Afatinib in NSCLC With HER2 Mutation

NCT02369484 | Completed Phase 2 Results DMC

• 4 other identifiers: ETOP 7-142014-005098-351200.230SNCTP000001674
• Study Type: interventional
• Target: 13
• Locations: 4 countries
• Sites: 5

Brief Summary

The purpose of this study is to investigate the control of disease in pretreated patients with advanced non small cell lung cancer (NSCLC) harbouring HER2 exon 20 mutations as well as the safety and tolerability (how severe the side effects are) of the treatment with afatinib.

Conditions

NSCLC

Keywords

Stage IIIb/ IV NSCLC harbouring HER2 exon 20 mutations

Outcome Measures

Primary Outcomes (1)

• Disease Control (Defined as Complete or Partial Response, or Disease Stabilisation Lasting at Least 12 Weeks)

  Disease control (DC) is defined as complete or partial response, or disease stabilisation lasting at least 12 weeks. Disease control will be determined using RECIST 1.1 criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. Progression (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum recorded on the trial. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions denotes disease progression. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters recorded on the trial.

  at interim (after the first 9 pts have been followed for 12 weeks) & final analysis (approx. 40 months after inclusion of first pt)

Secondary Outcomes (4)

• Progression-free Survival

  Time assessed from the date of enrolment until documented progression or death (max 36 months)

• Objective Response

  Assessed across all time-points during the period from enrolment to termination of trial treatment (max. 36 months)

• Overall Survival

  Time assessed from the date of enrolment until death (max 36 months)

• Toxicities of Treatment

  Assessed from the date of informed consent until 90 days after the final dose of afatinib (max 18 months).

Study Arms (1)

Afatinib

OTHER

Afatinib 40 mg p.o./day until tumour progression or lack of tolerability

Drug: Afatinib

Interventions

Afatinib DRUG

40mg p.o./ day until documented progression or unacceptable toxicity

Also known as: Giotrif, BIBW 2992

Afatinib

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed non small cell lung cancer
• Stage IIIB (non amenable to curative-intent multimodal treatment) or IV NSCLC, according to 7th TNM classification.
• Contrast-enhanced CT of thorax and upper abdomen (incl. liver, kidney, adrenals);
• brain MRI or CT within 28 days before the date of enrolment.
• Non-predominant squamous subtype (\<50% squamous cells).
• Previous treatment with a platinum based chemotherapy for advanced disease; or Disease relapse or progression within \<6 months after adjuvant platinum based chemotherapy, or (definitive) platinum-based chemo(radio)therapy for stage I-III NSCLC
• Measurable or evaluable disease (according to RECIST 1.1 criteria). Not eligible: patients with only one measurable or evaluable tumour lesion which was resected or irradiated prior to enrolment.
• Locally documented HER2 mutation
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Life expectancy \>3 months.
• Adequate haematological function:
• WBC ≥ 2000/μL
• haemoglobin ≥ 9 g/dL
• neutrophils count ≥1.5×109/L

You may not qualify if:

• Patient with mixed small-cell and non-small-cell histologic features
• Uncontrolled lepto-meningeal metastatic disease. Radiotherapy-treated or asymptomatic brain metastases are allowed (no systematic screening). Patients with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids or have been on stable dose of corticosteroids for at least 4 weeks before starting trial treatment. Any symptoms attributed to brain metastases must be stable for at least 4 weeks before date of enrolment.
• Previous treatment with HER2 targeted antibody or tyrosine kinase inhibitor including afatinib.
• Major surgery within 4 weeks before starting trial treatment or scheduled for surgery during the projected course of the trial.
• Patient who has had in the past 3 years any previous or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ ductal carcinoma of the breast.
• History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of III or IV (see Table 2 below), unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior to enrolment.
• Patient with other serious diseases or clinical conditions, including but not limited to uncontrolled active infection and any other serious underlying medical processes that could affect the patient's capacity to participate in the trial.
• Known HIV, active Hepatitis B or Hepatitis C infection (screening not required).
• Known or suspected hypersensitivity to afatinib or any of its excipients.
• Interstitial lung disease or pulmonary fibrosis.
• Women who are pregnant or in the period of lactation.
• Patients with any concurrent systemic anticancer therapy.
• Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the trial drug (e.g. Crohn's disease, ulcerative colitis, chronic diarrhea, malabsorption.
• Patient who received treatment with an investigational drug agent during the 3 weeks before enrolment in the trial.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead

Study Sites (5)

Universitätsklinikum Köln

Cologne, Germany

Location

NKI-AVL

Amsterdam, Netherlands

Location

Vall d'Hebron University Hospital

Barcelona, Spain

Location

CHUV

Lausanne, Switzerland

Location

USZ

Zurich, Switzerland

Location

Related Publications (3)

• Mazieres J, Peters S, Lepage B, Cortot AB, Barlesi F, Beau-Faller M, Besse B, Blons H, Mansuet-Lupo A, Urban T, Moro-Sibilot D, Dansin E, Chouaid C, Wislez M, Diebold J, Felip E, Rouquette I, Milia JD, Gautschi O. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol. 2013 Jun 1;31(16):1997-2003. doi: 10.1200/JCO.2012.45.6095. Epub 2013 Apr 22.

  PMID: 23610105 BACKGROUND

• De Greve J, Teugels E, Geers C, Decoster L, Galdermans D, De Mey J, Everaert H, Umelo I, In't Veld P, Schallier D. Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu. Lung Cancer. 2012 Apr;76(1):123-7. doi: 10.1016/j.lungcan.2012.01.008. Epub 2012 Feb 10.

  PMID: 22325357 BACKGROUND

• Tomizawa K, Suda K, Onozato R, Kosaka T, Endoh H, Sekido Y, Shigematsu H, Kuwano H, Yatabe Y, Mitsudomi T. Prognostic and predictive implications of HER2/ERBB2/neu gene mutations in lung cancers. Lung Cancer. 2011 Oct;74(1):139-44. doi: 10.1016/j.lungcan.2011.01.014. Epub 2011 Feb 25.

  PMID: 21353324 BACKGROUND

Related Links

• Sponsor

MeSH Terms

Interventions

Afatinib

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Heidi Roschitzki-Voser, Lead Trial Activities
• Organization: European Thoracic Oncology Platform (ETOP)

Heidi.Roschitzki@etop-eu.org

+41 31 511 94 18

Study Officials

• Solange Peters, MD-PhD

  Centre Hospitalier Universitaire Vaudois (CHUV); Lausanne, Switzerland

  STUDY CHAIR

• Rafal Dziadziuszko, MD

  Medical University of Gdansk, Gdansk, Poland

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: February 17, 2015
• First Posted: February 24, 2015
• Study Start: September 16, 2015
• Primary Completion: September 15, 2017
• Study Completion: September 15, 2017
• Last Updated: August 24, 2022
• Results First Posted: March 1, 2019

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); CH (2); ES (1); DE (1)