A Study of the Combination of Osimertinib, Platinum and Etoposide for Patients With Metastatic EGFR Mutant Lung Cancers

Lung Cancer Clinical Trial

Official title:

Phase 1 Study of Combination Osimertinib, Platinum, Etoposide for Patients With Metastatic EGFR Mutant Lung Cancers With Concurrent RB1 and TP53 Alterations

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03567642
• Other study ID #: 18-211
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: June 12, 2018
• Est. completion date: June 2024

Study information

• Verified date: February 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 11
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• Osimertinib
Osimertinib 80mg daily
• Platinum
Cisplatin 60mg/m2 or Cisplatin 45mg/m2 Carboplatin AUC 5 or Carboplatin AUC 4
• Etoposide
Etoposide 100mg/m2 or Etoposide 80mg/m2

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Nassau	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The MTD (maximum tolerated dose)	Determine the safety and toxicity profile of combination osimertinib, platinum (cisplatin or carboplatin), etoposide for patients with metastatic EGFR mutant lung cancers with concurrent RB1 and TP53 alterations.	2 years

External Links

•   Memorial Sloan Kettering Cancer Center