Metastases; EGFR Activating Mutation

Keywords

IFCT; NSCLC; EGFR

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Objective Response Rate at 6 months using EANO-ESMO criteria (cohort 1) and RECIST1.1 criteria (cohorts 2)

  6 months

Secondary Outcomes (7)

• Overall Survival

  About 24 months

• Progression-free survival

  About 24 months

• CNS Progression-free survival

  About 24 months

• Incidence, type and severity of adverse event

  From time of informed consent through treatment period and up to 30 days post last dose of study treatment (about 24 months)

• Evaluate the Quality of life

  From time of randomisation through treatment period (about 24 months)

Study Arms (1)

Osimertinib

EXPERIMENTAL

Osimertinib 80 mg/d

Drug: Osimertinib

Interventions

Osimertinib DRUG

Osimertinib 80 mg/d

Osimertinib

Eligibility Criteria

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

You may qualify if:

• Patient with NSCLC (histological or cytological diagnosis) stage IV (8th UICC TNM edition, 2017).
• Patients with brain and/or leptomeningeal metastases. For cohort 1, the diagnosis of leptomeningeal metastasis requires either 1) detection of cancer cell or EGFR mutation in the CSF, or 2) presence of both clinical and neuro-imaging findings typical of LM, according to EANO-ESMO criteria.
• For Cohort 1, patients could have been previously treated with maximum 3 lines of anti-cancer treatment.
• For cohort 2, patients could have been previously treated with maximum 1 line of anti-cancer treatment.
• In case of previous chemotherapy, a wash-out period of 28 days will be applied. If there was any prior therapy with an investigational agent, a washout period of five half-lives of the compound or 3 months, whichever is greater, is needed.
• Patient having recovered from all grade ≤ 1 toxicities related to previous anticancer therapies (CTCAE v 5.0) except for alopecia, platinum-therapy-related neuropathy (where ≤2 is allowed).
• \. Presence of at least one evaluable lesion not previously irradiated according to RECIST 1.1. For cohort 2, presence of one CNS evaluable lesion not previously irradiated according to RECIST 1.1.The radiological assessment has to be done within the timelines indicated.
• \. Age of at least 18 years old. 10. Performance status (PS) 0 to 2 (ECOG) except for patients with leptomeningeal carcinomatosis (cohort 1) a PS 3 is authorised.
• \. Patient with a life expectancy of ≥ 6 weeks for cohort 1 and ≥ 12 weeks for cohort 2.
• \. Haematological function:
• Absolute number of neutrophils ≥ 1.5 x 109/L;
• Platelets ≥ 100 x 109/L;
• Haemoglobin ≥ 9 g/dL (transfusions to maintain or exceed this value are accepted).
• \. Hepatic function:
• Total bilirubin ≤ 1.5 x UNL (Upper Normal Limit) or ≤ 3 x UNL in case of documented Gilbert's syndrome or liver metastases;

You may not qualify if:

• Small cell lung cancer histology (SCLC) or tumours with mixt histology including a SCLC component.
• Previous treatment with osimertinib or another 3rd generation EGFR inhibitor.
• Previous treatment with any EGFR TKI (cohort 2 only)
• Brain progression requiring whole brain radiation without delay.
• Local treatments (neurosurgical or stereotactic treatment) for brain metastases performed less than 2 weeks prior to enrolment.
• Local brain treatment scheduled during study treatment.
• Patient who received radiotherapy including the lung fields ≤ 4 weeks before enrolment or patient who has not recovered from radiotherapy-induced toxicities. For all other body sites (including radiotherapy on thoracic vertebrae and ribs), radiotherapy ≤ 2 weeks before enrolment or who have not recovered from radiotherapy-induced toxicities. Palliative radiotherapy for bone lesions ≤ 2 weeks before enrolment is authorised.
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc) \> 470 msec using the screening clinic ECG machine derived QTc value
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block and second degree heart block).
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: Serum/plasma potassium \< LLN; Serum/plasma magnesium \< LLN; Serum/plasma calcium \< LLN), congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes.
• Active malignant disease other than NSCLC.
• Previous or active cancer within the previous 3 years (except for treated carcinoma in situ of the cervix or basal cell skin cancer).
• Others on-going anti-cancer treatment (including hormone therapy).
• Major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic) during the 4 weeks before enrolment or patient who has not recovered from the side effects of such as procedure.

Sponsors & Collaborators

• Intergroupe Francophone de Cancerologie Thoracique: lead

Study Sites (36)

Centre Hospitalier Aix-Pertuis

Aix-en-Provence, 13616, France

Location

CHU Amiens - Groupe Hospitalier Sud

Amiens, 80054, France

Location

Centre Paul Papin

Angers, 49055, France

Location

Hôpital privé d'Antony

Antony, 92166, France

Location

Institut Sainte Catherine

Avignon, 84918, France

Location

Centre Hospitalier de la Côte Basque

Bayonne, 64100, France

Location

CHU Besançon - Hôpital J. MINJOZ

Besançon, 25030, France

Location

Groupe Hospitalier Saint André

Bordeaux, 33075, France

Location

AP-HP Hôpital Ambroise Paré

Boulogne, 92104, France

Location

CHU Côte de Nacre

Caen, 14000, France

Location

Hôpital Louis Pasteur

Colmar, 68024, France

Location

Centre Hospitalier Intercommunal de Créteil

Créteil, 94000, France

Location

CHU Hôpital du Bocage

Dijon, 21079, France

Location

Chu Grenoble

Grenoble, 38043, France

Location

Centre Hospitalier Général

Le Mans, 72037, France

Location

Hôpital Calmette

Lille, 59037, France

Location

CHU Dupuytren

Limoges, 87042, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

Marseille Hôpital Nord

Marseille, 13915, France

Location

CHU Montpellier

Montpellier, 34295, France

Location

Centre Hospitalier Régional - Hôpital de la Source

Orléans, 45000, France

Location

AP-HP Hôpital Cochin

Paris, 75014, France

Location

AP-HP Hôpital Bichat

Paris, 75877, France

Location

Centre Hospitalier Général - Pau

Pau, 64000, France

Location

Lyon - URCOT Centre Hospitalier Universitaire

Pierre-Bénite, 69310, France

Location

CHU de la Réunion - Site Felix Guyon

Saint-Denis, 97400, France

Location

Institut de Cancérologie de l'Ouest - René Gauducheau

Saint-Herblain, 44805, France

Location

CHU de La Réunion-Site Sud

Saint-Pierre, 97448, France

Location

Nouvel Hôpital Civil - Hôpitaux Universitaires de Strasbourg

Strasbourg, 67091, France

Location

Hôpital Foch

Suresnes, 92151, France

Location

HIA Sainte-Anne

Toulon, 83800, France

Location

Hôpital Larrey

Toulouse, 31059, France

Location

CHU Bretonneau

Tours, 37044, France

Location

Valenciennes Clinique PRIV

Valenciennes, 59300, France

Location

Centre Hospitalier de Villefranche-sur-Saône

Villefranche-sur-Saône, 69655, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Related Links

• IFCT Website

MeSH Terms

Conditions

Meningeal Carcinomatosis; Brain Neoplasms

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Brain Diseases; Central Nervous System Diseases

Study Officials

• David PLANCHARD

  Intergroupe Francophone de Cancerologie Thoracique

  PRINCIPAL INVESTIGATOR

• Franck MORIN

  Intergroupe Francophone de Cancerologie Thoracique

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: January 7, 2020
• First Posted: January 18, 2020
• Study Start: July 16, 2020
• Primary Completion: March 15, 2023
• Study Completion: December 27, 2024
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

FR (36)