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.
Active, not recruiting
Phase 1
| Drug | Synonyms | Arms |
|---|---|---|
| Dacomitinib | Dacomitinib and Osimertinib | |
| Osimertinib | Dacomitinib and Osimertinib |
| Name | Type | Description | Interventions |
|---|---|---|---|
| Dacomitinib and Osimertinib | Experimental | 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. |
|
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 19 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | maximum tolerated dose |
| Time Frame: | 1 year |
| Safety Issue: | |
| 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. |
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Memorial Sloan Kettering Cancer Center |
February 23, 2021
