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

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ClinicalTrials.gov Identifier: NCT03567642
Recruitment Status : Recruiting
First Posted : June 25, 2018
Last Update Posted : May 16, 2019
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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.

Condition or disease Intervention/treatment Phase
Lung Cancer Drug: Osimertinib Drug: Platinum Drug: Etoposide Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Study of Combination Osimertinib, Platinum, Etoposide for Patients With Metastatic EGFR Mutant Lung Cancers With Concurrent RB1 and TP53 Alterations
Actual Study Start Date : June 12, 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020


Arm Intervention/treatment
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.)
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




Primary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03567642


Contacts
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Contact: Helena Yu, MD 646-888-4274 yuh@mskcc.org
Contact: Mark Kris, MD 646-888-4205

Locations
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United States, New Jersey
Memoral Sloan Kettering Cancer Center Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Helena Yu, MD    646-888-4274      
Memorial Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Helena Yu, MD    646-888-4274      
Memorial Sloan Kettering Bergen Recruiting
Montvale, New Jersey, United States, 07645
Contact: Helena Yu, MD    646-888-4274      
United States, New York
Memorial Sloan Kettering Commack Recruiting
Commack, New York, United States, 11725
Contact: Helena Yu, MD    646-888-4274      
Memorial Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Helena Yu, MD    646-888-4274      
Principal Investigator: Helena Yu, MD         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Helena Yu, MD    646-888-4274      
Contact: Mark Kris, MD    646-888-4205      
Principal Investigator: Helena Yu, MD         
Memorial Sloan Kettering Nassau Recruiting
Uniondale, New York, United States, 11553
Contact: Helena Yu, MD    646-888-4274      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Helena Yu, MD Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03567642     History of Changes
Other Study ID Numbers: 18-211
First Posted: June 25, 2018    Key Record Dates
Last Update Posted: May 16, 2019
Last Verified: May 2019

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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

Keywords provided by Memorial Sloan Kettering Cancer Center:
Osimertinib
Platinum
Etoposide
EGFR Mutant
18-211

Additional relevant MeSH terms:
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Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Cisplatin
Carboplatin
Etoposide
Etoposide phosphate
Osimertinib
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors