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Neoadjuvant Afatinib in Early Stage Non Small Cell Lung Cancer.

Phase 2
Suspended
Conditions
Non Small Cell Lung Cancer
Interventions
Procedure: Immediate surgery
Registration Number
NCT02470065
Lead Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Brief Summary

This is a multicenter, randomized, 1:1, non-comparative phase II trial. Patients with early stage NSCLC will be randomized between ARM A: neoadjuvant afatinib followed by surgery and ARM B: immediate surgery with curative intent.

Detailed Description

This is a multicenter, prospective, open-label, randomized, non-comparative, two-arm phase II trial aiming to evaluate afatinib treatment in pre-operative setting in patients with EGFR mutated NSCLC.

After signing of the informed consent, patients will be registered and screened for eligibility and upon confirmation of all eligibility criteria, patients will be randomized 1:1 to:

* Arm A: once daily afatinib at a dose of 40 mg for 8 weeks followed by surgery with curative intent (anatomical resection and systematic lymph node dissection).

* Arm B: immediate surgery with curative intent (anatomical resection and systematic lymph node dissection).

Response evaluation in the pre-operative arm will be performed through CT scans at baseline, 4 and 8 weeks.

The first 5 patients enrolled in arm A will be part of a safety run-in to check that afatinib treatment doesn't delay surgery.

Recruitment & Eligibility

Status
SUSPENDED
Sex
All
Target Recruitment
38
Inclusion Criteria

Histological or cytological diagnosis of NSCLC;

  • Patients considered operable and with resectable tumor with curative intent (anatomical resection and systematic lymph node dissection) based on evaluation by a thoracic multi-disciplinary team composed of at least a thoracic surgeon, oncologist and radiologist;
  • Stage I-III (T1a-3, N0-1, M0 according to UICC version 7) NSCLC by local staging criteria potentially treatable by radical (curative) surgery. Patients with T1 tumor at baseline will be limited to 20%;
  • Radiologically measurable disease according to RECIST criteria 1.1; assessed by chest and upper abdomen CT scan within 2 weeks (+1 week) prior to registration); brain CT scan or MRI according to local practice;
  • No prior treatment for NSCLC is allowed;
  • Adequate tissue in terms of quality and quantity for EGFR local testing.
Exclusion Criteria
  • no adequate bone marrow function within 2 weeks prior to randomization
  • no adequate liver function. Patients with Gilbert's syndrome total bilirubin must be below 4 times institutional upper limit of normal; within 2 weeks prior to randomization
  • no adequate renal function within 2 weeks prior to randomization
  • known positivity to human immunodeficiency virus (HIV), hepatitis B or hepatitis C;
  • known history of allergic reactions attributed to compounds of similar chemical or biological composition;
  • history of a hematologic or primary solid tumor malignancy, unless no evidence of that disease for 5 years, except pT1-2 prostatic cancer Gleason score < 6, superficial bladder cancer, non melanoma skin cancer or carcinoma in situ of the cervix;

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Immediate surgeryImmediate surgeryimmediate surgery with curative intent (anatomical resection and systematic lymph node dissection).
Neo adjuvant afatinibImmediate surgeryonce daily afatinib at a dose of 40 mg for 8 weeks followed by surgery with curative intent (anatomical resection and systematic lymph node dissection).
Neo adjuvant afatinibAfatinibonce daily afatinib at a dose of 40 mg for 8 weeks followed by surgery with curative intent (anatomical resection and systematic lymph node dissection).
Primary Outcome Measures
NameTimeMethod
Decrease in cT-stage8 weeks

decrease in cT-stage descriptor measured according to RECIST 1.1

Secondary Outcome Measures
NameTimeMethod
Change in surgical treatment intent and technique8 weeks
Response Rate8 weeks

proportion of patients whose response is either complete response (CR) or partial response (PR) using RECIST 1.1;

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