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

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03755102
• Other study ID #: 18-341
• Status: Completed
• Phase: Early Phase 1
• Start date: November 21, 2018
• Est. completion date: July 7, 2023

Study information

• Verified date: November 2022
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: July 7, 2023
• Est. primary completion date: July 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• EGFR Gene Mutation
• Lung Cancer
• Lung Cancer Metastatic
• Lung Neoplasms

Intervention

Drug:
• Dacomitinib
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
• Osimertinib
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

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Rockville Centre	Rockville Centre	New York
United States	Memorial Sloan Kettering Nassau	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate	Overall response rate (partial and complete responses) of dacomitinib in participants with EGFR-mutant lung cancers and disease progression on osimertinib	1 year
Secondary	Progression-free survival		1 year
Secondary	Overall survival		1 year

External Links

•   Memorial Sloan Kettering Cancer Center