Phase 1
N=52
A Pharmacokinetic/Pharmacodynamic Study of RO5185426 in Previously Treated Patients With Metastatic Melanoma
Malignant Melanoma
Bottom Line
View on ClinicalTrials.gov: NCT01107418 ↗Enrolled (actual)
52
Serious AEs
40.4%
Results posted
Aug 2015
Primary outcome: Primary: Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1 — 8.3; 13.8; 21.9; 27.0 micrograms*hour/milliliter (mcg*h/mL)
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
- Feb 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1 |
8.3; 13.8; 21.9; 27.0 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 1 |
40.9; 62.4; 111.6; 130.6 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 1 |
1.9; 2.6; 4.4; 4.8 | — |
| PRIMARY Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 1 |
4.0; 4.0; 5.0; 5.0 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 9 |
102.1; 180.0; 301.2; 329.0 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 9 |
15.4; 28.9; 45.9; 53.2 | — |
| PRIMARY Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 9 |
2.0; 2.0; 0.0; 1.8 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 15 |
117.8; 233.8; 343.3; 392.2 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 15 |
317.7; 598.8; 1003.7; 1126.0 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC[0-168h]) of Vemurafenib on Day 15 |
920.3; 2243.5; 3127.1; 3530.3 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15 |
17.2; 35.4; 52.7; 61.4 | — |
| PRIMARY Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 15 |
4.0; 2.3; 2.0; 2.0 | — |
| PRIMARY Apparent Clearance (CL/F) of Vemurafenib on Day 15 |
0.3; 0.8; 0.4; 0.3 | — |
| PRIMARY Terminal Elimination Half-Life (t1/2) of Vemurafenib on Day 15 |
31.5; 38.4; 34.9; 34.1 | — |
| PRIMARY Accumulation Ratio of Vemurafenib on Day 15 |
24.9; 23.3; 18.8; 23.2 | — |
| SECONDARY Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) |
49 | — |
| SECONDARY Overall Survival (OS) |
— | — |
Summary
This open-label study will assess the pharmacokinetics, efficacy and safety of RO5185426 administered as 240mg tablets in previously treated patients with metastatic melanoma. Patients will be randomized to receive one of four dose-levels of RO5185426 [RG7204; PLEXXIKON; PLX4032] orally twice daily on days 1 to 15 (morning dose). Starting on day 22, treatment with RO5185426 may be resumed at a dose of 960 mg twice daily and continued until disease progression. Target sample size is <100 patients.
Eligibility Criteria
Inclusion Criteria
- adult patients, >/=18 years of age
- histologically confirmed metastatic melanoma, stage IIIc or IV (AJCC)
- failure of at least one prior standard of care regimen
- positive for BRAF V600E mutation (by Roche CoDx BRAF mutation assay)
- ECOG performance status 0 or 1
- adequate hematologic, renal and liver function
Exclusion Criteria
- active CNS lesions on CT/MRI within 28 days prior to enrollment
- history of spinal cord compression o carcinomatous meningitis
- anticipated or ongoing anti-cancer therapies other than those administered in this study
- previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor
- severe cardiovascular disease within 6 months prior to 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
Data sourced from ClinicalTrials.gov (NCT01107418). 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.