Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Continuous oral dosing b.i.d. , on Day 15 a C isotope labeled dose will be administered

RO5185426

Clinical Trials

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.

A Pharmacokinetic and Metabolism Study of 14C-labeled RO5185426 on Patients With Metastatic Melanoma

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

Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). 14C-labeled RO5185426 given was equivalent to ≤1 millisieverts (mSv).

Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments).

Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). 14C-labeled RO5185426 given was equivalent to ≤1mSv.

Urinary and fecal samples were analyze for the percentage dose recovered as total radioactivity. The radioactivity was determined on a Packard liquid scintillation counter. Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments).

Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). Plasma samples were pooled over three time intervals for this analysis based on available radioactive counts (4 + 6 hours, 12 + 24 hours, and 36 + 48 hours). Radioactivity was measured in terms of region of interest by high performance liquid chromatography. The radiolabelled components in each chromatogram were evaluated to determine retention times and peak area values. Data for 14C-labeled RO5185426 and 14C-labeled metabolite (mono-hydroxy) are reported.

Collection of samples for radioactivity continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48 hour interval assessments). Plasma samples were pooled over three time intervals for this analysis based on available radioactive counts (4 + 6 hours, 12 + 24 hours, and 36 + 48 hours). The concentrations were measured in nanogram equivalent per gram which was calculated based on ratio of dosed radioactivity and the last dose of RO5185426. The concentration values represented the drug portion of the last dose. Data for 14C-labeled RO5185426 and 14C-labeled metabolite (mono-hydroxy) are reported.

Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). Fecal samples were pooled over two time intervals for this analysis (0-24 + 24-48 hours, 48-72 + 72-96 hours). Radioactivity was measured in terms of region of interest by high performance liquid chromatography. The radiolabelled components in each chromatogram were evaluated to determine retention times and peak area values. Data for 14C-labeled RO5185426 and 14C-labeled metabolites (glucosylation, mono-hydroxy, and glucuronide) are reported.

Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). Fecal samples were pooled over 2 time intervals (0-24 + 24-48 hours, 48-72 + 72-96 hours) for measurement of 14C-labeled RO5185426 and 14C-labeled metabolites (glucosylation, mono-hydroxy, glucuronide) levels.

Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). Urine samples were pooled over period of 96 hours (pool of 0-6 + 6-12 + 12-24 + 24-48 + 48-72 + 72-96 hour samples), Radioactivity was measured in terms of region of interest by high performance liquid chromatography. The radiolabelled components in each chromatogram were evaluated to determine retention times and peak area values. Data for 14C-labeled RO5185426 and 14C-labeled metabolites (2 unknown metabolites, glucosylation, mono-hydroxy) are reported.

Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). Urine samples were pooled over period of 96 hours (pool of 0-6 + 6-12 + 12-24 + 24-48 + 48-72 + 72-96 hour samples). Data for parent drug (RO5185426) and metabolites (2 unknown metabolites, glucosylation, mono-hydroxy) are reported.

Best overall response (according to Response Evaluation Criteria In Solid Tumors 1.1 criteria) was defined as best response recorded from start of treatment until disease progression which included complete response (CR) or partial response (PR) that had been confirmed by second tumor assessment no less than (\<) 4 weeks after criteria for response were first met. Confirmed CR: disappearance of all target and non-target lesions; no new lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 millimeters (mm). Confirmed PR: at least 30% decrease in sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Disease progression: at least 20% increase in sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.

Overall survival was defined as the time from the date of first treatment to the date of death, regardless of the cause of death.

Hoffmann-La Roche

Safety population included all participants who received at least 1 dose of study drug.

Participants received non-labeled RO5185426 film-coated tablets 960 mg orally BID from Day 1 to Day 14. On Day 15, participants received a single dose of 960 mg RO5185426 with a maximum of 2.56 millibecquerel (69.2 microcurie) of 14C RO5185426. After Day 15, participants received non-labeled RO5185426 film-coated tablets 960 mg orally BID until the development of progressive disease, unacceptable toxicity, consent withdrawal, death, lost to follow-up or any other criteria for removal as determined by the investigator.

14C-labeled RO5185426

Age, Continuous

Sex: Female, Male

Medical Communications

Day 15

Day 16

Day 17

Pharmacokinetic (PK) Analysis Population: participants from whom the level of radioactivity recovered from excreta (urine and feces) was ≤ 1% of the radioactivity in the administered dose between any two successive 48-hour interval assessments.

Plasma RO5185426 Trough Concentrations on Days 15,16, and 17

Number of Participants With a Response by Confirmed Best Overall Response

The data was not collected, as planned, due to small number of participants enrolled in the study.

Overall Survival

Blood

Plasma

PK Analysis Population. Number of participants analyzed = participants with measurable data for this outcome.

Maximum Plasma Concentration of 14C-labeled RO5185426 (Cmax) in Both Blood and Plasma

Time to Reach Cmax in Both Blood and Plasma

Area Under the Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Sample (AUClast) of 14C-RO5185426 in Both Blood and Plasma

Half-life of 14C-labeled RO5185426 in Both Blood and Plasma

PK Analysis Population. Number of participants analysed = participants with measurable data for this outcome.

AUC Ratio of Blood:Plasma 14C-labeled RO5185426

Percent Dose Recovery in Feces

Percent Dose Recovery in Urine

Percent Dose Total Recovery (Feces and Urine)

PK Analysis Population. One participant was excluded in the analysis because of contamination of urine sample with feces.

14C-labeled RO5185426 Recovery: Percentage of Dose Excreted in Feces and Urine

RO5185426: 4 + 6 hours

RO5185426: 12 + 24 hours

RO5185426: 36 + 48 hours

Mono-hydroxy Metabolite: 4 + 6 hours

Mono-hydroxy Metabolite: 12 + 24 hours

Mono-hydroxy Metabolite: 36 + 48 hours

Percentage of Total Integrated Radioactivity in Plasma of 14C-labeled RO5185426 and 14C-labeled Metabolite

Plasma 14C-labeled RO5185426 and 14C-labeled Metabolite Levels

RO5185426: 0-24 + 24-48 hours

RO5185426: 48-72 + 72-96 hours

Glucosylation: 0-24 + 24-48 hours

Glucosylation: 48-72 + 72-96 hours

Mono-hydroxy: 0-24 + 24-48 hours

Mono-hydroxy: 48-72 + 72-96 hours

Glucuronide: 0-24 + 24-48 hours

Glucuronide: 48-72 + 72-96 hours

Participants received non-labeled RO5185426 film-coated tablets 960 mg orally BID from Day 1 to Day 14. On Day 15 participants received a single dose of 960 mg RO5185426 with a maximum of 2.56 millibecquerel (69.2 microcurie) of 14C RO5185426. After Day 15, participants received non-labeled RO5185426 film-coated tablets 960 mg orally BID until the development of progressive disease, unacceptable toxicity, consent withdrawal, death, lost to follow-up or any other criteria for removal as determined by the investigator.

Percentage of Total Integrated Radioactivity in Feces of 14C-labeled RO5185426 and 14C-labeled Metabolite

Percentage of Total Dose in 14C-labeled RO5185426 and 14C-labeled Metabolite in Pooled Fecal Samples

Unknown Metabolite 1

Unknown Metabolite 2

Glucosylation

Mono-hydroxy

Percentage of Total Integrated Radioactivity in Urine of 14C-labeled RO5185426 and 14C-labeled Metabolite

Percentage of Total Dose in 14C-labeled RO5185426 and 14C-labeled Metabolite in Pooled Urine Samples

Participants received non-labeled RO5185426 film-coated tablets 960 milligrams (mg) orally two times daily (BID) from Day 1 to Day 14. On Day 15, participants received a single dose of 960 mg RO5185426 with a maximum of 2.56 millibecquerel (69.2 microcurie) of 14C RO5185426. After Day 15, participants received non-labeled RO5185426 film-coated tablets 960 mg orally BID until the development of progressive disease, unacceptable toxicity, consent withdrawal, death, lost to follow-up or any other criteria for removal as determined by the investigator.

Spots Global Cancer Trial Database for A Pharmacokinetic and Metabolism Study of 14C-labeled RO5185426 on Patients With Metastatic Melanoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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