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

Metastatic Non-small Cell Lung Cancer Clinical Trial

Official title:

Phase 1 Study of Combination Dacomitinib and Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03810807
• Other study ID #: 18-411
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: January 17, 2019
• Est. completion date: January 2025

Study information

• Verified date: February 2024
• 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 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 22
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 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
• 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

Related Conditions & MeSH terms

• Lung Neoplasms
• Metastatic Non-small Cell Lung Cancer

Intervention

Drug:
• 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.
• 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.

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 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	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.	1 year
Primary	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	1 year

External Links

•   Memorial Sloan Kettering Cancer Center