A Study of the Effect of Food on the Pharmacokinetics of Single Dose RO5185426 And the Safety And Efficacy of Continuous Administration in Patients With BRAF V600E Mutation-Positive Metastatic Melanoma
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01264380
Collaborator
(none)
16
10
3
28
1.6
0.1
Study Details
Study Description
Brief Summary
This randomized, open-label, two period crossover study will evaluate the effect of food on the pharmacokinetics of a single dose of RO5185426 and the efficacy and safety of continuous administration in patients with BRAF V600E mutation-positive metastatic melanoma. Patients will be randomized to receive in a crossover design single oral doses of RO5185426 with or without food, with a 10-day washout period between doses. Following the crossover periods, patients will receive RO5185426 orally twice daily on a continuous basis until disease progression or unacceptable toxicity occurs.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
16 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I, Randomized, Open-label, Multi-center, Two Period Crossover Study to Investigate the Effect of Food on the Pharmacokinetics of a Single Oral Dose of RO5185426, Followed by Administration of 960 mg RO5185426 Twice Daily to BRAF V600E Positive Metastatic Melanoma Patients
Study Start Date
:
Jan 1, 2011
Actual Primary Completion Date
:
May 1, 2013
Actual Study Completion Date
:
May 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1
|
Drug: RO5185426
Single oral dose, fasted
|
| Experimental: 2
|
Drug: RO5185426
Single oral dose, with high fat meal
|
| Experimental: C
|
Drug: RO5185426
Continuous administration, orally twice daily
|
Outcome Measures
Primary Outcome Measures
- Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC [0-inf]) in the Fasted and Fed States [Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 hours (h) post-dose (pd) on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd]
Pharmacokinetic (PK) analyses was performed after the completion of Period A and Period B of this study for all participants.
- Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Sample With Last Measurable Concentration (AUC[0-last]) in the Fasted and Fed States [Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd]
PK analyses was performed after the completion of Period A and Period B of this study for all participants.
- Maximal Observed Plasma Concentration (Cmax) in the Fasted and Fed States [Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd]
PK analyses was performed after the completion of Period A and Period B of this study for all participants.
- Minimum Observed (Trough) Plasma Concentration (Cmin) in the Fasted and Fed States [Pre-dose on Periods A and B]
Single dose Pre-dose concentration is referred as Cmin here. PK analyses was performed after the completion of Period A and Period B of this study for all participants.
- Time to Reach Maximal Plasma Concentration (Tmax) in the Fasted and Fed States [Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd]
PK analyses was performed after the completion of Period A and Period B of this study for all participants.
- Terminal Elimination Half-Life (t1/2) in the Fasted and Fed States [Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd]
T1/2 is the time required for the concentration of the drug to reach half of its original value. PK analyses was performed after the completion of Period A and Period B of this study for all participants.
- Apparent First-order Terminal Elimination Rate Constant (Kel) in the Fasted and Fed States [Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd]
Apparent first-order terminal elimination rate constant (kel), was calculated as the negative slope of the linear regression of the terminal phase in plasma vemurafenib concentration-time profile using specific appropriate time points. PK analyses was performed after the completion of Period A and Period B of this study for all participants.
Secondary Outcome Measures
- Percentage of Participants With Best Objective Response (BOR) as Complete Response (CR) or Partial Response (PR) [From Baseline then Day 1 of Cycle 3 and 5 (21-day cycle) at Period C thereafter every 2 cycles until Cycle 12 followed by every 4 cycles from Cycle 13 until disease progression or death (Up to Week 124)]
BOR was defined as the best objective response assessed by investigator during the treatment period according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. BOR was the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation. It is defined as the number of participants whose best objective response was complete response (CR) or partial response (PR) divided by the total number of efficacy evaluable participants. CR: disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) were non-pathological in size (less than [<] 10 millimeter [mm] short axis). PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
- Overall Survival (OS) [From Baseline then Day 1 of Cycle 3 and 5 (21-day cycle) at Period C thereafter every 2 cycles until Cycle 12 followed by every 4 cycles from Cycle 13 until death (Up to Week 124)]
OS was defined as the time, in months, from the date of the first study drug to the date of death, regardless of the cause of death.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Adult patients, >/= 18 years of age
-
Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer)
-
Positive BRAF V600E mutation result determined by Cobas 4800 BRAF V600 Mutation Test
-
Previously treated patients must have failed at least one prior treatment regimen; if patients have received prior systemic treatments for metastatic melanoma, the time elapsed from previous therapy must be >/= 28 days; patients must have recovered fully from toxicities of all prior therapy
-
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
-
Evaluable disease (measurable for disease progression according to RECIST criteria)
-
Adequate hematological, renal and liver function
Exclusion Criteria:
-
Active CNS lesions
-
History of or known spinal cord compression or carcinomatous meningitis
-
Anticipated or ongoing administration of anti-cancer therapies other than those administered in this 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
-
Previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor
-
Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of any type of gastrointestinal surgery that would preclude adequate absorption of study drug
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | La Jolla | California | United States | 92037 | |
| 2 | Los Angeles | California | United States | 90095-1752 | |
| 3 | San Francisco | California | United States | 94115-1705 | |
| 4 | Aurora | Colorado | United States | 80045 | |
| 5 | Indianapolis | Indiana | United States | 46202 | |
| 6 | Iowa City | Iowa | United States | 52242 | |
| 7 | Lebanon | New Hampshire | United States | 03756 | |
| 8 | Charleston | South Carolina | United States | 29425 | |
| 9 | Nashville | Tennessee | United States | 37232 | |
| 10 | Dallas | Texas | United States | 75246 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01264380
Other Study ID Numbers:
- NP25396
First Posted:
Dec 21, 2010
Last Update Posted:
Nov 2, 2016
Last Verified:
Nov 1, 2016
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Vemurafenib (RO5185426): Fasted Then Fed | Vemurafenib (RO5185426): Fed Then Fasted | Vemurafenib (RO5185426) |
|---|---|---|---|
| Arm/Group Description | Single oral dose of vemurafenib tablet at 960 milligrams (mg) on Day 1 was administered to participants in fasted condition (Period A [Day 1 to Day 10]) followed by single oral dose of vemurafenib tablet at 960 mg on Day 1 in fed condition (Period B [Day 11 to Day 20]). A washout period of 10 days was maintained between Period A and B. | Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition (Period A [Day 1 to Day 10]) followed by single oral dose of vemurafenib tablet at 960 mg on Day 1 in fasted condition Period B [Day 11 to Day 20]). A washout period of 10 days was maintained between Period A and B. | Participants received vemurafenib tablet at 960 mg orally twice daily in 21-day cycles starting from Day 21 until disease progression, unacceptable toxicity, or consent withdrawal (Period C). |
| Period Title: Period A | |||
| STARTED | 8 | 8 | 0 |
| COMPLETED | 8 | 8 | 0 |
| NOT COMPLETED | 0 | 0 | 0 |
| Period Title: Period A | |||
| STARTED | 8 | 8 | 0 |
| COMPLETED | 8 | 8 | 0 |
| NOT COMPLETED | 0 | 0 | 0 |
| Period Title: Period A | |||
| STARTED | 0 | 0 | 16 |
| COMPLETED | 0 | 0 | 2 |
| NOT COMPLETED | 0 | 0 | 14 |
Baseline Characteristics
| Arm/Group Title | All Participants |
|---|---|
| Arm/Group Description | Included all participants who received single oral dose of vemurafenib tablet at 960 mg in fasted condition first and fed condition first in Period A and Period B and twice daily dose of vemurafenib tablet at 960 mg in Period C. |
| Overall Participants | 16 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
60.6
(10.31)
|
| Gender (Count of Participants) | |
| Female |
6
37.5%
|
| Male |
10
62.5%
|
Outcome Measures
| Title | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC [0-inf]) in the Fasted and Fed States |
|---|---|
| Description | Pharmacokinetic (PK) analyses was performed after the completion of Period A and Period B of this study for all participants. |
| Time Frame | Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 hours (h) post-dose (pd) on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis population included participants who received both single doses of vemurafenib in Periods A and B without protocol violation and provided adequate PK assessments to calculate important PK parameters. Here "number of participants analyzed"=participants who were evaluable for this outcome measure. |
| Arm/Group Title | Vemurafenib (RO5185426): Fasted | Vemurafenib (RO5185426): Fed |
|---|---|---|
| Arm/Group Description | Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B). | Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B). |
| Measure Participants | 16 | 15 |
| Mean (Standard Deviation) [micrograms*hour per milliliter (µg*h/mL)] |
115
(110)
|
351
(189)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Vemurafenib (RO5185426): Fasted, Vemurafenib (RO5185426): Fed |
|---|---|---|
| Comments | The point estimate and 90 percent (%) confidence interval (CI) of vemurafenib plasma AUC geometric means ratios of the Fed to Fasted conditions following an oral administration of a single dose of 960 mg vemurafenib were analyzed. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric Mean |
| Estimated Value | 4.64 | |
| Confidence Interval |
(2-Sided) 90% 2.83 to 7.60 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Sample With Last Measurable Concentration (AUC[0-last]) in the Fasted and Fed States |
|---|---|
| Description | PK analyses was performed after the completion of Period A and Period B of this study for all participants. |
| Time Frame | Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis population. Here "number of participants analyzed"=participants who were evaluable for this outcome measure. |
| Arm/Group Title | Vemurafenib (RO5185426): Fasted | Vemurafenib (RO5185426): Fed |
|---|---|---|
| Arm/Group Description | Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B). | Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B). |
| Measure Participants | 15 | 14 |
| Mean (Standard Deviation) [µg*h/mL] |
94.3
(81.8)
|
320
(158)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Vemurafenib (RO5185426): Fasted, Vemurafenib (RO5185426): Fed |
|---|---|---|
| Comments | The point estimate and 90% CI of vemurafenib plasma AUC geometric means ratios of the Fed to Fasted conditions following an oral administration of a single dose of 960 mg vemurafenib were analyzed. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric Mean |
| Estimated Value | 5.05 | |
| Confidence Interval |
(2-Sided) 90% 2.99 to 8.55 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maximal Observed Plasma Concentration (Cmax) in the Fasted and Fed States |
|---|---|
| Description | PK analyses was performed after the completion of Period A and Period B of this study for all participants. |
| Time Frame | Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis population. |
| Arm/Group Title | Vemurafenib (RO5185426): Fasted | Vemurafenib (RO5185426): Fed |
|---|---|---|
| Arm/Group Description | Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B). | Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B). |
| Measure Participants | 16 | 16 |
| Mean (Standard Deviation) [µg/mL] |
3.48
(2.02)
|
7.38
(1.98)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Vemurafenib (RO5185426): Fasted, Vemurafenib (RO5185426): Fed |
|---|---|---|
| Comments | The point estimate and 90% CI of vemurafenib plasma Cmax geometric means ratios of the Fed to Fasted conditions following an oral administration of a single dose of 960 mg vemurafenib were analyzed. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric Mean |
| Estimated Value | 2.45 | |
| Confidence Interval |
(2-Sided) 90% 1.81 to 3.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Minimum Observed (Trough) Plasma Concentration (Cmin) in the Fasted and Fed States |
|---|---|
| Description | Single dose Pre-dose concentration is referred as Cmin here. PK analyses was performed after the completion of Period A and Period B of this study for all participants. |
| Time Frame | Pre-dose on Periods A and B |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis population. |
| Arm/Group Title | Vemurafenib (RO5185426): Fasted | Vemurafenib (RO5185426): Fed |
|---|---|---|
| Arm/Group Description | Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B). | Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B). |
| Measure Participants | 16 | 16 |
| Mean (Standard Deviation) [µg/mL] |
NA
(NA)
|
NA
(NA)
|
| Title | Time to Reach Maximal Plasma Concentration (Tmax) in the Fasted and Fed States |
|---|---|
| Description | PK analyses was performed after the completion of Period A and Period B of this study for all participants. |
| Time Frame | Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis population. |
| Arm/Group Title | Vemurafenib (RO5185426): Fasted | Vemurafenib (RO5185426): Fed |
|---|---|---|
| Arm/Group Description | Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B). | Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B). |
| Measure Participants | 16 | 16 |
| Median (Full Range) [hour] |
4
|
7.51
|
| Title | Terminal Elimination Half-Life (t1/2) in the Fasted and Fed States |
|---|---|
| Description | T1/2 is the time required for the concentration of the drug to reach half of its original value. PK analyses was performed after the completion of Period A and Period B of this study for all participants. |
| Time Frame | Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis population. Here "number of participants analyzed"=participants who were evaluable for this outcome measure. |
| Arm/Group Title | Vemurafenib (RO5185426): Fasted | Vemurafenib (RO5185426): Fed |
|---|---|---|
| Arm/Group Description | Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B). | Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B). |
| Measure Participants | 16 | 15 |
| Mean (Standard Deviation) [hour] |
24.6
(17.2)
|
26.0
(17.1)
|
| Title | Apparent First-order Terminal Elimination Rate Constant (Kel) in the Fasted and Fed States |
|---|---|
| Description | Apparent first-order terminal elimination rate constant (kel), was calculated as the negative slope of the linear regression of the terminal phase in plasma vemurafenib concentration-time profile using specific appropriate time points. PK analyses was performed after the completion of Period A and Period B of this study for all participants. |
| Time Frame | Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis population. Here "number of participants analyzed"=participants who were evaluable for this outcome measure. |
| Arm/Group Title | Vemurafenib (RO5185426): Fasted | Vemurafenib (RO5185426): Fed |
|---|---|---|
| Arm/Group Description | Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B). | Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B). |
| Measure Participants | 15 | 14 |
| Mean (Standard Deviation) [1/h] |
0.04
(0.03)
|
0.04
(0.02)
|
| Title | Percentage of Participants With Best Objective Response (BOR) as Complete Response (CR) or Partial Response (PR) |
|---|---|
| Description | BOR was defined as the best objective response assessed by investigator during the treatment period according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. BOR was the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation. It is defined as the number of participants whose best objective response was complete response (CR) or partial response (PR) divided by the total number of efficacy evaluable participants. CR: disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) were non-pathological in size (less than [<] 10 millimeter [mm] short axis). PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Time Frame | From Baseline then Day 1 of Cycle 3 and 5 (21-day cycle) at Period C thereafter every 2 cycles until Cycle 12 followed by every 4 cycles from Cycle 13 until disease progression or death (Up to Week 124) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included participants with measurable disease who received at least 1 dose of vemurafenib. Here "number of participants analyzed"=participants who were evaluable for this outcome measure. |
| Arm/Group Title | Vemurafenib (RO5185426) |
|---|---|
| Arm/Group Description | Participants received vemurafenib tablet at 960 mg orally twice daily in 21-day cycles starting from Day 21 until disease progression, unacceptable toxicity, or consent withdrawal (Period C). |
| Measure Participants | 14 |
| Number (95% Confidence Interval) [percentage of participants] |
64.3
401.9%
|
| Title | Overall Survival (OS) |
|---|---|
| Description | OS was defined as the time, in months, from the date of the first study drug to the date of death, regardless of the cause of death. |
| Time Frame | From Baseline then Day 1 of Cycle 3 and 5 (21-day cycle) at Period C thereafter every 2 cycles until Cycle 12 followed by every 4 cycles from Cycle 13 until death (Up to Week 124) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data for OS was not collected as there was a change in planned analysis, not to collect the data. |
| Arm/Group Title | Vemurafenib (RO5185426) |
|---|---|
| Arm/Group Description | Participants received vemurafenib tablet at 960 mg orally twice daily in 21-day cycles starting from Day 21 until disease progression, unacceptable toxicity, or consent withdrawal (Period C). |
| Measure Participants | 0 |
Adverse Events
| Time Frame | Baseline up to 28 days after last dose (Week 114) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Vemurafenib (RO5185426): Fasted | Vemurafenib (RO5185426): Fed | Vemurafenib (RO5185426) | |||
| Arm/Group Description | Single oral dose of vemurafenib tablet at 960 milligram (mg) on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B). | Single oral dose of vemurafenib tablet at 960 milligram (mg) on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B). | Participants received vemurafenib tablet at 960 mg orally twice daily in 21-day cycles starting from Day 21 until disease progression, unacceptable toxicity, or consent withdrawal (Period C). | |||
All Cause Mortality |
||||||
| Vemurafenib (RO5185426): Fasted | Vemurafenib (RO5185426): Fed | Vemurafenib (RO5185426) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Vemurafenib (RO5185426): Fasted | Vemurafenib (RO5185426): Fed | Vemurafenib (RO5185426) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/16 (0%) | 0/16 (0%) | 9/16 (56.3%) | |||
| Cardiac disorders | ||||||
| Coronary artery disease | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Gastrointestinal disorders | ||||||
| Mesenteric vein thrombosis | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Infections and infestations | ||||||
| Cellulitis | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Investigations | ||||||
| Transaminases increased | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Squamous cell carcinoma of skin | 0/16 (0%) | 0/16 (0%) | 5/16 (31.3%) | |||
| Keratoacanthoma | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Basal cell carcinoma | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Nervous system disorders | ||||||
| Haemorrhage intracranial | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Vemurafenib (RO5185426): Fasted | Vemurafenib (RO5185426): Fed | Vemurafenib (RO5185426) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/16 (18.8%) | 5/16 (31.3%) | 16/16 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Haemorrhagic diathesis | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Cardiac disorders | ||||||
| Sinus bradycardia | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Tachycardia | 0/16 (0%) | 1/16 (6.3%) | 2/16 (12.5%) | |||
| Eye disorders | ||||||
| Blepharitis | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Cataract | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Conjunctival hyperaemia | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Diplopia | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Dry eye | 0/16 (0%) | 0/16 (0%) | 6/16 (37.5%) | |||
| Eye irritation | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Eye pain | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Lacrimation increased | 0/16 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Ocular hyperaemia | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Ocular rosacea | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Photophobia | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Vision blurred | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Vitreous floaters | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal distention | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Cheilitis | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Abdominal pain | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Constipation | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Diarrhoea | 0/16 (0%) | 1/16 (6.3%) | 6/16 (37.5%) | |||
| Dyspepsia | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Gingival pain | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Hiatus hernia | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Lip swelling | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Nausea | 0/16 (0%) | 0/16 (0%) | 5/16 (31.3%) | |||
| Oral disorder | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Stomatitis | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Toothache | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Vomiting | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| General disorders | ||||||
| Chest discomfort | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Chills | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Fatigue | 1/16 (6.3%) | 1/16 (6.3%) | 10/16 (62.5%) | |||
| Influenza like illness | 0/16 (0%) | 0/16 (0%) | 3/16 (18.8%) | |||
| Oedema peripheral | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Pyrexia | 1/16 (6.3%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Hepatobiliary disorders | ||||||
| Cholelithiasis | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Infections and infestations | ||||||
| Bronchitis | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Chronic sinusitis | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Conjunctivitis infective | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Gastroenteritis viral | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Nasopharyngitis | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Onychomycosis | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Oral candidiasis | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Pneumonia pseudomonas aeruginosa | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Sinusitis | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Upper respiratory tract infection | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Urinary tract infection | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Injury, poisoning and procedural complications | ||||||
| Contusion | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Incision site pain | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Investigations | ||||||
| Aspartate aminotransferase increased | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Blood alkaline phosphatase increased | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Blood creatinine increased | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Breath sounds abnormal | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Gamma-glutamyltransferase increased | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Neutrophil count increased | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 0/16 (0%) | 0/16 (0%) | 5/16 (31.3%) | |||
| Dehydration | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Hypercalcaemia | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Hypercholesterolaemia | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Hyperglycaemia | 0/16 (0%) | 0/16 (0%) | 3/16 (18.8%) | |||
| Hyperlipidaemia | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Hypoglycaemia | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Hypokalaemia | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Hypomagnesaemia | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/16 (0%) | 0/16 (0%) | 10/16 (62.5%) | |||
| Back pain | 0/16 (0%) | 0/16 (0%) | 3/16 (18.8%) | |||
| Joint effusion | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Muscular weakness | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Musculoskeletal pain | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Myalgia | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Neck pain | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Pain in extremity | 0/16 (0%) | 0/16 (0%) | 3/16 (18.8%) | |||
| Sensation of heaviness | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Dysplastic naevus | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Haemangioma | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Keratoacanthoma | 0/16 (0%) | 0/16 (0%) | 3/16 (18.8%) | |||
| Lipoma | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Melanocytic naevus | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Metastatic pain | 0/16 (0%) | 1/16 (6.3%) | 0/16 (0%) | |||
| Pyogenic granuloma | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Seborrhoeic keratosis | 0/16 (0%) | 0/16 (0%) | 6/16 (37.5%) | |||
| Skin papilloma | 0/16 (0%) | 0/16 (0%) | 6/16 (37.5%) | |||
| Tumour pain | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Nervous system disorders | ||||||
| Aphasia | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Cerebrovascular accident | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Dizziness | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Dysgeusia | 0/16 (0%) | 0/16 (0%) | 3/16 (18.8%) | |||
| Headache | 1/16 (6.3%) | 0/16 (0%) | 5/16 (31.3%) | |||
| Paraesthesia | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Psychiatric disorders | ||||||
| Agitation | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Anxiety | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Claustrophobia | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Depression | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Insomnia | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Mental status changes | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Renal and urinary disorders | ||||||
| Haematuria | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Proteinuria | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Reproductive system and breast disorders | ||||||
| Gynaecomastia | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Ovarian cyst | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Dyspnoea | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Nasal congestion | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Oropharyngeal pain | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Pleural effusion | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Respiratory disorder | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Rhinitis allergic | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Dyspnoea Paroxysmal Nocturna | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Acne Conglobata | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Actinic keratosis | 0/16 (0%) | 0/16 (0%) | 6/16 (37.5%) | |||
| Alopecia | 0/16 (0%) | 0/16 (0%) | 6/16 (37.5%) | |||
| Dermal cyst | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Dermatitis acneiform | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Dry skin | 0/16 (0%) | 0/16 (0%) | 5/16 (31.3%) | |||
| Eczema | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Erythema | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Erythema nodosum | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Granuloma skin | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Hair texture abnormal | 0/16 (0%) | 0/16 (0%) | 3/16 (18.8%) | |||
| Hyperkeratosis | 0/16 (0%) | 0/16 (0%) | 12/16 (75%) | |||
| Neurodermatitis | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Night sweats | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Palmar-plantar erythrodysaesthesia syndrome | 0/16 (0%) | 0/16 (0%) | 6/16 (37.5%) | |||
| Panniculitis | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Photosensitivity reaction | 0/16 (0%) | 0/16 (0%) | 7/16 (43.8%) | |||
| Pruritus | 1/16 (6.3%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Pruritus generalised | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Purpura | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Rash | 0/16 (0%) | 0/16 (0%) | 4/16 (25%) | |||
| Rash erythematous | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
| Rash maculo-papular | 0/16 (0%) | 0/16 (0%) | 6/16 (37.5%) | |||
| Rash papular | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Skin hypertrophy | 0/16 (0%) | 0/16 (0%) | 3/16 (18.8%) | |||
| Skin lesion | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Skin mass | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) | |||
| Vascular disorders | ||||||
| Hypertension | 0/16 (0%) | 0/16 (0%) | 3/16 (18.8%) | |||
| Hypotension | 1/16 (6.3%) | 1/16 (6.3%) | 1/16 (6.3%) | |||
| Vasculitis | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) | |||
Limitations/Caveats
Results for OS was not reported due to change in planned analysis.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann-La Roche |
| Phone | 800-821-8590 |
| genentech@druginfo.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01264380
Other Study ID Numbers:
- NP25396
First Posted:
Dec 21, 2010
Last Update Posted:
Nov 2, 2016
Last Verified:
Nov 1, 2016