Phase 1
Completed N=25
A Pharmacokinetic Study of RO5185426 in Combination With a Drug Cocktail in Patients With Metastatic Melanoma
Source: ClinicalTrials.gov NCT01001299 ↗Enrolled (actual)
25
Serious AEs
48.0%
Results posted
Oct 2015
Primary outcomePrimary: 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 — 2.56; 1.47; 0.61; 1.13 ratio
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
2.56; 1.47; 0.61; 1.13; 1.18 | — |
| PRIMARY Geometric Mean Ratio of Maximum Plasma Concentration (Cmax) of Probe Parent Drugs |
1.05; 1.36; 0.65; 1.17; 1.00 | — |
| PRIMARY Geometric Mean Ratio of AUC(0-last) and Cmax of Metabolites of Probe Parent Drugs |
1.15; 0.60; 1.46; 1.21; 1.34; 1.23 | — |
| PRIMARY AUC(0-last) and Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC[0-inf]) of Probe Parent Drugs and Their Metabolites on Day 1 |
56350.1; 58337.5; 45584.3; 47589.5; 14964.5; 17832.5 | — |
| PRIMARY AUC(0-last) and AUC(0-inf) of Probe Parent Drugs and Their Metabolites on Day 20 |
140991.9; 161490.6; 51344.3; 55060.5; 17804.4; 22233.3 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time Zero to 8, 12, and 24 Hours (AUC[0-8], AUC[0-12], AUC[0-24]) of Vemurafenib |
422; 601; 1176 | — |
| PRIMARY Cmax of Probe Parent Drugs and Their Metabolites on Day 1 |
4768.9; 1839.1; 469.4; 913.7; 331.3; 3.38 | — |
| PRIMARY Cmax of Probe Parent Drugs and Their Metabolites on Day 20 |
4990.5; 1154.9; 468.3; 945.8; 348.7; 4.19 | — |
| PRIMARY Cmax of Vemurafenib |
61.7 | — |
| PRIMARY Time to Reach Maximum Plasma Concentration (Tmax) of Probe Parent Drugs and Their Metabolites on Day 1 |
1.00; 8.00; 3.00; 3.00; 3.00; 1.50 | — |
| PRIMARY Tmax of Probe Parent Drugs and Their Metabolites on Day 20 |
2.00; 24.00; 3.00; 2.5; 3.00; 1.50 | — |
| PRIMARY Tmax of Vemurafenib |
3.10 | — |
| PRIMARY Trough Plasma Concentration (Cmin) of Vemurafenib |
54.5 | — |
| PRIMARY Apparent Elimination Half-Life in Plasma (t1/2) of Probe Parent Drugs and Their Metabolites on Day 1 |
6.7; 18.5; 42.3; 2.0; 2.6; 9.08 | — |
| PRIMARY t1/2 of Probe Parent Drugs and Their Metabolites on Day 20 |
20.6; 35.3; 47.4; 2.6; 3.2; 8.24 | — |
| PRIMARY Apparent Plasma Clearance (CL/F) of Probe Parent Drugs on Day 1 |
4.2; 622.4; 0.035; 4108.04; 72199.55 | — |
| PRIMARY CL/F of Probe Parent Drugs on Day 20 |
1.6; 513.5; 0.027; 2921.59; 125436.51 | — |
| SECONDARY Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) |
44 | — |
| SECONDARY Duration of Response |
— | — |
| SECONDARY Time to Response |
— | — |
| SECONDARY Progression-Free Survival (PFS) |
— | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT01001299). 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.