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A Pilot Study of Dacomitinib With or Without Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers With Disease Progression on Osimertinib.

Primary Purpose

EGFR Gene Mutation, Lung Cancer, Lung Cancer Metastatic

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

About this trial

This is an interventional treatment trial for EGFR Gene Mutation focused on measuring EGFR C797S, EGFR mutant lung cancer, dacomitinib, osimertinib, 18-341, Memorial Sloan Kettering Cancer Center

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
  • Somatic activating mutation in EGFR in a tumor biopsy or plasma cfDNA liquid biopsy
  • Prior treatment with osimertinib with response followed by disease progression
  • No prior first or second generation EGFR inhibitor treatment (gefitinib, afatinib, erlotinib)
  • Archival tissue available from a tumor biopsy done after disease progression on osimertinib or willing to undergo a tumor biopsy or liquid biopsy after disease progression on osimertinib prior to study initiation
  • 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/mm3
    • Hemoglobin>/=8.0 g/dL
    • Platelets >/=75,000/mm3

Exclusion Criteria:

  • Pregnant or lactating women
  • 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 Treatment
  • Patients with a known mechanism of resistance to osimertinib that will clearly not respond to dacomitinib therapy (i.e. known MET amplification, ALK fusion, RET fusion).
  • Symptomatic brain metastases or leptomeningeal disease requiring escalating doses of steroids

Sites / Locations

  • Memorial Sloan Kettering Basking Ridge
  • Memorial Sloan Kettering Monmouth
  • Memorial Sloan Kettering Bergen
  • Memorial Sloan Kettering Commack
  • Memorial Sloan Kettering Westchester
  • Memorial Sloan Kettering Cancer Center
  • Memorial Sloan Kettering Rockville Centre
  • Memorial Sloan Kettering Nassau

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort 1: Participants treated with dacomitinib alone

Cohort 2: Participants treated with dacomitinib in combination with osimertinib

Arm Description

Participants in this cohort have a somatic activating mutation in EGFR in a tumor biopsy or plasma cfDNA liquid biopsy.

Participants in this cohort have a secondary acquired EGFR mutation in addition to the sensitizing mutation

Outcomes

Primary Outcome Measures

Overall Response Rate
Overall response rate (partial and complete responses) of dacomitinib in participants with EGFR-mutant lung cancers and disease progression on osimertinib

Secondary Outcome Measures

Progression-free survival
Overall survival

Full Information

First Posted
November 26, 2018
Last Updated
July 10, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT03755102
Brief Title
A Pilot Study of Dacomitinib With or Without Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers With Disease Progression on Osimertinib.
Official Title
A Pilot Study of Dacomitinib With or Without Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers With Disease Progressionon Osimertinib.
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
November 21, 2018 (Actual)
Primary Completion Date
July 7, 2023 (Actual)
Study Completion Date
July 7, 2023 (Actual)

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

5. Study Description

Brief Summary
The purpose of this study is to assess whether dacomitinib after osimertinib is effective in participants with metastatic EGR-mutant lung cancers.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
EGFR Gene Mutation, Lung Cancer, Lung Cancer Metastatic
Keywords
EGFR C797S, EGFR mutant lung cancer, dacomitinib, osimertinib, 18-341, Memorial Sloan Kettering Cancer Center

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: Participants treated with dacomitinib alone
Arm Type
Experimental
Arm Description
Participants in this cohort have a somatic activating mutation in EGFR in a tumor biopsy or plasma cfDNA liquid biopsy.
Arm Title
Cohort 2: Participants treated with dacomitinib in combination with osimertinib
Arm Type
Experimental
Arm Description
Participants in this cohort have a secondary acquired EGFR mutation in addition to the sensitizing mutation
Intervention Type
Drug
Intervention Name(s)
Dacomitinib
Intervention Description
Cohort 1 Dacomitinib Dosing: Dose level 1: Dacomitinib 45mg daily Dose level -1: Dacomitinib 30mg daily Dose level -2: Dacomitinib 15mg daily Cohort 2 Dacomitinib Dosing: Dose level 1: Dacomitinib 30 mg daily Dose level -1: Dacomitinib 15 mg daily
Intervention Type
Drug
Intervention Name(s)
Osimertinib
Intervention Description
In cohort 2, participants will begin on dacomitinib orally daily in combination with Osimertinib Dose level Osimertinib Dosing: Dose level 1: Osimertinib 80 mg daily Dose level -1: Osimertinib 40 mg daily
Primary Outcome Measure Information:
Title
Overall Response Rate
Description
Overall response rate (partial and complete responses) of dacomitinib in participants with EGFR-mutant lung cancers and disease progression on osimertinib
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Progression-free survival
Time Frame
1 year
Title
Overall survival
Time Frame
1 year

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 Somatic activating mutation in EGFR in a tumor biopsy or plasma cfDNA liquid biopsy Prior treatment with osimertinib with response followed by disease progression No prior first or second generation EGFR inhibitor treatment (gefitinib, afatinib, erlotinib) Archival tissue available from a tumor biopsy done after disease progression on osimertinib or willing to undergo a tumor biopsy or liquid biopsy after disease progression on osimertinib prior to study initiation 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/mm3 Hemoglobin>/=8.0 g/dL Platelets >/=75,000/mm3 Exclusion Criteria: Pregnant or lactating women 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 Treatment Patients with a known mechanism of resistance to osimertinib that will clearly not respond to dacomitinib therapy (i.e. known MET amplification, ALK fusion, RET fusion). Symptomatic brain metastases or leptomeningeal disease requiring escalating doses of steroids
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Helen Yu, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Basking Ridge
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Facility Name
Memorial Sloan Kettering Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Facility Name
Memorial Sloan Kettering Bergen
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Facility Name
Memorial Sloan Kettering Commack
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memorial Sloan Kettering Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Memorial Sloan Kettering Rockville Centre
City
Rockville Centre
State/Province
New York
ZIP/Postal Code
11570
Country
United States
Facility Name
Memorial Sloan Kettering Nassau
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Links:
URL
http://www.mskcc.org
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

A Pilot Study of Dacomitinib With or Without Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers With Disease Progression on Osimertinib.

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