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

NCT03567642 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 18-211
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 7

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.

Conditions

Lung Cancer

Keywords

Osimertinib; Platinum; Etoposide; EGFR Mutant; 18-211

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Osimertinib, Platinum (cisplatin or carboplatin) and Etoposide

EXPERIMENTAL

Initially, 6 patients will be enrolled and will begin treatment with osimertinib 80mg orally daily (3 who will be receiving cisplatin and 3 who will be receiving carboplatin). Cisplatin or carboplatin treatment will be decided by the treating physician prior to study registration. After 9 weeks (+/- 1 week)( 3 cycles) on osimertinib alone, carboplatin or cisplatin and etoposide will be added. Carboplatin is doses at an AUC of 5 or cisplatin at 60mg/m2 will be given on C4D1. Etoposide is dosed at 100mg/m2 given on Days 1-3 of C4. Only patients on osimertinib 80mg orally daily at the start of cycle 4 will be included in the 3+3 dose de-escalation portion of the study. Chemotherapy and osimertinib will be administered concurrently during cycles 4-7, and from cycle 8 onward, osimertinib monotherapy will be continued. Patients will present every 2 cycles post-chemo (Cycles 8, 10, 12, etc.)

Drug: Osimertinib; Drug: Platinum; Drug: Etoposide

Interventions

Osimertinib DRUG

Osimertinib 80mg daily

Osimertinib, Platinum (cisplatin or carboplatin) and Etoposide

Platinum DRUG

Cisplatin 60mg/m2 or Cisplatin 45mg/m2 Carboplatin AUC 5 or Carboplatin AUC 4

Osimertinib, Platinum (cisplatin or carboplatin) and Etoposide

Etoposide DRUG

Etoposide 100mg/m2 or Etoposide 80mg/m2

Osimertinib, Platinum (cisplatin or carboplatin) and Etoposide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Cancer Center

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lung Neoplasms

Interventions

osimertinib; Platinum; Etoposide

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Helena Yu, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2018
• First Posted: June 26, 2018
• Study Start: June 12, 2018
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: July 3, 2025

Record last verified: 2025-07

Locations

US (7)