Clinical trial NCT01164891: A Pharmacokinetic and Metabolism Study of 14C-labeled RO5185426 on Patients With Metastatic Melanoma
Official title: A Phase I, Open-label, Excretion Balance, Pharmacokinetic and Metabolism Study After Single Oral Dose of 14C-labeled RO5185426 in Previously Treated and Untreated Patients With Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malignant Melanoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-07-19
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This open-label, non-randomized study will assess the mass balance, metabolism, routes and rates of elimination as well as efficacy and safety of RO5185426 (RG7204; PLEXXIKON; PLX4032) in previously treated or untreated patients with metastatic melanoma. Patients will receive continuous twice daily oral treatment with RO5185426. On Day 15, a 14C-labeled dose will be administered. Anticipated time on study treatment is until disease progression occurs.


Eligibility criteria: Inclusion Criteria:

* Adult patients, \>/= 18 years of age
* Histologically confirmed metastatic melanoma, surgically incurable and unresectable Stage IIIc or IV (AJCC)
* Prior treatment for metastatic melanoma allowed; \>/= 28 days must be elapsed since previous systemic treatment prior to first administration of study drug
* Positive BRAF V600E mutation result (by Roche CoDx test)
* ECOG performance status 0-1
* Adequate hematologic, renal and liver function
* Body Mass Index (BMI) 18 to 32 kg/m2 inclusive

Exclusion Criteria:

* Active CNS lesions
* History of or known spinal cord compression, or carcinomatous meningitis
* Anticipated or ongoing administration of any anticancer therapies other than those administered in this study
* Refractory nausea or vomiting, or other medical conditions that are capable of altering the absorption, metabolism or elimination of the study drug
* Known clinically significant active infection
* Known HIV positivity or AIDS-related illness, active HBV, or active HCV
* 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
* Clinically significant cardiovascular disease or incident within the 6 months prior to study drug administration
* Patients who have had at least one dose of study drug (RO5185426 or comparator) in a clinical trial that includes RO5185426

Primary outcomes:
measure: Plasma RO5185426 Trough Concentrations on Days 15,16, and 17
timeFrame: Pre-dose on Days 15, 16 and 17
measure: Maximum Plasma Concentration of 14C-labeled RO5185426 (Cmax) in Both Blood and Plasma
timeFrame: 0 hour (prior to evening dose) on Day 14; 0 hour (pre dose), 1, 2, 4, 6, 12, 24, 36, 48, 72, 96, 168, 216, 312 hours post dose on Day 15, and then every 96 hour until recovery criteria met (maximum: 432 hours)
measure: Time to Reach Cmax in Both Blood and Plasma
timeFrame: 0 hour (prior to evening dose) on Day 14; 0 hour (pre dose), 1, 2, 4, 6, 12, 24, 36, 48, 72, 96, 168, 216, 312 hours post dose on Day 15, and then every 96 hour until recovery criteria met (maximum: 432 hours)
measure: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Sample (AUClast) of 14C-RO5185426 in Both Blood and Plasma
timeFrame: 0 hour (prior to evening dose) on Day 14; 0 hour (pre dose), 1, 2, 4, 6, 12, 24, 36, 48, 72, 96, 168, 216, 312 hours post dose on Day 15, and then every 96 hour until recovery criteria met (maximum: 432 hours)
measure: Half-life of 14C-labeled RO5185426 in Both Blood and Plasma
timeFrame: 0 hour (prior to evening dose) on Day 14; 0 hour (pre dose), 1, 2, 4, 6, 12, 24, 36, 48, 72, 96, 168, 216, 312 hours post dose on Day 15, and then every 96 hour until recovery criteria met (maximum: 432 hours)
measure: AUC Ratio of Blood:Plasma 14C-labeled RO5185426
timeFrame: 0 hour (prior to evening dose) on Day 14; 0 hour (pre dose), 1, 2, 4, 6, 12, 24, 36, 48, 72, 96, 168, 216, 312 hours post dose on Day 15, and then every 96 hour until recovery criteria met (maximum: 432 hours)
measure: 14C-labeled RO5185426 Recovery: Percentage of Dose Excreted in Feces and Urine
timeFrame: Urine:0 hour (pre dose),in quantitative fraction(0-6,6-12,12-24 hours) post dose on Day 15,during 24 hour interval thereafter;Feces:From Day 14 upto pre dose on Day 15,during 24 hour interval post dose until recovery criterion;(maximum:432 hours for both)
measure: Percentage of Total Integrated Radioactivity in Plasma of 14C-labeled RO5185426 and 14C-labeled Metabolite
timeFrame: 4+6 hours, 12 +24 hours, 36+48 hours post dose on Day 15
measure: Plasma 14C-labeled RO5185426 and 14C-labeled Metabolite Levels
timeFrame: 4+6 hours, 12 +24 hours, 36+48 hours post dose on Day 15
measure: Percentage of Total Integrated Radioactivity in Feces of 14C-labeled RO5185426 and 14C-labeled Metabolite
timeFrame: 0-24 + 24-48 hours, 48-72 + 72-96 hours post dose on Day 15
measure: Percentage of Total Dose in 14C-labeled RO5185426 and 14C-labeled Metabolite in Pooled Fecal Samples
timeFrame: 0-24 + 24-48 hours, 48-72 + 72-96 hours post dose on Day 15
measure: Percentage of Total Integrated Radioactivity in Urine of 14C-labeled RO5185426 and 14C-labeled Metabolite
timeFrame: 0 up to 96 hours post dose on Day 15
measure: Percentage of Total Dose in 14C-labeled RO5185426 and 14C-labeled Metabolite in Pooled Urine Samples
timeFrame: 0 up to 96 hours post dose on Day 15
Secondary outcomes:
measure: Number of Participants With a Response by Confirmed Best Overall Response
timeFrame: From Baseline then Day 1 of Cycle 3 thereafter, Day 1 of every other cycle (every 2 months) until disease progression, withdrawal from study or death (maximum 841 days)
measure: Overall Survival
timeFrame: From Baseline then Day 1 of Cycle 3 thereafter, Day 1 of every other cycle (every 2 months) until death (maximum 841 days)
Other outcomes:
Locations:
city: Zürich
country: Switzerland
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: