Combining Afatinib and Concurrent Chemotherapy, Followed by Osimertinib and Concurrent Chemotherapy, in Untreated EGFR Positive NSCLC Tumors

Recruiting

Conditions: on small cell lung cancer

Registration Number: NL-OMON28617

Lead Sponsor: Amsterdam UMC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 21

Inclusion Criteria

1. Histologically confirmed NSCLC, positive for EGFR exon 19 deletion or EGFR exon 21 L858R
2. WHO PS 0-2
3. Be willing and able to provide written informed consent for the trial.
4. Be above 18 years of age on day of signing informed consent.
5. Patients must have radiological measurable disease
6. Demonstrate adequate organ function, as deemed acceptable by the treating physician in the context of metastatic NSCLC:
a. Leukocytes = 3,000/mm3
b. Absolute neutrophil count (ANC) = 1500/mm3
c. Platelet count = 100,000/mm3
d. Hemoglobin = 6 mmol/L
e. Creatinine = 1.5 x ULN or creatinine clearance (CrCl) =40 mL/min (if using the Cockcroft-Gault formula below):
i. Female CrCl = [(140 - age) x weight x 0.85]/(0.85 x creat in mmol/L)
ii. Male CrCl = [(140 - age) x weight x 1.00]/(0.81 x creat in mmol/L)
f. Total Bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome)
g. AST and ALT = 3 times the upper limit of normal

Exclusion Criteria

1. Inability to provide informed consent
2. Inability to take study medications
3. Patients with CNS metastases
4. Prior EGFR TKI or platinum-doublet therapy for advanced stage NSCLC. Prior (neo)adjuvant treatments are allowed when the last administration is one year or more.
5. Evidence of interstitial lung disease or active, non-infectious pneumonitis.
6. Active infection requiring systemic therapy.
7. Active Hepatitis B or C.
8. Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
9. Patient is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the screening visit.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Disease control rate (DCR) at 18 months, defined as the rate of patients that are still on treatment using either afatinib or osimertinib without radiological disease progression according to RECIST (v1.1). If patients develop oligo-progressive disease that is amenable to local treatments such as stereotactic radiotherapy and if the patient has clinical benefit of the ongoing TKI treatment, the treating physician may (in the best interest of the patient) treat the oligo-progressive site(s) locally and continue the TKI (in part-1 and part-2) beyond progression, as per current standard of care guidelines. The efficacy of this sequential approach will be compared to the front-line osimertinib outcome data, as reported by the FLAURA trial.

Secondary Outcome Measures

Name	Time	Method
1. Progression Free Survival (PFS) as determined using Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and defined as time from initiation of afatinib to the development of new lesions, progression of existing lesions, or death, whichever comes first<br>2. Overall Survival (OS). Time frame: initiation of afatinib until death.<br>3. Objective response rate at 6 and 12 weeks according to RECIST v1.1 after start of afatinib<br>4. Objective response rate at 6 and 12 weeks according to RECIST v1.1 after start of osimertinib<br>5. Safety of afatinib and osimertinib intercalated with 2 cycles of carboplatin-pemetrexed.<br>Exploratory endpoints<br>1. The baseline tumor biopsy (and all archival biopsies) and additional blood samples (before start of afatinib, at defined timepoints during treatment and upon progression) will be used for assessing the time to disappearance and time to re-appearance of the EGFR mutation in ctDNA both after start of afatinib and osimertinib.