A Pharmacokinetic/Pharmacodynamic Study of RO5185426 in Previously Treated Patients With Metastatic Melanoma

Malignant Melanoma Clinical Trial

Official title:

A Phase I, Randomized, Open-label, Multi-center, Multiple Dose Study to Investigate the Pharmacokinetics and Pharmacodynamics of RO5185426 Administered as 240 mg Tablets to Previously Treated BRAF V600E Positive Metastatic Melanoma Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01107418
• Other study ID #: NP25163
• Status: Completed
• Phase: Phase 1
• First received: April 12, 2010
• Last updated: July 29, 2015
• Start date: May 2010
• Est. completion date: February 2013

Study information

• Verified date: July 2015
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malignant Melanoma
• Melanoma

Intervention

Drug:
• RO5185426
dosage b) orally twice daily, days 1-15 (morning dose)
• RO5185426
dosage c) orally twice daily, days 1-15 (morning dose)
• RO5185426
dosage d) orally twice daily, days 1-15 (morning dose)
• RO5185426
960 mg orally twice daily, from day 22 onward
• RO5185426
dosage a) orally twice daily, days 1-15 (morning dose)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1		Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1	No
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 1		Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 1	No
Primary	Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 1		Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1	No
Primary	Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 1		Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1	No
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 9		Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9	No
Primary	Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 9		Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9	No
Primary	Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 9		Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9	No
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 15		Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 15	No
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 15		Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 15	No
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC[0-168h]) of Vemurafenib on Day 15		Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15	No
Primary	Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15		Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15	No
Primary	Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 15		Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15	No
Primary	Apparent Clearance (CL/F) of Vemurafenib on Day 15	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.	Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15	No
Primary	Terminal Elimination Half-Life (t1/2) of Vemurafenib on Day 15	Time measured for vemurafenib plasma concentrations to decrease by one-half (t1/2) was calculated as 0.693 divided by apparent first-order terminal elimination rate constant (0.693/kel).	Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15	No
Primary	Accumulation Ratio of Vemurafenib on Day 15	Accumulation ratio was calculated as, AUC(0-8) on Day 15 divided by AUC(0-8) on Day 1.	Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 and 15	No
Secondary	Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR)	Confirmed best overall response was defined as having best objective response as CR or PR, as assessed by investigator and confirmed at least 28 days after initial response. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) were required to demonstrate a reduction to normal (short axis less than [<] 10 millimeters [mm]). PR was defined as a 30 percent (%) decrease in the sum of the diameters of the target lesions taking as a reference the baseline sum diameter. Percentage of participants with best overall response of confirmed CR or PR are reported.	Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13)	No
Secondary	Overall Survival (OS)	OS was defined as the time, in months, from the date of the first study drug administration to the date of death, regardless of the cause of death.	Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13)	No