- ICH GCP
- Register voor klinische proeven in de VS.
- Klinische proef NCT00467779
Study of Cobimetinib in Participants With Solid Tumors
A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of GDC-0973/XL518 Administered Orally Daily to Subjects With Solid Tumors
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
-
-
California
-
Los Angeles, California, Verenigde Staten, 90095
-
Stanford, California, Verenigde Staten, 94305-5821
-
-
Michigan
-
Detroit, Michigan, Verenigde Staten, 48201
-
-
New York
-
Buffalo, New York, Verenigde Staten, 14263
-
-
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- Histologically confirmed solid tumor that is metastatic or unresectable, and for which standard curative or palliative measures do not exist or are no longer effective, and there are no known therapies to prolong survival
- Disease that is measurable according to Response Evaluation Criteria in Solid Tumors (RECIST)
- Adequate organ and marrow function
- Sexually active participants must use medically acceptable methods of contraception during the course of the study and at least 11 days after the last dose of study treatment
- Female participants of childbearing potential must have a negative serum pregnancy test at screening
- No other history of/or ongoing malignancy that would potentially interfere with the interpretation of the pharmacodynamic or efficacy assays
Exclusion Criteria:
- Anticancer treatment (e.g., chemotherapy, radiotherapy, cytokines, or hormones) within 28 days (6 weeks for nitrosoureas or mitomycin C, or 14 days for hormonal therapy or kinase inhibitors) before the first dose of study drug
- The participant has not recovered to Grade </=1 from adverse events (AEs) or to within 10% of baseline values due to investigational or other agents administered more than 28 days prior to study enrollment
- The participant has received another investigational agent within 28 days of the first dose of study drug
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, diabetes, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
- The participant is pregnant or breastfeeding
- The participant is known to be positive for the human immunodeficiency virus (HIV)
- Allergy or hypersensitivity to components of the cobimetinib formulation
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
---|---|
Experimenteel: Stage 1: Cobimetinib Dose Escalation (21/7 Schedule)
Participants will receive cobimetinib (GDC-0973/XL518) at the starting dose of 0.05 mg/kg via solution or capsule, once daily for Days 1-21 of each 28-day cycle (21 days on drug followed by 7 days off treatment [21/7 schedule]).
Treatment will continue until progressive disease (PD) or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
|
Repeating oral dose
Andere namen:
|
Experimenteel: Stage 1A: Cobimetinib Dose Escalation (14/14 Schedule)
Participants will receive cobimetinib at the starting dose of 60 mg via solution or capsule, once daily for Days 1-14 of each 28-day cycle (14 days on drug followed by 14 days off treatment [14/14 schedule]).
Treatment will continue until progressive disease (PD) or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
|
Repeating oral dose
Andere namen:
|
Experimenteel: Stage 2: Cobimetinib Expansion (21/7 Schedule)
Participants will receive cobimetinib at the maximum tolerated dose (MTD) established in Stage 1, once daily for Days 1-21 of each 28-day cycle (21 days on drug followed by 7 days off treatment [21/7 schedule]).
Treatment will continue until progressive disease (PD) or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
|
Repeating oral dose
Andere namen:
|
Experimenteel: Stage 2 A: Cobimetinib Expansion (14/14 Schedule)
Participants will receive cobimetinib at the MTD established in Stage 1A, once daily for Days 1-14 of each 28-day cycle (14 days on drug followed by 14 days off treatment [14/14 schedule]).
Treatment will continue until progressive disease (PD) or unacceptable toxicity for up to 1 year at the discretion of investigator and beyond 1 year with the agreement of the sponsor.
|
Repeating oral dose
Andere namen:
|
Experimenteel: Stage 3: Cobimetinib+Midazolam+Dextromethorphan
Participants will receive a single dose of midazolam (2 mg of midazolam syrup) and dextromethorphan (30 mg tablet) on Cycle 1 Day 1, in the absence of cobimetinib.
After a 2-day washout period, participants will receive 21 consecutive daily doses of cobimetinib (60-mg) followed by a 7-day washout period.
Participants will receive another single dose of midazolam and dextromethorphan on Cycle 1 Day 15, in the presence of steady-state cobimetinib concentrations.
In Cycle 2 and beyond participants will receive cobimetinib alone, administered as a 60-mg daily dose for 21 consecutive days in 28-day cycles (21/7 schedule).
|
Repeating oral dose
Andere namen:
In Stage III only: single dose of dextromethorphan
In Stage III only: single dose of midazolam
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
---|---|---|
Stage 1 and 1A: Number of Participants With Dose Limiting Toxicities (DLTs)
Tijdsspanne: Stage 1 and 1A: Days 1 to 28 of Cycle 1
|
Adverse events (AE) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v3.0. DLT was defined as either of the following occurring during the Study Treatment Period. The occurrence of a drug-related AE that, in the opinion of the cohort review committee (CRC), was of potential clinical significance such that further dose escalation would expose participants in higher dose cohorts to risk of irreversible medical harm or require medical treatment to avoid irreversible medical harm or non-hematologic toxicity
|
Stage 1 and 1A: Days 1 to 28 of Cycle 1
|
Stage 1: Maximum Tolerated Dose (MTD) of Cobimetinib in 21/7 Schedule
Tijdsspanne: Stage 1: Days 1 to 28 of Cycle 1
|
AEs were graded according to the NCI-CTCAE v3.0. A DLT was determined from clinical findings during the Study Treatment Period (Cycle 1, Days 1). MTD was defined as the dose at which no DLTs were observed. DLT was defined as either of the following occurring during the Study Treatment Period. The occurrence of a drug-related AE that, in the opinion of the CRC, was of potential clinical significance such that further dose escalation would expose participants in higher dose cohorts to risk of irreversible medical harm or require medical treatment to avoid irreversible medical harm or non-hematologic toxicity
|
Stage 1: Days 1 to 28 of Cycle 1
|
Stage 1A: MTD of Cobimetinib in 14/14 Schedule
Tijdsspanne: Stage 1A: Days 1 to 28 of Cycle 1
|
AEs were graded according to NCI-CTCAE v3.0. A DLT was the basis for determining MTD in Stage 1A participants. The participants of Stage 1A are dose-escalation cohorts, starting at the MTD of the 21/7 schedule, were treated on a 14/14 schedule to determine the MTD. A DLT was defined as either of the following occurring during the Study Treatment Period: Occurrence of a drug-related AE that, in the opinion of the CRC, was of potential clinical significance such that further dose escalation would expose participants to risk of irreversible medical harm; Nonhematologic toxicity: Grade 3 or 4 events, including Grade 3 nausea and/or vomiting and/or Grade 3 diarrhea, despite prophylaxis and/or treatment; Hematologic toxicity: Grade 4 thrombocytopenia. Grade 4 neutropenia of more than 4 days' duration; Grade 4 neutropenia of any duration with fever or documented infection. AEs (Grade 3 or higher) for which a clinical cause unrelated to cobimetinib was evident was not considered DLTs. |
Stage 1A: Days 1 to 28 of Cycle 1
|
Stage 1: Maximum Observed Concentration (Cmax) of Cobimetinib at Day 1, Cycle 1
Tijdsspanne: Stage 1: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 1 and pre-dose on Cycle 1 Day 2
|
Cmax is defined as the maximum plasma concentration achieved after administration of cobimetinib on Day 1, Cycle 1 in Stage 1 and was measured as nanograms per milliliter (ng/mL).
|
Stage 1: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 1 and pre-dose on Cycle 1 Day 2
|
Stage 1: Area Under the Plasma Cobimetinib Concentration Curve From Time 0 to 24 Hours (AUC 0-24) Day 1, Cycle 1
Tijdsspanne: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2
|
The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration of cobimetinib up to 24 h after administration by the trapezoidal formula.
AUC 0-24 is the truncated AUC over a 24-hour sampling interval.
The concentration-time curve is the result of time points of blood sampling and its measured concentration of free cobimetinib in the blood samples.
AUC is measured as hours times nanograms per milliliter (h*ng/mL).
|
Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2
|
Stage 1: Time to Maximum Concentration (Tmax) of Cobimetinib at Day 1, Cycle 1
Tijdsspanne: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 1 and pre-dose on Cycle 1 Day 2
|
Tmax is defined as the time to reach Cmax during stage 1 at Day 1 Cycle 1.
|
Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 1 and pre-dose on Cycle 1 Day 2
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
---|---|---|
Stage 1: Tmax of Cobimetinib at Steady State
Tijdsspanne: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)
|
Tmax is defined as the time to reach Cmax during stage 1 in steady state.
Steady state was reached when overall intake of cobimetinib was in dynamic equilibrium with its elimination.
|
Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)
|
Stage 1: AUC 0-24 of Cobimetinib at Steady State
Tijdsspanne: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)
|
The area under the AUC0-24 for steady state in stage 1 was calculated with the measured data points from the time of administration of cobimetinib up to 24 h after administration by the trapezoidal formula.
AUC 0-24 is the truncated AUC over a 24-hour sampling interval.
The concentration-time curve is the result of time points of blood sampling and its measured concentration of free cobimetinib in the blood samplings.
|
Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)
|
Stage 1: AUC 0-24/D of Cobimetinib at Steady State
Tijdsspanne: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)
|
AUC 0-24/D is the dose normalized truncated AUC over a 24-hour sampling interval.
|
Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)
|
Stage 1: Accumulation Ratio of Cobimetinib at Steady State
Tijdsspanne: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 1, Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)
|
Accumulation Ratio: AUC0-24 at steady state divided by AUC0-24 on Cycle 1 Day 1.
It was calculated only for participants who had a quantifiable AUC 0-24 at steady state.
|
Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 1, Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)
|
Stage 1: Apparent Clearance of Cobimetinib at Steady State
Tijdsspanne: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)
|
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Apparent clearance was calculated only for participants who had a quantifiable AUC 0-24 in steady state.
|
Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)
|
Stage 1: Half-Life (t1/2) of Cobimetinib at Steady State
Tijdsspanne: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)
|
t1/2 is the half-life of cobimetinib measured over the terminal phase by noncompartmental analysis in stage 1 in steady state.
|
Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)
|
Stage 1: Cmax of Cobimetinib at Steady State
Tijdsspanne: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)
|
Cmax is defined as the maximum plasma concentration achieved after administration of cobimetinib in Stage 1 and was measured at steady state in ng/mL.
|
Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)
|
Stage 1A: Tmax of Cobimetinib at Cycle 1 Day 1
Tijdsspanne: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2
|
Tmax is defined as the time to reach Cmax during stage 1A at Day 1.
|
Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2
|
Stage 1A: Cmax of Cobimetinib at Cycle 1 Day 1
Tijdsspanne: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2
|
Cmax is defined as the maximum plasma concentration achieved after administration of cobimetinib on on Day 1 in Stage 1A and was measured as ng/mL.
|
Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2
|
Stage 1A: AUC 0-24 of Cobimetinib at Cycle 1 Day 1
Tijdsspanne: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2
|
AUC0-24 for stage 1A was calculated on Day 1 with the measured data points from the time of administration of cobimetinib up to 24 h after administration by the trapezoidal formula.
AUC 0-24 is the truncated AUC over a 24-hour sampling interval.
The concentration-time curve is the result of time points of blood sampling and its measured concentration of free cobimetinib in the blood samplings.
|
Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2
|
Stage 1A: t1/2 of Cobimetinib at Steady State
Tijdsspanne: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)
|
t1/2 is the half-life of cobimetinib measured over the terminal phase by noncompartmental analysis in stage 1A in steady state.
|
Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)
|
Stage 1A: Tmax of Cobimetinib at Steady State
Tijdsspanne: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)
|
Tmax is defined as the time to reach Cmax during stage 1A in steady state.
|
Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)
|
Stage 1A: Apparent Clearance of Cobimetinib at Steady State
Tijdsspanne: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)
|
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Apparent clearance was calculated only for participants who had a quantifiable AUC 0-24 in steady state.
|
Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)
|
Stage 1A: Accumulation Ratio of Cobimetinib at Steady State
Tijdsspanne: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)
|
Accumulation Ratio: AUC0-24 at steady state divided by AUC0-24 on Cycle 1 Day 1.
It was calculated only for participants who had a quantifiable AUC 0-24 at steady state.
|
Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)
|
Stage 1A: AUC 0-24 of Cobimetinib at Steady State
Tijdsspanne: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)
|
The area under the AUC0-24 for steady state in stage 1A was calculated with the measured data points from the time of administration of cobimetinib up to 24 h after administration by the trapezoidal formula.
AUC 0-24 is the truncated AUC over a 24-hour sampling interval.
The concentration-time curve is the result of time points of blood sampling and its measured concentration of free cobimetinib in the blood samplings.
|
Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)
|
Stage 1A: AUC 0-24/D of Cobimetinib at Steady State
Tijdsspanne: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)
|
AUC 0-24/D is the dose normalized truncated AUC over a 24-hour sampling interval.
|
Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)
|
Stage 1A: Cmax of Cobimetinib at Steady State
Tijdsspanne: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)
|
Cmax is defined as the maximum plasma concentration achieved after administration of cobimetinib in Stage 1A and was measured in steady state as ng/mL.
|
Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)
|
Stage 2: Cmax of Cobimetinib at Cycle 1 Day 1
Tijdsspanne: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2
|
Cmax is defined as the maximum plasma concentration achieved after administration of cobimetinib in Stage 2 and was measured in ng/mL.
|
Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2
|
Stage 2:AUC 0-24 of Cobimetinib at Cycle 1 Day 1
Tijdsspanne: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2
|
The area under the AUC0-24 on Day 1 in stage 2 was calculated with the measured data points from the time of administration of cobimetinib up to 24 h after administration by the trapezoidal formula.
AUC 0-24 is the truncated AUC over a 24-hour sampling interval.
The concentration-time curve is the result of time points of blood sampling and its measured concentration of free cobimetinib in the blood samplings.
|
Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2
|
Stage 2: Tmax of Cobimetinib at Cycle 1 Day 1
Tijdsspanne: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2
|
Tmax is defined as the time to reach Cmax during stage 2 on Day 1.
|
Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2
|
Stage 2: Tmax of Cobimetinib at Steady State
Tijdsspanne: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28
|
Tmax is defined as the time to reach Cmax during stage 2 in steady state.
|
Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28
|
Stage 2: AUC 0-24 of Cobimetinib at Steady State
Tijdsspanne: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28
|
The area under the AUC0-24 for steady state in stage 2 was calculated with the measured data points from the time of administration of cobimetinib up to 24 h after administration by the trapezoidal formula.
AUC 0-24 is the truncated AUC over a 24-hour sampling interval.
The concentration-time curve is the result of time points of blood sampling and its measured concentration of free cobimetinib in the blood samplings.
|
Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28
|
Stage 2: AUC 0-24/D of Cobimetinib at Steady State
Tijdsspanne: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28
|
AUC 0-24/D is the dose normalized truncated AUC over a 24-hour sampling interval.
|
Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28
|
Stage 2: Accumulation Ratio of Cobimetinib at Steady State
Tijdsspanne: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28
|
Accumulation ratio is AUC0-24 at steady state divided by AUC0-24 on Cycle 1 Day 1.
It was calculated only for participants who had a quantifiable AUC 0-24 at steady state.
|
Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28
|
Stage 2: Apparent Clearance of Cobimetinib at Steady State
Tijdsspanne: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28
|
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Apparent clearance was calculated only for participants who had a quantifiable AUC 0-24 in steady state.
|
Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28
|
Stage 2:Half-Life of Cobimetinib at Steady State
Tijdsspanne: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28
|
T1/2 half-life of cobimetinib measured over the terminal phase by noncompartmental analysis.
|
Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28
|
Stage 2A: AUC 0-24/D of Cobimetinib at Steady State
Tijdsspanne: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28
|
AUC 0-24/D is the dose normalized truncated AUC over a 24-hour sampling interval.
|
Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28
|
Stage 2A: Accumulation Ratio of Cobimetinib at Steady State
Tijdsspanne: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28
|
Accumulation Ratio AUC0-24 is ratio of AUC on Day 20: Day 1.
|
Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28
|
Stage 2A: Apparent Clearance of Cobimetinib at Steady State
Tijdsspanne: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28
|
Apparent clearance is the plasma clearance of absorbed drug.
|
Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28
|
Stage 2A: Half-Life of Cobimetinib at Steady State
Tijdsspanne: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28
|
Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28
|
|
Stage 2A: Tmax of Cobimetinib at Steady State
Tijdsspanne: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28
|
Tmax is defined as the time to reach Cmax during stage 2A in steady state.
|
Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28
|
Stage 2A: Cmax of Cobimetinib at Steady State
Tijdsspanne: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28
|
Cmax is the maximum plasma concentration achieved following the Day 20 dose in Stage 2A.
|
Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28
|
Stage III: Cmax of Dextromethorphan
Tijdsspanne: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1
|
Cmax is defined as maximum observed plasma concentration and was determined both in the presence (Cycle 1 Day 15) and absence of cobimetinib (Cycle 1 Day 1).
|
Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1
|
Stage III: AUC 0-24 of Dextromethorphan
Tijdsspanne: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1
|
AUC0-24 is the area under the plasma drug concentration curve over a 24-hour sampling interval and was determined both in presence (Cycle 1 Day 15) and absence (Cycle 1 Day 1) of cobimetinib.
|
Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1
|
Stage III: AUC 0-inf of Dextromethorphan
Tijdsspanne: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1
|
AUC0-inf is AUC from time 0 to infinity and was calculated both in presence Cycle 1 Day 15) and absence (Cycle 1 Day 1) of cobimetinib.
|
Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1
|
Stage III: Cmax of Midazolam
Tijdsspanne: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1
|
Cmax is the maximum observed plasma concentration and was calculated both in the presence (Cycle 1 Day 15) and absence (Cycle 1 Day 1) of cobimetinib.
|
Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1
|
Stage III: AUC0-24 of Midazolam
Tijdsspanne: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1
|
AUC0-24 is the area under the plasma drug concentration curve over a 24-hour sampling interval and was calculated both in the presence (Cycle 1 Day 15) and absence (CXycle 1 Day 1) of cobimetinib.
|
Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1
|
Stage III: AUC0-inf of Midazolam
Tijdsspanne: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1
|
AUC0-inf is the AUC from time 0 to infinity and was calculated both in the presence (Cycle 1 Day 15) and absence (Cycle 1 Day 1) of cobimetinib.
|
Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1
|
Medewerkers en onderzoekers
Sponsor
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Neoplasmata
- Fysiologische effecten van medicijnen
- Neurotransmitter agenten
- Moleculaire mechanismen van farmacologische werking
- Depressiva van het centrale zenuwstelsel
- Anesthesie, intraveneus
- Anesthesie, generaal
- Anesthesie
- Excitatoire aminozuurantagonisten
- Opwindende aminozuurmiddelen
- Rustgevende agenten
- Psychotrope medicijnen
- Hypnotica en sedativa
- Adjuvantia, anesthesie
- Middelen tegen angst
- GABA-modulatoren
- GABA-agenten
- Agenten van het ademhalingssysteem
- Antitussiva
- Midazolam
- Dextromethorfan
Andere studie-ID-nummers
- MEK4592g
- GO01329 (Andere identificatie: Hoffmann-La Roche)
- XL518-001 (Andere identificatie: Exelixis)
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
product vervaardigd in en geëxporteerd uit de V.S.
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .
Klinische onderzoeken op Vaste tumor
-
Sorrento Therapeutics, Inc.IngetrokkenVaste tumor | Recidiverende vaste tumor | Refractaire tumor
-
Aadi Bioscience, Inc.WervingGeavanceerde vaste tumor | Tumor | Tumor, solideVerenigde Staten
-
Memorial Sloan Kettering Cancer CenterWervingVaste tumor | Vaste tumor, volwassen | Vaste tumor, niet gespecificeerd, volwassenVerenigde Staten
-
Memorial Sloan Kettering Cancer CenterLincoln Medical and Mental Health CenterWervingVaste tumor | Vaste tumor, volwassen | Vaste tumor, niet gespecificeerd, volwassenVerenigde Staten, Puerto Rico
-
Memorial Sloan Kettering Cancer CenterLincoln Medical and Mental Health CenterWervingVaste tumor | Vaste tumor, volwassen | Vaste tumor, niet gespecificeerd, volwassenVerenigde Staten, Puerto Rico
-
RemeGen Co., Ltd.VoltooidMetastatische vaste tumor | Lokaal geavanceerde vaste tumor | Inoperabele vaste tumorAustralië
-
National Health Research Institutes, TaiwanNational Cheng-Kung University HospitalWerving
-
Elpiscience Biopharma, Ltd.Shanghai Junshi Bioscience Co., Ltd.WervingNeoplasmata | Vaste tumor | Kwaadaardige tumorChina
-
The First Affiliated Hospital of Xiamen UniversityWervingVaste tumor | Tumor | Positron-emissietomografieChina
-
Dicerna Pharmaceuticals, Inc., a Novo Nordisk companyWervingVaste tumor, volwassen | Refractaire tumorVerenigde Staten
Klinische onderzoeken op cobimetinib
-
University of UtahGenentech, Inc.WervingChronische myelomonocytische leukemie (CMML)Verenigde Staten
-
University of ArkansasGenentech, Inc.WervingArterioveneuze misvormingen (extracraniaal)Verenigde Staten
-
ImmVira Pharma Co. LtdGeschorstMelanoma | Kwaadaardig melanoomVerenigde Staten
-
Memorial Sloan Kettering Cancer CenterGenentech, Inc.VoltooidHistiocytische aandoeningenVerenigde Staten
-
Genentech, Inc.Voltooid
-
Genentech, Inc.VoltooidNeoplasmataVerenigde Staten, Spanje
-
Carl AllenBaylor College of Medicine; Genentech, Inc.; North American Consortium for HistiocytosisWervingHistiocytisch sarcoom | Juveniel xanthogranuloom | Histiocytaire stoornissen, kwaadaardig | Erdheim-Chester-ziekte | Celhistiocytose van Langerhan | Rosai Dorfman-ziekte | Neuro-degeneratieve ziekteVerenigde Staten
-
Hoffmann-La RocheVoltooidVaste tumorenVerenigde Staten, Spanje, Duitsland, Frankrijk, Israël, Italië, Verenigd Koninkrijk
-
Genentech, Inc.Voltooid
-
ABM Therapeutics CorporationActief, niet wervendGeavanceerde vaste tumor | BRAF V600-mutatieVerenigde Staten