non-small cell lung cancer
Conditions
Interventions
In phase I, all patients will be treated with dacomitinib + PD-0325901. Start
doses are dacomitinib 30 mg once daily and PD-0325901 2 mg twice daily during
the first 21 days of every 28 day cycle. G
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Histological or cytological proof of metastatic NSCLC 2. Written documentation of a known pathogenic KRAS (exon 2, 3 or 4) mutation and PIK3CA wildtype (exon 9 and 20). 3. Age >
Exclusion criteria
Exclusion criteria: 1. Any treatment with investigational drugs within 30 days prior to receiving the first dose of investigational treatment. 2. History of additional prior malignancies. 3. Symptomatic or untreated leptomeningeal disease. 4. Symptomatic brain metastasis. 5. Patients previously treated with any targeted drug combination known to interfere with EGFR, HER-2, HER-3, HER-4 or MAPK- and PI3K-pathway components, including inhibitors of PTEN, PI3K, AKT, mTOR, BRAF, MEK and ERK. 6. History of interstitial lung disease or pneumonitis 7. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral dacomitinib/PD-0325901 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection). 8. Woman who are pregnant or breast feeding. 9. Unreliable contraceptive methods. 10. Radio-, immuno- or chemotherapy within the last 4 weeks prior to receiving the first dose of investigational treatment. Palliative radiation (1x 8Gy) is allowed. 11. Patients who have undergone any major surgery within the last 2 weeks prior to starting study drug or who would not have fully recovered from previous surgery. 12. Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients. 13. Patients with a known history of hepatitis B or C.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose-limiting toxicities (DLTs) Progression free survival (PFS) per RECIST version 1.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Incidence and severity of adverse events Overall response rate, duration of response, time to response and overall survival (phase II only) Plasma concentrations of dacomitinib, PD-0325901 and relevant metabolites Baseline molecular status of potential predictive markers of tumor response (BRAF, HRAS, KRAS, NRAS, PTEN, PIK3CA, MAPK1, MAPK2, ARAF, c-MET, EGFR etc.) Gene alteration (baseline, relapse) in tumor tissue | — |
Countries
Netherlands
Outcome results
None listed