Clinical trial · Interventional
A Pharmacokinetic Study of RO5185426 in Combination With a Drug Cocktail in Patients With Metastatic Melanoma
A Multi-center, Open-label, Study to Investigate the Pharmacokinetic Interaction of RO5185426 With a "Cocktail" of Five Probe Drugs for CYP450 Dependent Metabolism in Patients With Previously Treated and Untreated Metastatic Melanoma
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This open-label single-arm study will evaluate the effect of RO5185426 \[RG7204; PLEXXIKON: PLX4032\] on the pharmacokinetics of five CYP450 substrates (caffeine, warfarin + vitamin K, omeprazole, dextromethorphan, midazolam) administered as a drug cocktail to patients with metastatic melanoma. The study will also evaluate efficacy and safety of RO5185426. On day 1, patients will receive the drug cocktail. On days 6 to 19, patients will receive RO5185426 twice daily. On day 20, patients will receive RO5185426 and the drug cocktail and on days 21 to 25, patients will receive RO5185426. Assessments will be made at regular intervals during the dosing periods and at follow-up. Patients may continue on study treatment (RO5185426) until the development of progressive disease or unacceptable toxicity. Target sample size \<50.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Malignant Melanoma | Melanoma | ALIAS | 0.90 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Drug cocktail | Drug | — | UNRESOLVED |
| RO5185426 | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Single arm
- interventionNames
- Drug: Drug cocktail
- Drug: RO5185426
Primary outcomes (17)
- measure
- Geometric Mean Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Observed Sampling Time (AUC[0-last]) of Probe Parent Drugs
- timeFrame
- Day 1, 20: 0, 1, 3, 4, 6, 8, 24 hours, additionally for caffeine 0.5, 1.5, 2, 12, 18, 48, 72, 96, 120,dextromethorphan 0.5, 1.5, 2, 12, 18, 48,midazolam 0.08, 0.25, 0.5, 0.75, 2, 10,omeprazole 0.5, 1.5, 2, 2.5, 12, 18,S-warfarin 12, 48, 72, 96, 120 hours
- description
- AUC(0-last) was defined as the area under the plasma concentration-time curve calculated using the linear trapezoidal rule from time zero to the last observed sampling time. To assess the potential for drug-drug interactions, the geometric mean ratios and corresponding 90 percent (%) confidence interval (CI) of AUC(0-last) of parent probe drug before (Day 1) and after treatment with vemurafenib (Day 20) was calculated. Ratio and corresponding 90% CI of AUC(0-last) (Day 20/Day 1) for each of the 5 probe drugs is reported.
- measure
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Adult patient \>/= 18 years of age * Malignant melanoma (Stage IV, AJCC) * Patients who are treatment-naive or have received prior systemic treatments for metastatic melanoma. Time elapsed between previous treatment for metastatic disease and first administration of study drug must be at least 28 days * Positive tested for BRAF mutation * Patients must not be poor metabolizers of CYP450 enzymes 2C9, 2C19, or 2D6 as determined by genotyping * Measurable disease by RECIST criteria * Negative pregnancy test; for fertile men and women, effective contraception during treatment and for 6 months after completion Exclusion Criteria: * Active CNS lesions on CT/MRI within 28 days prior to enrollment * History of known spinal cord compression, or carcinomatous meningitis * Severe cardiovascular disease within 6 months prior to study
References
Publications (1)
- DERIVEDSu F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT, Chapman PB, Kim MJ, Hayward R, Martin M, Yang H, Wang Q, Hilton H, Hang JS, Noe J, Lambros M, Geyer F, Dhomen N, Niculescu-Duvaz I, Zambon A, Niculescu-Duvaz D, Preece N, Robert L, Otte NJ, Mok S, Kee D, Ma Y, Zhang C, Habets G, Burton EA, Wong B, Nguyen H, Kockx M, Andries L, Lestini B, Nolop KB, Lee RJ, Joe AK, Troy JL, Gonzalez R, Hutson TE, Puzanov I, Chmielowski B, Springer CJ, McArthur GA, Sosman JA, Lo RS, Ribas A, Marais R. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012 Jan 19;366(3):207-15. doi: 10.1056/NEJMoa1105358. PMID 22256804