Back to resultsA Pharmacokinetic/Pharmacodynamic Study of RO5185426 in Previously Treated Patients With Metastatic Melanoma
Primary Purpose
Malignant Melanoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
RO5185426
RO5185426
RO5185426
RO5185426
RO5185426
Sponsored by
About this trial
This is an interventional treatment trial for Malignant Melanoma
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
1
2
3
4
Arm Description
Outcomes
Primary Outcome Measures
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 1
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 1
Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 1
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 9
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 9
Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 9
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 15
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 15
Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC[0-168h]) of Vemurafenib on Day 15
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15
Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 15
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.
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).
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.
Secondary Outcome Measures
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01107418
Brief Title
A Pharmacokinetic/Pharmacodynamic Study of RO5185426 in Previously Treated Patients With Metastatic Melanoma
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
May 2010 (undefined)
Primary Completion Date
February 2013 (Actual)
Study Completion Date
February 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Title
2
Arm Type
Experimental
Arm Title
3
Arm Type
Experimental
Arm Title
4
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
RO5185426
Intervention Description
dosage b) orally twice daily, days 1-15 (morning dose)
Intervention Type
Drug
Intervention Name(s)
RO5185426
Intervention Description
dosage c) orally twice daily, days 1-15 (morning dose)
Intervention Type
Drug
Intervention Name(s)
RO5185426
Intervention Description
dosage d) orally twice daily, days 1-15 (morning dose)
Intervention Type
Drug
Intervention Name(s)
RO5185426
Intervention Description
960 mg orally twice daily, from day 22 onward
Intervention Type
Drug
Intervention Name(s)
RO5185426
Intervention Description
dosage a) orally twice daily, days 1-15 (morning dose)
Primary Outcome Measure Information:
Title
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1
Time Frame
Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
Title
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 1
Time Frame
Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 1
Title
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 1
Time Frame
Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
Title
Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 1
Time Frame
Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
Title
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 9
Time Frame
Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
Title
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 9
Time Frame
Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
Title
Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 9
Time Frame
Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
Title
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 15
Time Frame
Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 15
Title
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 15
Time Frame
Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 15
Title
Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC[0-168h]) of Vemurafenib on Day 15
Time Frame
Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Title
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15
Time Frame
Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Title
Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 15
Time Frame
Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Title
Apparent Clearance (CL/F) of Vemurafenib on Day 15
Description
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.
Time Frame
Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Title
Terminal Elimination Half-Life (t1/2) of Vemurafenib on Day 15
Description
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).
Time Frame
Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Title
Accumulation Ratio of Vemurafenib on Day 15
Description
Accumulation ratio was calculated as, AUC(0-8) on Day 15 divided by AUC(0-8) on Day 1.
Time Frame
Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 and 15
Secondary Outcome Measure Information:
Title
Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR)
Description
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.
Time Frame
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)
Title
Overall Survival (OS)
Description
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.
Time Frame
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510-3289
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
City
Park Ridge
State/Province
Illinois
ZIP/Postal Code
60068
Country
United States
City
Sioux City
State/Province
Iowa
ZIP/Postal Code
51101
Country
United States
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43219
Country
United States
City
East Providence
State/Province
Rhode Island
ZIP/Postal Code
02915
Country
United States
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3181
Country
Australia
12. IPD Sharing Statement
Citations:
PubMed Identifier
24983357
Citation
Frederick DT, Salas Fragomeni RA, Schalck A, Ferreiro-Neira I, Hoff T, Cooper ZA, Haq R, Panka DJ, Kwong LN, Davies MA, Cusack JC, Flaherty KT, Fisher DE, Mier JW, Wargo JA, Sullivan RJ. Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics. PLoS One. 2014 Jul 1;9(7):e101286. doi: 10.1371/journal.pone.0101286. eCollection 2014.
Results Reference
derived
PubMed Identifier
23457002
Citation
Lacouture ME, Duvic M, Hauschild A, Prieto VG, Robert C, Schadendorf D, Kim CC, McCormack CJ, Myskowski PL, Spleiss O, Trunzer K, Su F, Nelson B, Nolop KB, Grippo JF, Lee RJ, Klimek MJ, Troy JL, Joe AK. Analysis of dermatologic events in vemurafenib-treated patients with melanoma. Oncologist. 2013;18(3):314-22. doi: 10.1634/theoncologist.2012-0333. Epub 2013 Mar 1.
Results Reference
derived
Learn more about this trial
A Pharmacokinetic/Pharmacodynamic Study of RO5185426 in Previously Treated Patients With Metastatic Melanoma
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