Clinical trial NCT03567642: A Study of the Combination of Osimertinib, Platinum and Etoposide for Patients With Metastatic EGFR Mutant Lung Cancers
Official title: Phase 1 Study of Combination Osimertinib, Platinum, Etoposide for Patients With Metastatic EGFR Mutant Lung Cancers With Concurrent RB1 and TP53 Alterations
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Lung Cancer
Keywords: Osimertinib
Platinum
Etoposide
EGFR Mutant
18-211
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2018-06-26
Enrollment: 11
Sex: ALL
Minimum age (years): 18
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 combining Osimertinib with either Cisplatin or Carboplatin (at different dose levels) and Etoposide, to find out what effects, if any, this combination of drugs has on people with EGFR mutant lung cancer.


Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Advanced biopsy-proven metastatic non-small cell lung cancer
* Either have not started an EGFR TKI or may have started osimertinib within the last 9 weeks
* Somatic activating mutation in EGFR in pre-treatment tumor biopsy or cfDNA
* Evidence of a concurrent P53 alteration by IHC or NGS on pre-treatment tumor biopsy or cfDNA
* Evidence of a concurrent RB1 alteration by IHC or NGS on pre-treatment tumor biopsy or cfDNA
* Must have a site of disease amenable to repeat biopsy and be willing to undergo a biopsy during treatment
* 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/mm\^3
  * Hemoglobin≥8.0 g/dL
  * Platelets ≥100,000/mm\^3

Exclusion Criteria:

* Pregnant or lactating women
* Started an EGFR TKI other than osimertinib or started osimertinib more than 9 weeks ago
* 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
* Have pure small cell histology
* Corrected QT interval using Fridericia's formula (QTcF)\>475msec or any clinically significant (as deemed by the investigator) abnormalities in rhythm or conduction or morphology of the resting EKG.
* Patients are to be excluded from cisplatin treatment arm if they meet any of the following criteria:
* Creatinine clearance \< 60 ml/min
* Hearing impairment requiring assistive device
* Neuropathy
* The treating provider does not feel as though the patient should receive cisplatin

Primary outcomes:
measure: The MTD (maximum tolerated dose)
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Cancer Center
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: