lung cancer NSCLC
Conditions
Interventions
This study consists of 2 parts. Part 1 is defined as a first line treatment
with afatinib orally (30 mg once a day) for the first 6 weeks, followed by
concurrent use of afatinib (20mg once a day, pa
followed by afatinib
monotherapy (30mg once a day). Part 2 comprises a 2nd line treatment with
osimertinib (80 mg once daily) after failure of part 1, only in T790M positive
patients for the first
followed by osimertinib monotherapy (80mg once a day).
Sponsors
Vrije Universiteit Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Histologically confirmed NSCLC, positive for non-exon20insertion uncommon EGFR mutations that are eligible for afatinib therapy in first line - WHO PS 0-2 - Be willing and able to provide written informed consent for the trial. -Be above 18 years of age on day of signing informed consent. - Patients must have radiological measurable disease - Demonstrate adequate organ function, as deemed acceptable by the treating physician in the context of metastatic NSCLC: - Leukocytes >= 3,000/mm3 - Absolute neutrophil count (ANC) >= 1500/mm3 - Platelet count >= 100,000/mm3 - Hemoglobin >= 6 mmol/L - Creatinine =40 mL/min (if using the Cockcroft-Gault formula below): Female CrCl = [(140 - age) x weight x 0.85]/(0.85 x creat in mmol/L); Male CrCl = [(140 - age) x weight x 1.00]/(0.81 x creat in mmol/L) - Total Bilirubin
Exclusion criteria
Exclusion criteria: - Inability to provide informed consent - Inability to take study medications - Patients with symptomatic or unstable CNS metastases - 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. - Evidence of interstitial lung disease or active, non-infectious pneumonitis. - Active infection requiring systemic therapy. - Active Hepatitis B or C. - Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. - Patient is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the screening visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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). The efficacy of this sequential approach will be compared to the front-line osimertinib outcome data, as reported by the FLAURA trial. Safety will be monitored, especially in parts 1B and 2B. A safety run-in will be incorporated for part 1B, with a safety analysis after the 3rd and 6th patient. Tumor responses will be assessed by ORR. Clinical outcome parameters such as PFS, and OS, will be registered. ¬¬Post-study chemotherapy efficacy will be registered. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 2. Overall Survival (OS). Time frame: initiation of afatinib until death. 3. Objective response rate at 5 and 12 weeks according to RECIST v1.1 after start of afatinib 4. Objective response rate at 5 and 12 weeks according to RECIST v1.1 after start of osimertinib 5. Safety of afatinib and osimertinib intercalated with 2 cycles of carboplatin-pemetrexed. Safety, as defined as the percentage of patients with adverse events, will be assessed throughout the study. The causal association will be determined by the investigators. The severity of adverse events will be graded using the latest version National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). | — |
Countries
Netherlands
Outcome results
None listed