Metastatic Non-small Cell Lung Cancer
Conditions
Keywords
Dacomitinib, Osimertinib, EGFR Mutant Lung Cancers, 18-411
Brief summary
The purpose of this study is to test the safety of dacomitinib and osimertinib, at increasing doses, to find out what effects, if any, this combination of drugs has on people with metastatic EGFR mutant lung cancer that has not been treated with an EGFR TKI.
Interventions
DRUGDacomitinib
Dose level 1 Dacomitinib, Dose level 2 Dacomitinib, Dose level 3 Dacomitinib. Three patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (28 days for cycle 1) before dose escalation decision is made.
DRUGOsimertinib
Dose level 1, 2 and 3 Osimertinib 40mg daily. Three patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (28 days for cycle 1) before dose escalation decision is made.
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent * Advanced biopsy-proven metastatic non-small cell lung cancer * Somatic activating mutation in EGFR in a tumor biopsy * No prior EGFR inhibitor treatment (gefitinib, afatinib, erlotinib, dacomitinib, osimertinib) however, prior treatment with other chemotherapies are allowed * Archival tissue available from a pre-treatment tumor biopsy or willing to undergo a tumor biopsy prior to study initiation. * Measurable (RECIST 1.1) indicator lesion not previously irradiated * Karnofsky performance status (KPS) ≥ 70% * Age \>18 years old * Ability to swallow oral medication * Agree to use effective methods of contraception from the time of screening until 3 months after treatment discontinuation (for males and females of child-bearing potential) * Adequate organ function * AST, ALT ≤ 3 x ULN * Total bilirubin ≤1.5x ULN * Creatinine ≤ 1.5x ULN OR calculated creatinine clearance ≥ 60ml/min * Absolute neutrophil count (ANC) ≥ 1000 cells/mm\^3 * Hemoglobin≥9.0 g/dL * Platelets ≥100,000/mm\^3
Exclusion criteria
* Pregnant or lactating women * Any radiotherapy within 1 week of starting treatment on protocol. * Any major surgery within 1 weeks of starting treatment on protocol. * Any evidence of active clinically significant interstitial lung disease * A mean QTc \>470ms (Fridericias correction), clinically important arrhythmia, conduction or morphology of resting ECG (eg complete LBBB, 1st -3rd degree heart block, any factors that increase the risk of QTc prolongation or risk of arrhythmia) * Cardiovascular disease or cerebrovascular disease, CVA or MI \< 6 months prior to study enrollment, unstable angina, NYHA \>Grade II CHF, or serious cardiac arrhythmia uncontrolled by medication or with the potential to interfere with protocol treatment * History of pneumonitis or interstitial lung disease (ILD), drug induced ILD, radiation pneumonitits that required steroid treatment, and any evidence of clinically active ILD * Serious chronic GI conditions associated with diarrhea * Symptomatic, unstable brain metastases requiring escalating doses of steroids * Continue to have unresolved \> CTCAE grade 1 toxicity from any previous treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| maximum tolerated dose | 1 year | The MTD will be defined as the highest dose at which not more than 1/6 of the patients experience dose limiting toxicity (DLT). DLT is defined as any of the toxicity events described below that occurs within cycle 1 of treatment with the combination of dacomitinib and osimertinib. |
| Best overall response rate | 1 year | Tumor response will be assessed using RECIST 1.1.The NCI Common Terminology Criteria for Adverse Events Version 5 (NCI-CTCAE) will be used to grade toxicities during the trial. Dose-limiting toxicities (DLTs) are defined as any of the following events occurring during the first cycle of treatment |
Countries
United States
Outcome results
None listed