Induction Therapy With Intercalated Tyrosine Kinase Inhibitor (TKI) and Chemotherapy in NSCLC With Activating Epidermal Growth Factor Receptor (EGFR) Mutation in Stages II-IIIB (NeoIntercal)

This is an interventional treatment trial for Non-squamous Non-small Cell Lung Cancer Stage II focused on measuring induction therapy, NSCLC, Non-small Cell Lung Cancer, curative surgery Read More

Inclusion Criteria:

1. Patients with histologically or cytologically confirmed non-squamous non-small-cell lung cancer (NSCLC) stage II, IIIA and IIIB detected preoperatively by adequate methods and activating EGFR mutation in exons 18-21 and deemed to be able to undergo curative surgery after induction therapy. Stage should be confirmed by PET-CT as well as adequate mediastinal staging. MRI of the brain to exclude CNS metastases is mandatory.
2. At least one unidimensionally measurable lesion meeting RECIST criteria (version 1.1);
3. Performance status of 0 to 1 on the ECOG scale;
4. Estimated life expectancy of at least 12 weeks;
5. Patients aged ≥ 18 years;

6. Adequate organ function including the following:

   1. Adequate bone marrow reserve:

      • absolute neutrophils (segmented and bands) count (ANC) ≥1.5x109/L;
      • platelets ≥100x109/L;
      • haemoglobin ≥9 g/dL.

   2. Hepatic:

      • bilirubin ≤ 1xULN;
      • alkaline phosphatase (AP);
      • aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5xULN.

   3. Renal:

      • serum creatinine ≤ 1.3 mg/dL
      • glomerular filtration rate (GFR) ≥ 70 mL/min for cisplatinum based CTx;
      • If contraindications including GFR below 70mL/minagainst cisplatin exist, carboplatin may also be used;
      • glomerular filtration rate ≥ 30 mL/min (calculated) if carboplatin is to be used
7. Adequate lung function tests as assessed by body plethysmography, diffusion test and if necessary spiro-ergometry.

8. Cooperation and willingness to complete all aspects of the study;

   • Written informed consent to participate in the study.

Exclusion Criteria:

1. EGFR wild type configuration;
2. EGFR resistance mutations (i.e. T790M);
3. Significant cardiovascular disease, such as uncontrolled hypertension, myocardial infarction within the last 6 months, unstable angina pectoris, CHF ≥ NYHA 2, serious arrhythmia, significant peripheral vascular disease;
4. Pre-existing neuropathic ≥ grade 2;
5. Patients with confirmed HIV infection. HIV testing is not mandatory.
6. Prior history of malignancy except for basal cell carcinoma or carcinoma in situ of the cervix, and with the exception of other malignancies after curative treatment with an interval of at least 3 years.
7. Lactating or pregnant woman, woman of child-bearing potential who do not agree to the usage of highly effective contraception methods (allowed methods of contraception, meaning methods with a rate of failure of less than 1% per year are implants, injectable contraceptives, combined oral contraceptives, intrauterine devices (only hormonal devices), sexual abstinence or vasectomy of the partner). Woman of childbearing potential must have a negative pregnancy test (serum β-HCG) at visit 1.
8. Any other chemotherapy at start;
9. Treatment with other experimental drugs during the course of the study or within the last 30 days or 7 half-lifes, whatever is of longer duration, prior study start;
10. Any psychiatric illness that would affect the patient's ability to understand the demands of the clinical trial;
11. Parallel participation in another clinical trial or participation in another clinical trial within the last 30 days or 7 half-lifes, whatever is of longer duration, prior study start;
12. Patient has already been included in this trial;
13. Patients who do not understand the nature, the scope and the consequences of the clinical trial;
14. Affected persons who might be dependent on the sponsor or the investigator.