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

NCT ID: NCT03810807

Last Updated: 2025-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-17

Study Completion Date

2025-12-15

Brief Summary

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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.

Detailed Description

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Conditions

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Metastatic Non-small Cell Lung Cancer

Keywords

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Dacomitinib Osimertinib EGFR Mutant Lung Cancers 18-411

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dacomitinib and Osimertinib

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.

Group Type EXPERIMENTAL

Dacomitinib

Intervention Type DRUG

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.

Osimertinib

Intervention Type DRUG

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.

Interventions

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Dacomitinib

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

Osimertinib

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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Helena Yu, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Site Status

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States

Site Status

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

Site Status

Memorial Sloan Kettering Commack

Commack, New York, United States

Site Status

Memorial Sloan Kettering Westchester

Harrison, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 34140482 (View on PubMed)

Related Links

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http://www.mskcc.org/mskcc/html/44.cfm

Memorial Sloan Kettering Cancer Center

Other Identifiers

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18-411

Identifier Type: -

Identifier Source: org_study_id