Phase 1
N=7
A Pharmacokinetic and Metabolism Study of 14C-labeled RO5185426 on Patients With Metastatic Melanoma
Malignant Melanoma
Bottom Line
View on ClinicalTrials.gov: NCT01164891 ↗Enrolled (actual)
7
Serious AEs
42.9%
Results posted
Dec 2015
Primary outcome: Primary: Plasma RO5185426 Trough Concentrations on Days 15,16, and 17 — 61.1; 67.7; 61.5 micrograms per milliliter
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- RO5185426 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Dec 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Plasma RO5185426 Trough Concentrations on Days 15,16, and 17 |
61.1; 67.7; 61.5 | — |
| PRIMARY Maximum Plasma Concentration of 14C-labeled RO5185426 (Cmax) in Both Blood and Plasma |
5.25; 7.83 | — |
| PRIMARY Time to Reach Cmax in Both Blood and Plasma |
4.1; 4.1 | — |
| PRIMARY Area Under the Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Sample (AUClast) of 14C-RO5185426 in Both Blood and Plasma |
456.0; 633.0 | — |
| PRIMARY Half-life of 14C-labeled RO5185426 in Both Blood and Plasma |
84.4; 71.1 | — |
| PRIMARY AUC Ratio of Blood:Plasma 14C-labeled RO5185426 |
0.72 | — |
| PRIMARY 14C-labeled RO5185426 Recovery: Percentage of Dose Excreted in Feces and Urine |
94.05; 0.97; 95.02 | — |
| PRIMARY Percentage of Total Integrated Radioactivity in Plasma of 14C-labeled RO5185426 and 14C-labeled Metabolite |
99.46; 95.93; 96.03; 0.54; 4.07; 3.97 | — |
| PRIMARY Plasma 14C-labeled RO5185426 and 14C-labeled Metabolite Levels |
6122; 6139; 4710; 57; 321; 238 | — |
| PRIMARY Percentage of Total Integrated Radioactivity in Feces of 14C-labeled RO5185426 and 14C-labeled Metabolite |
94.19; 55.52; 2.58; 18.83; 0.15; 13.71 | — |
| PRIMARY Percentage of Total Dose in 14C-labeled RO5185426 and 14C-labeled Metabolite in Pooled Fecal Samples |
37.49; 17.10; 0.97; 5.04; 0.11; 3.30 | — |
| PRIMARY Percentage of Total Integrated Radioactivity in Urine of 14C-labeled RO5185426 and 14C-labeled Metabolite |
32.38; 4.56; 25.44; 30.22; 7.41 | — |
| PRIMARY Percentage of Total Dose in 14C-labeled RO5185426 and 14C-labeled Metabolite in Pooled Urine Samples |
1.03; 0.04; 0.17; 0.24; 0.05 | — |
| SECONDARY Number of Participants With a Response by Confirmed Best Overall Response |
4 | — |
| SECONDARY Overall Survival |
— | — |
Summary
This open-label, non-randomized study will assess the mass balance, metabolism, routes and rates of elimination as well as efficacy and safety of RO5185426 (RG7204; PLEXXIKON; PLX4032) in previously treated or untreated patients with metastatic melanoma. Patients will receive continuous twice daily oral treatment with RO5185426. On Day 15, a 14C-labeled dose will be administered. Anticipated time on study treatment is until disease progression occurs.
Eligibility Criteria
Inclusion Criteria
- Adult patients, >/= 18 years of age
- Histologically confirmed metastatic melanoma, surgically incurable and unresectable Stage IIIc or IV (AJCC)
- Prior treatment for metastatic melanoma allowed; >/= 28 days must be elapsed since previous systemic treatment prior to first administration of study drug
- Positive BRAF V600E mutation result (by Roche CoDx test)
- ECOG performance status 0-1
- Adequate hematologic, renal and liver function
- Body Mass Index (BMI) 18 to 32 kg/m2 inclusive
Exclusion Criteria
- Active CNS lesions
- History of or known spinal cord compression, or carcinomatous meningitis
- Anticipated or ongoing administration of any anticancer therapies other than those administered in this study
- Refractory nausea or vomiting, or other medical conditions that are capable of altering the absorption, metabolism or elimination of the study drug
- Known clinically significant active infection
- Known HIV positivity or AIDS-related illness, active HBV, or active HCV
- Previous malignancy within the past 5 years, except for basal or squamous cell carcinoma of the skin, melanoma in situ, and carcinoma in situ of the cervix
- Clinically significant cardiovascular disease or incident within the 6 months prior to study drug administration
- Patients who have had at least one dose of study drug (RO5185426 or comparator) in a clinical trial that includes RO5185426
Data sourced from ClinicalTrials.gov (NCT01164891). 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.