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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03567642
Recruitment Status : Recruiting
First Posted : June 26, 2018
Last Update Posted : July 2, 2020
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE June 13, 2018
First Posted Date  ICMJE June 26, 2018
Last Update Posted Date July 2, 2020
Actual Study Start Date  ICMJE June 12, 2018
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 13, 2018)
The MTD (maximum tolerated dose) [ Time Frame: 2 years ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Combination of Osimertinib, Platinum and Etoposide for Patients With Metastatic EGFR Mutant Lung Cancers
Official Title  ICMJE Phase 1 Study of Combination Osimertinib, Platinum, Etoposide for Patients With Metastatic EGFR Mutant Lung Cancers With Concurrent RB1 and TP53 Alterations
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lung Cancer
Intervention  ICMJE
  • Drug: Osimertinib
    Osimertinib 80mg daily
  • Drug: Platinum
    Cisplatin 60mg/m2 or Cisplatin 45mg/m2 Carboplatin AUC 5 or Carboplatin AUC 4
  • Drug: Etoposide
    Etoposide 100mg/m2 or Etoposide 80mg/m2
Study Arms  ICMJE Experimental: Osimertinib, Platinum (cisplatin or carboplatin) and Etoposide
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.)
Interventions:
  • Drug: Osimertinib
  • Drug: Platinum
  • Drug: Etoposide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 13, 2018)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • QTc>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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Helena Yu, MD 646-888-4274 yuh@mskcc.org
Contact: Mark Kris, MD 646-888-4205
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03567642
Other Study ID Numbers  ICMJE 18-211
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Helena Yu, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP