Phase 2
Completed N=85
A Study to Determine Safety, Tolerability and Pharmacokinetics of Oral Dabrafenib In Children and Adolescent Subjects
Source: ClinicalTrials.gov NCT01677741 ↗Enrolled (actual)
85
Serious AEs
45.9%
Results posted
Nov 2021
Primary outcomePrimary: Incidence of Treatment Emergent Adverse Events (AEs) in Part 1 (Dose Escalation) — 0; 0; 0; 1 Participants
Summary
This was a 2-part, Phase I/IIa, multi-center, open label, study in pediatric and adolescent patients with advanced BRAF V600 mutation-positive solid tumors. Part 1 was a dose escalation study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6 Design (RSD). Part 2 was an expansion study to further evaluate the safety, tolerability, and clinical activity of dabrafenib in 4 tumor-specific pediatric populations. Patients participated in only either part 1 or part 2 of the study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Incidence of Treatment Emergent Adverse Events (AEs) in Part 1 (Dose Escalation) |
0; 0; 0; 1; 0; 0 | — |
| PRIMARY Maximum Concentration (Cmax) of Dabrafenib |
1820; 1250; 1250; 1900; 1340; 1550 | — |
| PRIMARY Area Under the Concentration-time Curve Over the Dosing Interval (AUC(0-τ)) and AUC From Zero to Infinity (AUC(0-inf)) of Dabrafenib |
— | — |
| SECONDARY Pre-dose (Trough) Concentration (C Tau) of Dabrafenib and Its Metabolites |
11.9; 39.8; 50.7; 11.0; 42.7; 22.8 | — |
| SECONDARY The AUC(0-t) of Dabrafenib Metabolites |
— | — |
| SECONDARY The AUC(0-tau) of Dabrafenib and Its Metabolites |
— | — |
| SECONDARY Apparent Total Clearance of the Drug From Plasma After Oral Administration (CL/F) of Dabrafenib |
— | — |
| SECONDARY Maximum Concentration (Cmax) of Dabrafenib Metabolites |
811; 662; 473; 1370; 694; 894 | — |
| SECONDARY Time to Reach Maximum (Peak) Plasma Concentration Following Drug Administration (Tmax) of Dabrafenib and Its Metabolites |
2.00; 2.00; 2.00; 2.00; 2.00; 2.00 | — |
| SECONDARY Elimination Half Life (T½) of Dabrafenib and Its Metabolites |
1.98; 2.85; 2.74; 1.56; 3.03; 2.54 | — |
| SECONDARY Incidence of Treatment Emergent Adverse Events (AEs) in Part 2 (Tumor Specific Expansion) |
0; 1; 0; 0; 0; 0 | — |
| SECONDARY Best Overall Response Based on Investigator Assessment Per Response Assessment in Neuro-Oncology (RANO) Criteria for Low Grade Glioma (LLG) Subjects |
3; 5; 4; 12; 17; 24 | — |
| SECONDARY Best Overall Response Based on Investigator Assessment Per Response Assessment in Neuro-Oncology (RANO) Criteria for High Grade Glioma (HGG) Subjects |
2; 1; 7; 7; 10 | — |
| SECONDARY Effect of Weight on Total Apparent Clearance (CL/F) of Dabrafenib Estimated With a PopPK Model |
0.223 | — |
| SECONDARY Effect of Weight on Volume of Distribution (V/F) of Dabrafenib Estimated With a PopPK Model |
0.593 | — |
| SECONDARY Effect of Weight on Absorption Rate (ka) of Dabrafenib Estimated With a PopPK Model |
NA | — |
| SECONDARY Effect of Weight on Coefficients for Significant Covariates of Dabrafenib Estimated With a PopPK Model |
NA | — |
Eligibility Criteria
Inclusion Criteria
- Written informed consent - a signed informed consent and/or assent (as age appropriate) will be obtained according to institutional guidelines.
- Male or female >=12 months and =50% according to the Karnofsky/Lansky performance status scale (subjects with a performance status of =1000/ microliter (µL), hemoglobin >=8.0 grams (g)/ deciliter (dL) (may receive red blood cell transfusions), platelets >=75,000/µL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment).
- Adequate renal and metabolic function defined as: calculated glomerular filtration rate (eGFR) (Schwartz formula), or radioisotope GFR >=90 milliliters/minutes (mL/min)/1.73 meter square (m^2); or a serum creatinine within the institutional reference range upper limit of normal (for age/gender, if available).
- Adequate liver function defined as: bilirubin (sum of conjugated + unconjugated) =50% by ECHO or greater than institutional lower limit of normal (LLN) by echocardiogram (ECHO) (while not receiving medications for cardiac function), corrected QT using Bazett's (QTcB) interval =grade 2) documented by echocardiogram (NOTE: subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study).
- Subjects with moderate valvular thickening.
- Known, uncontrolled cardiac arrhythmias (except sinus arrhythmia) within the past 24 weeks
- Uncontrolled medical conditions (e.g., diabetes mellitus, hypertension, liver disease or uncontrolled infection), psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol.
- Presence of active GI disease or other condition (e.g., small bowel or large bowel resection) that will interfere significantly with the absorption of drugs.
- Hepatitis B Virus, or Hepatitis C Virus infection (subjects with laboratory evidence of Hepatitis B Virus clearance may be enrolled).
- Pregnant females as determined by positive human chorionic gonadotropin (hCG) test at screening or prior to dosing.
- Lactating females who are actively breast feeding.
Data sourced from ClinicalTrials.gov (NCT01677741). 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.