Phase 1
Completed N=16
A Study of the Effect of Food on the Pharmacokinetics of Single Dose RO5185426 And the Safety And Efficacy of Continuous Administration in Patients With BRAF V600E Mutation-Positive Metastatic Melanoma
Source: ClinicalTrials.gov NCT01264380 ↗Enrolled (actual)
16
Serious AEs
18.8%
Results posted
Dec 2015
Primary outcomePrimary: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC [0-inf]) in the Fasted and Fed States — 115; 351 micrograms*hour per milliliter (µg*h/mL)
Summary
This randomized, open-label, two period crossover study will evaluate the effect of food on the pharmacokinetics of a single dose of RO5185426 and the efficacy and safety of continuous administration in patients with BRAF V600E mutation-positive metastatic melanoma. Patients will be randomized to receive in a crossover design single oral doses of RO5185426 with or without food, with a 10-day washout period between doses. Following the crossover periods, patients will receive RO5185426 orally twice daily on a continuous basis until disease progression or unacceptable toxicity occurs.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC [0-inf]) in the Fasted and Fed States |
115; 351 | — |
| PRIMARY Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Sample With Last Measurable Concentration (AUC[0-last]) in the Fasted and Fed States |
94.3; 320 | — |
| PRIMARY Maximal Observed Plasma Concentration (Cmax) in the Fasted and Fed States |
3.48; 7.38 | — |
| PRIMARY Minimum Observed (Trough) Plasma Concentration (Cmin) in the Fasted and Fed States |
NA; NA | — |
| PRIMARY Time to Reach Maximal Plasma Concentration (Tmax) in the Fasted and Fed States |
4; 7.51 | — |
| PRIMARY Terminal Elimination Half-Life (t1/2) in the Fasted and Fed States |
24.6; 26.0 | — |
| PRIMARY Apparent First-order Terminal Elimination Rate Constant (Kel) in the Fasted and Fed States |
0.04; 0.04 | — |
| SECONDARY Percentage of Participants With Best Objective Response (BOR) as Complete Response (CR) or Partial Response (PR) |
64.3 | — |
| SECONDARY Overall Survival (OS) |
— | — |
Eligibility Criteria
Inclusion Criteria
- Adult patients, >/= 18 years of age
- Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer)
- Positive BRAF V600E mutation result determined by Cobas 4800 BRAF V600 Mutation Test
- Previously treated patients must have failed at least one prior treatment regimen; if patients have received prior systemic treatments for metastatic melanoma, the time elapsed from previous therapy must be >/= 28 days; patients must have recovered fully from toxicities of all prior therapy
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Evaluable disease (measurable for disease progression according to RECIST criteria)
- Adequate hematological, renal and liver function
Exclusion Criteria
- Active CNS lesions
- History of or known spinal cord compression or carcinomatous meningitis
- Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study
- 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
- Previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor
- Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of any type of gastrointestinal surgery that would preclude adequate absorption of study drug
Data sourced from ClinicalTrials.gov (NCT01264380). 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.