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Study of Dacomitinib and Osimertinib for Patients With Advanced EGFR Mutant Lung Cancer

Primary Purpose

Metastatic Non-small Cell Lung Cancer

Status
Active
Phase
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 Metastatic Non-small Cell Lung Cancer focused on measuring Dacomitinib, Osimertinib, EGFR Mutant Lung Cancers, 18-411

Eligibility Criteria

19 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
  • No prior EGFR inhibitor treatment (gefitinib, afatinib, erlotinib, dacomitinib, osimertinib) however, prior treatment with other chemotherapies are allowed
  • Archival tissue available from a pre-treatment tumor biopsy or willing to undergo a tumor biopsy 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
  • Agree to use effective methods of contraception from the time of screening until 3 months after treatment discontinuation (for males and females of child-bearing potential)

  • 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≥9.0 g/dL
    • Platelets ≥100,000/mm^3

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
  • A mean QTc >470ms (Fridericia"s correction), clinically important arrhythmia, conduction or morphology of resting ECG (eg complete LBBB, 1st -3rd degree heart block, any factors that increase the risk of QTc prolongation or risk of arrhythmia)
  • Cardiovascular disease or cerebrovascular disease, CVA or MI < 6 months prior to study enrollment, unstable angina, NYHA >Grade II CHF, or serious cardiac arrhythmia uncontrolled by medication or with the potential to interfere with protocol treatment
  • History of pneumonitis or interstitial lung disease (ILD), drug induced ILD, radiation pneumonitits that required steroid treatment, and any evidence of clinically active ILD
  • Serious chronic GI conditions associated with diarrhea
  • Symptomatic, unstable brain metastases requiring escalating doses of steroids
  • Continue to have unresolved > CTCAE grade 1 toxicity from any previous treatment

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 Nassau

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dacomitinib and Osimertinib

Arm Description

Patients will begin on combination dacomitinib and osimertinib at the prescribed doses. A cycle will be 28 days in duration. The study will use a standard 3+3 dose escalation design. Per MD discretion, telemedicine visits may be utilized for cycles where imaging is not collected, and physical exam, vital sign and labs collection will only be required concurrent with imaging visits.

Outcomes

Primary Outcome Measures

maximum tolerated dose
The MTD will be defined as the highest dose at which not more than 1/6 of the patients experience dose limiting toxicity (DLT). DLT is defined as any of the toxicity events described below that occurs within cycle 1 of treatment with the combination of dacomitinib and osimertinib.
Best overall response rate
Tumor response will be assessed using RECIST 1.1.The NCI Common Terminology Criteria for Adverse Events Version 5 (NCI-CTCAE) will be used to grade toxicities during the trial. Dose-limiting toxicities (DLT"s) are defined as any of the following events occurring during the first cycle of treatment

Secondary Outcome Measures

Full Information

First Posted
January 17, 2019
Last Updated
June 30, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT03810807
Brief Title
Study of Dacomitinib and Osimertinib for Patients With Advanced EGFR Mutant Lung Cancer
Official Title
Phase 1 Study of Combination Dacomitinib and Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 17, 2019 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
January 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

5. Study Description

Brief Summary
The purpose of this study is to test the safety of dacomitinib and osimertinib, at increasing doses, to find out what effects, if any, this combination of drugs has on people with metastatic EGFR mutant lung cancer that has not been treated with an EGFR TKI.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Non-small Cell Lung Cancer
Keywords
Dacomitinib, Osimertinib, EGFR Mutant Lung Cancers, 18-411

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Dacomitinib and Osimertinib
Arm Type
Experimental
Arm Description
Patients will begin on combination dacomitinib and osimertinib at the prescribed doses. A cycle will be 28 days in duration. The study will use a standard 3+3 dose escalation design. Per MD discretion, telemedicine visits may be utilized for cycles where imaging is not collected, and physical exam, vital sign and labs collection will only be required concurrent with imaging visits.
Intervention Type
Drug
Intervention Name(s)
Dacomitinib
Intervention Description
Dose level 1 Dacomitinib, Dose level 2 Dacomitinib, Dose level 3 Dacomitinib. Three patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (28 days for cycle 1) before dose escalation decision is made.
Intervention Type
Drug
Intervention Name(s)
Osimertinib
Intervention Description
Dose level 1, 2 and 3 Osimertinib 40mg daily. Three patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (28 days for cycle 1) before dose escalation decision is made.
Primary Outcome Measure Information:
Title
maximum tolerated dose
Description
The MTD will be defined as the highest dose at which not more than 1/6 of the patients experience dose limiting toxicity (DLT). DLT is defined as any of the toxicity events described below that occurs within cycle 1 of treatment with the combination of dacomitinib and osimertinib.
Time Frame
1 year
Title
Best overall response rate
Description
Tumor response will be assessed using RECIST 1.1.The NCI Common Terminology Criteria for Adverse Events Version 5 (NCI-CTCAE) will be used to grade toxicities during the trial. Dose-limiting toxicities (DLT"s) are defined as any of the following events occurring during the first cycle of treatment
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 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 No prior EGFR inhibitor treatment (gefitinib, afatinib, erlotinib, dacomitinib, osimertinib) however, prior treatment with other chemotherapies are allowed Archival tissue available from a pre-treatment tumor biopsy or willing to undergo a tumor biopsy 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 Agree to use effective methods of contraception from the time of screening until 3 months after treatment discontinuation (for males and females of child-bearing potential) 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≥9.0 g/dL Platelets ≥100,000/mm^3 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 A mean QTc >470ms (Fridericia"s correction), clinically important arrhythmia, conduction or morphology of resting ECG (eg complete LBBB, 1st -3rd degree heart block, any factors that increase the risk of QTc prolongation or risk of arrhythmia) Cardiovascular disease or cerebrovascular disease, CVA or MI < 6 months prior to study enrollment, unstable angina, NYHA >Grade II CHF, or serious cardiac arrhythmia uncontrolled by medication or with the potential to interfere with protocol treatment History of pneumonitis or interstitial lung disease (ILD), drug induced ILD, radiation pneumonitits that required steroid treatment, and any evidence of clinically active ILD Serious chronic GI conditions associated with diarrhea Symptomatic, unstable brain metastases requiring escalating doses of steroids Continue to have unresolved > CTCAE grade 1 toxicity from any previous treatment
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 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 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.
Citations:
PubMed Identifier
34140482
Citation
Poels KE, Schoenfeld AJ, Makhnin A, Tobi Y, Wang Y, Frisco-Cabanos H, Chakrabarti S, Shi M, Napoli C, McDonald TO, Tan W, Hata A, Weinrich SL, Yu HA, Michor F. Identification of optimal dosing schedules of dacomitinib and osimertinib for a phase I/II trial in advanced EGFR-mutant non-small cell lung cancer. Nat Commun. 2021 Jun 17;12(1):3697. doi: 10.1038/s41467-021-23912-4. Erratum In: Nat Commun. 2022 Sep 23;13(1):5579.
Results Reference
derived
Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

Study of Dacomitinib and Osimertinib for Patients With Advanced EGFR Mutant Lung Cancer

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