Clinical trial NCT03755102: A Pilot Study of Dacomitinib With or Without Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers With Disease Progression on Osimertinib.
Official title: A Pilot Study of Dacomitinib With or Without Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers With Disease Progressionon Osimertinib.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: EGFR Gene Mutation
Lung Cancer
Lung Cancer Metastatic
Keywords: EGFR C797S
EGFR mutant lung cancer
dacomitinib
osimertinib
18-341
Memorial Sloan Kettering Cancer Center
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2018-11-27
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess whether dacomitinib after osimertinib is effective in participants with metastatic EGR-mutant lung cancers.


Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Advanced biopsy-proven metastatic non-small cell lung cancer
* Somatic activating mutation in EGFR in a tumor biopsy or plasma cfDNA liquid biopsy
* Prior treatment with osimertinib with response followed by disease progression
* No prior first or second generation EGFR inhibitor treatment (gefitinib, afatinib, erlotinib)
* Archival tissue available from a tumor biopsy done after disease progression on osimertinib or willing to undergo a tumor biopsy or liquid biopsy after disease progression on osimertinib 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
* 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/mm3
  * Hemoglobin\>/=8.0 g/dL
  * Platelets \>/=75,000/mm3

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
* Continue to have unresolved \> grade 1 toxicity from any previous treatment Treatment
* Patients with a known mechanism of resistance to osimertinib that will clearly not respond to dacomitinib therapy (i.e. known MET amplification, ALK fusion, RET fusion).
* Symptomatic brain metastases or leptomeningeal disease requiring escalating doses of steroids

Primary outcomes:
measure: Overall Response Rate
timeFrame: 1 year
Secondary outcomes:
measure: Progression-free survival
timeFrame: 1 year
measure: Overall survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan Kettering Rockville Centre
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Helen Yu, MD
role: PRINCIPAL_INVESTIGATOR
References: