Phase 2
Completed N=231
Study Of Dacomitinib (PF-00299804) In Advanced NSCLC Patients (Post Chemo Or Select First Line) To Evaluate Prophylactic Intervention On Derm And GI AEs And PRO
Source: ClinicalTrials.gov NCT01465802 ↗Enrolled (actual)
231
Serious AEs
35.9%
Results posted
Aug 2016
Primary outcomePrimary: Percentage of Participants With Select Dermatologic Adverse Events of Interest (SDAEI) (All Causality, All Grade) in the First 8 Weeks of Treatment by Treatment Arm for Cohort I — 79.3; 75.0 Percentage of Participants
Summary
To assess the impact of prophylactic treatment on the incidence of adverse events in advanced NSCLC patients (post chemotherapy) treated with dacomitinib daily as a single agent. To assess the impact of an interrupted dacomitinib dosing schedule in Cycle 1 on the incidence of adverse events in first-line advanced NSCLC patients with an EGFR mutation (HER-1 mutation, HER-2 mutation or HER-2 amplification).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Select Dermatologic Adverse Events of Interest (SDAEI) (All Causality, All Grade) in the First 8 Weeks of Treatment by Treatment Arm for Cohort I |
79.3; 75.0 | — |
| PRIMARY Percentage of Participants With SDAEI (All Causality, Grade Greater Than or Equal to [≥] 2) in the First 8 Weeks of Treatment by Treatment Arm for Cohort I |
46.6; 23.2 | — |
| PRIMARY Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) by Treatment Arm for Cohort I |
2.3; -1.1; 9.4; 21.4; 5.0; 30.6 | — |
| PRIMARY Percentage of Participants With Diarrhea AEs (All Causality, All Grade and Grade ≥2) in the First 8 Weeks of Treatment for Cohort II |
83.1; 39.0 | — |
| PRIMARY Mean Change From Baseline (Cycle 1 Day 1) Modified Oral Mucositis Daily Questionnaire (OMDQ) Scores (Mouth and Throat Soreness Categories and Scale, and Diarrhea Categories and Scale) for Cohort II |
0.8; 2.5; 2.6; 2.5; 1.9; 1.7 | — |
| PRIMARY Percentage of Participants With SDAEI (All Causality, All Grade) in the First 8 Weeks of Treatment for Cohort II |
79.7 | — |
| PRIMARY Percentage of Participants With SDAEI (All Causality, Grade ≥2) in the First 8 Weeks of Treatment for Cohort II |
35.6 | — |
| PRIMARY Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II |
0.1; 11.4; 11.4; 11.4; 13.5; 14.7 | — |
| PRIMARY Mean Area Under the Plasma Concentration Time Curve From 0 to 24 Hours (AUC0-24) and From 0 to 120 Hours (AUC0-120) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III |
1712.88; 5743.60; 184.62; 742.32 | — |
| PRIMARY Mean Maximum Observed Plasma Concentrations (Cmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III |
79.68; 8.5176 | — |
| PRIMARY Median Time of Occurrence of Cmax (Tmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III |
5.850; 5.980 | — |
| SECONDARY Percentage of Participants Receiving Any Concomitant Drug or Non-Drug Treatment for SDAEI, Diarrhea and Mucositis for Cohort I by Treatment Arm, Cohort II, and Cohort III |
69.7; 60.6; 85.7; 82.1; 88.0; 16.7 | — |
| SECONDARY Mean AUC From 0 to the End of the Dosing Interval (AUC0-tau) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I |
1801.96; 1869.23; 1412.42; 164.520; 112.306; 366.933 | — |
| SECONDARY Mean Cmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I |
88.15; 89.79; 98.08; 7.7426; 5.2901; 8.8545 | — |
| SECONDARY Median Tmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I |
4.000; 6.000; 6.580; 4.050; 4.020; 6.580 | — |
| SECONDARY Mean Apparent Clearance (CL/F) for Dacomitinib on Cycle 2 Day 1 for Cohort I |
29.94; 24.07; 34.24 | — |
| SECONDARY Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III |
65.477; 65.063; 56.212; 66.338; 55.780; 61.592 | — |
| SECONDARY Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III |
6.988; 4.653; 10.220; 7.814; 9.967; 5.555 | — |
Eligibility Criteria
Inclusion Criteria
- Advanced Non-Small Cell Lung Cancer (NSCLC).
- For Cohort I and Cohort II, advanced NSCLC patients must have received at least one prior regimen of systemic therapy which includes at least one standard chemotherapy for advanced NSCLC and who have failed (ie, progressed or intolerant due to toxicity which precludes further treatment) standard therapy for advanced or metastatic disease. To be considered intolerant to treatment, a patient must have received at least two cycles to be considered previously treated.
- For Cohort III, advanced NSCLC patients must not have received prior systemic treatment for their advanced disease and require a known EGFR (HER-1) mutation, HER-2 mutation or HER-2 amplification. Cohort III patients could have received prior adjuvant chemotherapy for Stage I-III disease or combined modality chemotherapy-radiation for Stage IIIA disease is allowed if treatment completed>12 months prior to enrollment.
- All cohorts, patients must have evidence of disease; however, measurable disease is not required to enroll.
- Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
- Estimated creatinine clearance ≥15 mL/min.
Exclusion Criteria
- Prior treatment with an EGFR-targeted or HER-targeted agent (all cohorts).
- Chemotherapy, radiotherapy, biological or investigational agents within 2 weeks of baseline disease assessments (all cohorts).
- Patients with known diffuse interstitial lung disease (all cohorts).
- Investigational therapy as only treatment for advanced NSCLC without administration of an approved chemotherapy for advanced NSCLC (for Cohort I and Cohort II)
Data sourced from ClinicalTrials.gov (NCT01465802). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.