Clinical trial NCT03810807: Study of Dacomitinib and Osimertinib for Patients With Advanced EGFR Mutant Lung Cancer
Official title: Phase 1 Study of Combination Dacomitinib and Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Metastatic Non-small Cell Lung Cancer
Keywords: Dacomitinib
Osimertinib
EGFR Mutant Lung Cancers
18-411
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2019-01-22
Enrollment: 22
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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
* 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 (Fridericia"s 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

Primary outcomes:
measure: maximum tolerated dose
timeFrame: 1 year
measure: Best overall response rate
timeFrame: 1 year
Secondary outcomes:
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: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Helena Yu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Poels KE, Schoenfeld AJ, Makhnin A, Tobi Y, Wang Y, Frisco-Cabanos H, Chakrabarti S, Shi M, Napoli C, McDonald TO, Tan W, Hata A, Weinrich SL, Yu HA, Michor F. Identification of optimal dosing schedules of dacomitinib and osimertinib for a phase I/II trial in advanced EGFR-mutant non-small cell lung cancer. Nat Commun. 2021 Jun 17;12(1):3697. doi: 10.1038/s41467-021-23912-4.