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

Primary Purpose

Lung Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Osimertinib
Platinum
Etoposide
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring Osimertinib, Platinum, Etoposide, EGFR Mutant, 18-211

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Memorial Sloan Kettering Cancer CenterRecruiting
  • Memorial Sloan Kettering MonmouthRecruiting
  • Memorial Sloan Kettering BergenRecruiting
  • Memorial Sloan Kettering CommackRecruiting
  • Memorial Sloan Kettering WestchesterRecruiting
  • Memorial Sloan Kettering Cancer CenterRecruiting
  • Memorial Sloan Kettering NassauRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Osimertinib, Platinum (cisplatin or carboplatin) and Etoposide

Arm Description

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.)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
June 13, 2018
Last Updated
June 29, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT03567642
Brief Title
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

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 12, 2018 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center

4. Oversight

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

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer
Keywords
Osimertinib, Platinum, Etoposide, EGFR Mutant, 18-211

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Osimertinib, Platinum (cisplatin or carboplatin) and Etoposide
Arm Type
Experimental
Arm Description
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.)
Intervention Type
Drug
Intervention Name(s)
Osimertinib
Intervention Description
Osimertinib 80mg daily
Intervention Type
Drug
Intervention Name(s)
Platinum
Intervention Description
Cisplatin 60mg/m2 or Cisplatin 45mg/m2 Carboplatin AUC 5 or Carboplatin AUC 4
Intervention Type
Drug
Intervention Name(s)
Etoposide
Intervention Description
Etoposide 100mg/m2 or Etoposide 80mg/m2
Primary Outcome Measure Information:
Title
The MTD (maximum tolerated dose)
Description
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.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Helena Yu, MD
Phone
646-888-4274
Email
yuh@mskcc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Mark Kris, MD
Phone
646-888-4205
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Helena Yu, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Helena Yu, MD
Phone
646-888-4274
Facility Name
Memorial Sloan Kettering Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Helena Yu, MD
Phone
646-888-4274
Facility Name
Memorial Sloan Kettering Bergen
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Helena Yu, MD
Phone
646-888-4274
Facility Name
Memorial Sloan Kettering Commack
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Helena Yu, MD
Phone
646-888-4274
Facility Name
Memorial Sloan Kettering Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Helena Yu, MD
Phone
646-888-4274
First Name & Middle Initial & Last Name & Degree
Helena Yu, MD
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Helena Yu, MD
Phone
646-888-4274
First Name & Middle Initial & Last Name & Degree
Mark Kris, MD
Phone
646-888-4205
First Name & Middle Initial & Last Name & Degree
Helena Yu, MD
Facility Name
Memorial Sloan Kettering Nassau
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Helena Yu, MD
Phone
646-888-4274

12. IPD Sharing Statement

Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

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