A Study of Vemurafenib in Participants With BRAF V600 Mutation-Positive Cancers
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01524978
Collaborator
(none)
208
34
7
54.5
6.1
0.1
Study Details
Study Description
Brief Summary
This open-label, multi-center study will assess the efficacy and safety of vemurafenib in participants with BRAF V600 mutation-positive cancers (solid tumors and multiple myeloma, except melanoma and papillary thyroid cancer) and for whom vemurafenib is deemed the best treatment option in the opinion of the investigator. Participants will receive twice daily oral doses of 960 mg vemurafenib until disease progression, unacceptable toxicity, or withdrawal of consent. The safety and efficacy of vemurafenib in combination with cetuximab in a subset of participants with colorectal cancer will also be assessed.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
208 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Phase II Study of Vemurafenib in Patients With BRAF V600 Mutation-positive Cancers
Actual Study Start Date
:
Apr 12, 2012
Actual Primary Completion Date
:
Oct 28, 2016
Actual Study Completion Date
:
Oct 28, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - vemurafenib Participants with NSCLC will be treated with vemurafenib monotherapy. |
Drug: vemurafenib
960 mg vemurafenib orally twice a day until disease progression, unacceptable toxicity, or withdrawal of consent.
Other Names:
|
| Experimental: Cohort 2: Ovarian Cancer - vemurafenib Participants with ovarian cancer will be treated with vemurafenib monotherapy. |
Drug: vemurafenib
960 mg vemurafenib orally twice a day until disease progression, unacceptable toxicity, or withdrawal of consent.
Other Names:
|
| Experimental: Cohort 3a: Colorectal Cancer - vemurafenib Participants with colorectal cancer will be treated with vemurafenib monotherapy. |
Drug: vemurafenib
960 mg vemurafenib orally twice a day until disease progression, unacceptable toxicity, or withdrawal of consent.
Other Names:
|
| Experimental: Cohort 3b: Colorectal Cancer - vemurafenib + cetuximab Participants with colorectal cancer will be treated with vemurafenib and cetuximab combination therapy. |
Drug: cetuximab
Escalating doses administered on Day 1 and then once weekly by intravenous infusion.
Drug: vemurafenib
Escalating doses given orally twice a day starting on Day 2
Other Names:
|
| Experimental: Cohort 4: Cholangiocarcinoma - vemurafenib Participants with cholangiocarcinoma will be treated with vemurafenib monotherapy. |
Drug: vemurafenib
960 mg vemurafenib orally twice a day until disease progression, unacceptable toxicity, or withdrawal of consent.
Other Names:
|
| Experimental: Cohort 6: Multiple Myeloma - vemurafenib Participants with multiple myeloma will be treated with vemurafenib monotherapy. |
Drug: vemurafenib
960 mg vemurafenib orally twice a day until disease progression, unacceptable toxicity, or withdrawal of consent.
Other Names:
|
| Experimental: Cohort 7: Other Solid Tumors - vemurafenib Participants with Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LCH), anaplastic thyroid cancer, advanced stage astrocytoma, early stage astrocytoma and other BRAF V600-positive tumors will be treated with vemurafenib monotherapy. Subcohorts will be analyzed separately if 7 or more participants are enrolled for each indication. |
Drug: vemurafenib
960 mg vemurafenib orally twice a day until disease progression, unacceptable toxicity, or withdrawal of consent.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Confirmed Best Overall Response Rate (BORR) [Up to approximately 3 years]
Confirmed BORR: percentage of participants with an objective response (OR) (complete response [CR], partial response [PR], stringent CR [sCR] or very good PR [VGPR]) on 2 occasions >/= 4 weeks apart as assessed by the Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. or International Myeloma Working Group (IMWG) criteria. RECIST v1.1: CR: disappearance of all target lesions; PR: >/= 30% decrease in the sum of diameters of target lesions. IMWG: CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and </= 5% plasma cells in bone marrow; PR: >/= 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >/= 90% or to <200 mg per 24 hours. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or >/= 90% reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hour; sCR: CR plus normal free light chain (FLC) ratio and no clonal cells in bone marrow.
Secondary Outcome Measures
- Percentage of Participants With Confirmed Clinical Benefit [Up to approximately 3 years]
Included were participants with confirmed PR or CR or Stable Disease (SD) that had lasted at least 6 months according to RECIST v1.1 or confirmed CR, PR, VGPR, sCR or SD for at least 6 months according to IMWG criteria. RECIST v1.1: PR: >/= 30% decrease in the sum of diameters of target lesions; CR: disappearance of all target lesions; SD: not meeting criteria for CR, PR or progressive disease (PD). IMWG: CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and </= 5% plasma cells in bone marrow; PR: >/= 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >/= 90% or to <200 mg per 24 hours. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or >/= 90% reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hour; sCR: CR plus normal FLC ratio and no clonal cells in bone marrow; SD: not meeting criteria for CR, VGPR, PR or PD.
- Overall Response Rate (ORR) [Up to approximately 3 years]
ORR: percentage of participants with an objective response (OR) (CR, PR, sCR or VGPR) on 2 occasions >/= 4 weeks apart as assessed by the Investigator using RECIST v1.1. or IMWG criteria. RECIST v1.1: CR: disappearance of all target lesions; PR: >/= 30% decrease in the sum of diameters of target lesions. IMWG: CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and </= 5% plasma cells in bone marrow; PR: >/= 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >/= 90% or to <200 mg per 24 hours. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or >/= 90% reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hour; sCR: CR plus normal FLC ratio and no clonal cells in bone marrow.
- Duration of Response (DOR) [Up to approximately 3 years]
DOR was defined as the period from the date of initial PR or CR for solid tumors according to RECISTv1.1 and CR, PR, VGPR or sCR for multiple myeloma according to IMWG criteria, until the date of PD or death from any cause. RECIST v1.1: PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. IMWG: PD: increase of >/= 25% from lowest response value in serum or urine M-protein or bone marrow plasma cell percentage or development of new or increase in size of bone lesions or soft tissue plasmacytomas.
- Time to Response [Up to approximately 3 years]
Time to response was defined as the time from the first day of study treatment to the date of first CR, or PR for solid tumors according to RECISTv1.1 and CR, PR, VGPR or sCR for multiple myeloma according to IMWG criteria. RECIST v1.1: CR: disappearance of all target lesions; PR: at least a 30% decrease in the sum of diameters of target lesions. IMWG criteria: CR: negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and </= 5% plasma cells in bone marrow; PR: >/= 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >/= 90% or to < 200 mg per 24 hours. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or >/= 90% reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hour; sCR: CR plus normal FLC ratio and no clonal cells in bone marrow.
- Time to Tumor Progression (TTP) [Up to approximately 3 years]
TTP was defined as time from the first day of study treatment to the first occurrence of progressive disease (PD). RECIST v1.1: PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. IMWG: PD: increase of >/= 25% from lowest response value in serum or urine M-protein or bone marrow plasma cell percentage or development of new or increase in size of bone lesions or soft tissue plasmacytomas.
- Progression Free Survival (PFS) [Up to approximately 3 years]
PFS was defined as the time from the first day of study treatment, until the first documented PD or death from any cause, whichever occurs first. RECIST v1.1: PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. IMWG criteria: PD: increase of >/= 25% from lowest response value in serum or urine M-protein or bone marrow plasma cell percentage or development of new or increase in size of bone lesions or soft tissue plasmacytomas.
- Overall Survival (OS) [Up to approximately 3 years]
OS was defined as time between the first day of study treatment and date of death of any cause.
- Maximum Tolerated Dose for Vemurafenib in Combination With Cetuximab [Up to approximately 3 years]
Cohort 3b included participants with colorectal cancer treated with escalating doses of vemurafenib and cetuximab. The escalating doses were as follows: Dose Level 1: 720 milligrams (mg) of vemurafenib orally twice daily starting on Day 2 of Cycle 1 and 300 milligrams per square meter (mg/m^2) loading dose of cetuximab by infusion and then 200 mg/m^2 weekly; Dose Level 2: 720 mg of vemurafenib twice daily starting on Day 2 of Cycle 1 and 400 mg/m^2 loading dose of cetuximab and then 250 mg/m^2 weekly; Dose Level 3: 960 mg of vemurafenib twice daily starting on Day 2 of Cycle 1 and 400 mg/m^2 loading dose of cetuximab and then 250 mg/m^2 weekly. Reported here are the maximum tolerated doses for each vemurafenib and cetuximab.
- Number of Dose-limiting Toxicities of Vemurafenib in Combination With Cetuximab [Up to 28 days]
Cohort 3b included participants with colorectal cancer treated with escalating doses of vemurafenib and cetuximab. The escalating doses were as follows: Dose Level 1: 720 milligrams (mg) of vemurafenib orally twice daily starting on Day 2 of Cycle 1 and 300 milligrams per square meter (mg/m^2) loading dose of cetuximab by infusion and then 200 mg/m^2 weekly; Dose Level 2: 720 mg of vemurafenib twice daily starting on Day 2 of Cycle 1 and 400 mg/m^2 loading dose of cetuximab and then 250 mg/m^2 weekly; Dose Level 3: 960 mg of vemurafenib twice daily starting on Day 2 of Cycle 1 and 400 mg/m^2 loading dose of cetuximab and then 250 mg/m^2 weekly. Reported here are type and number of dose limited toxicities observed.
- Safety: Percentage of Participants With Adverse Event [Up to approximately 3 years]
An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Eligibility Criteria
Criteria
Ages Eligible for Study:
16 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
-
Must have recovered from all side effects of their most recent systemic or local treatment
-
Adequate hematological, renal and liver function
For solid tumors only:
-
Histologically confirmed cancers (excluding melanoma and papillary thyroid cancer) with a BRAF V600 mutation and that are resistant to standard therapy or for which standard or curative therapy does not exist
-
Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST)
For multiple myeloma only:
-
Confirmed diagnosis of multiple myeloma with a BRAF V600 mutation
-
Must have received at least one prior systemic therapy for the treatment of multiple myeloma
-
Treated with local radiotherapy
-
Must have relapsed and/or refractory multiple myeloma with measurable disease
Exclusion Criteria:
-
Melanoma, papillary thyroid cancer or hematological malignancies (with the exception of multiple myeloma)
-
Uncontrolled concurrent malignancy
-
Multiple myeloma: solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia
-
Active or untreated central nervous system (CNS) metastases
-
History of or known carcinomatous meningitis
-
Concurrent administration of any anti-cancer therapies other than those administered in this study
-
Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that would, in the investigator's opinion, contraindicate participation in this study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Arizona Oncology | Tucson | Arizona | United States | 85704 |
| 2 | Rocky Mountain Cancer Centers, LLP | Aurora | Colorado | United States | 80012 |
| 3 | Massachusetts General Hospital;Oncology | Boston | Massachusetts | United States | 02114 |
| 4 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
| 5 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 6 | Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
| 7 | Washington University | Saint Louis | Missouri | United States | 63110 |
| 8 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | |
| 9 | Vanderbilt | Nashville | Tennessee | United States | 37232 |
| 10 | University of Texas M.D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 11 | Yakima Valley Memorial Hospital/North Star Lodge | Yakima | Washington | United States | 98902 |
| 12 | Tianjin Cancer Hospital | Tianjin | China | 300060 | |
| 13 | Institut Bergonie; Oncologie | Bordeaux | France | 33076 | |
| 14 | Centre Francois Baclesse; Oncologie | Caen | France | 14076 | |
| 15 | Centre Georges François Leclerc | Dijon | France | 21000 | |
| 16 | Centre Leon Berard; Departement Oncologie Medicale | Lyon | France | 69373 | |
| 17 | Institut Paoli-Calmettes; Oncologie Medicale 1 | Marseille Cedex 09 | France | 13273 | |
| 18 | Centre Rene Gauducheau | Saint Herblain | France | 44805 | |
| 19 | Institut Claudius Regaud; Departement Oncologie Medicale | Toulouse | France | 31059 | |
| 20 | Institut Gustave Roussy; Sitep | VILLEJUIF Cedex | France | 94805 | |
| 21 | Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung | Essen | Germany | 45122 | |
| 22 | Klinik der Uni zu Koeln; Klinik I für Innere Medizin; Onkologie | Köln | Germany | 50937 | |
| 23 | Universitätsklinikum Mannheim, Tagestherapiezentrum, Interdisziplinäres Tumorzentrum | Mannheim | Germany | 68167 | |
| 24 | Hospital Univ. Central de Asturias; Servicio de Oncologia | Oviedo | Asturias | Spain | 33011 |
| 25 | Hospital del Mar; Servicio de Oncologia | Barcelona | Spain | 08003 | |
| 26 | Hospital Univ Vall d'Hebron; Servicio de Oncologia | Barcelona | Spain | 08035 | |
| 27 | Hospital General Universitario Gregorio Marañon; Servicio de Oncologia | Madrid | Spain | 28007 | |
| 28 | Fundacion Jimenez Diaz; Servicio de Oncologia | Madrid | Spain | 28040 | |
| 29 | Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica | Madrid | Spain | 28050 | |
| 30 | Hospital Clinico Universitario de Salamanca; Servicio de Oncologia | Salamanca | Spain | 37007 | |
| 31 | Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia | Valencia | Spain | 46010 | |
| 32 | Aberdeen Royal Infirmary | Aberdeen | United Kingdom | AB25 2ZN | |
| 33 | The Royal Marsden Hospital; Dept of Medicine | London | United Kingdom | SW3 5PT | |
| 34 | The Royal Marsden Hospital | Sutton | United Kingdom | SM2 5PT |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01524978
Other Study ID Numbers:
- MO28072
- 2011-004426-10
First Posted:
Feb 2, 2012
Last Update Posted:
Nov 20, 2017
Last Verified:
Oct 1, 2017
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | One participant with breast cancer was screened shortly after Cohort 5 (Breast Cancer) had been closed. This participant was allowed to enter the study in Cohort 7: Other BRAF V600-positive tumors. For analysis purposes Cohort 7 was split into sub-cohorts for indications with sufficient participants. |
| Arm/Group Title | Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - Vemurafenib | Cohort 2: Ovarian Cancer - Vemurafenib | Cohort 3a: Colorectal Cancer - Vemurafenib | Cohort 3b: Colorectal Cancer - Vemurafenib + Cetuximab | Cohort 4: Cholangiocarcinoma - Vemurafenib | Cohort 6: Multiple Myeloma - Vemurafenib | Cohort 7a: ECD/LCH - Vemurafenib | Cohort 7b: Anaplastic Thyroid Cancer - Vemurafenib | Cohort 7c: Advanced Stage Astrocytoma - Vemurafenib | Cohort 7d: Early Stage Astrocytoma - Vemurafenib | Cohort 7: Other BRAF V600-positive Tumors - Vemurafenib |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with NSCLC were treated with vemurafenib monotherapy. | Participants with ovarian cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib and cetuximab combination therapy. | Participants with cholangiocarcinoma were treated with vemurafenib monotherapy. | Participants with multiple myeloma were treated with vemurafenib monotherapy. | Participants with Erdheim-Chester disease (ECD) or Langerhans cell histiocytosis (LCH) were treated with vemurafenib monotherapy. | Participants with anaplastic thyroid cancer were treated with vemurafenib monotherapy. | Participants with advanced stage astrocytoma were treated with vemurafenib monotherapy. | Participants with early stage astrocytoma were treated with vemurafenib monotherapy. | Participants with other BRAF V600-positive tumors were treated with vemurafenib monotherapy. |
| Period Title: Overall Study | |||||||||||
| STARTED | 62 | 4 | 10 | 27 | 9 | 9 | 26 | 12 | 12 | 9 | 28 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 62 | 4 | 10 | 27 | 9 | 9 | 26 | 12 | 12 | 9 | 28 |
Baseline Characteristics
| Arm/Group Title | Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - Vemurafenib | Cohort 2: Ovarian Cancer - Vemurafenib | Cohort 3a: Colorectal Cancer - Vemurafenib | Cohort 3b: Colorectal Cancer - Vemurafenib + Cetuximab | Cohort 4: Cholangiocarcinoma - Vemurafenib | Cohort 6: Multiple Myeloma - Vemurafenib | Cohort 7a: ECD/LCH - Vemurafenib | Cohort 7b: Anaplastic Thyroid Cancer - Vemurafenib | Cohort 7c: Advanced Stage Astrocytoma - Vemurafenib | Cohort 7d: Early Stage Astrocytoma - Vemurafenib | Cohort 7: Other BRAF V600-positive Tumors - Vemurafenib | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with NSCLC were treated with vemurafenib monotherapy. | Participants with ovarian cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib and cetuximab combination therapy. | Participants with cholangiocarcinoma were treated with vemurafenib monotherapy. | Participants with multiple myeloma were treated with vemurafenib monotherapy. | Participants with Erdheim-Chester disease (ECD) or Langerhans cell histiocytosis (LCH) were treated with vemurafenib monotherapy. | Participants with anaplastic thyroid cancer were treated with vemurafenib monotherapy. | Participants with advanced stage astrocytoma were treated with vemurafenib monotherapy. | Participants with early stage astrocytoma were treated with vemurafenib monotherapy. | Participants with other BRAF V600-positive tumors were treated with vemurafenib monotherapy. | Total of all reporting groups |
| Overall Participants | 62 | 4 | 10 | 27 | 9 | 9 | 26 | 12 | 12 | 9 | 28 | 208 |
| Age (years) [Mean (Standard Deviation) ] | ||||||||||||
| Mean (Standard Deviation) [years] |
65.4
(10.2)
|
45.8
(5.3)
|
57.3
(5.4)
|
64.3
(8.8)
|
53.2
(9.7)
|
62.1
(4.3)
|
60.8
(13.3)
|
66.8
(9.2)
|
41.6
(12.2)
|
34.3
(20.7)
|
53.7
(17.5)
|
59.0
(14.5)
|
| Sex: Female, Male (Count of Participants) | ||||||||||||
| Female |
27
43.5%
|
4
100%
|
5
50%
|
18
66.7%
|
5
55.6%
|
3
33.3%
|
14
53.8%
|
3
25%
|
8
66.7%
|
9
100%
|
15
53.6%
|
111
53.4%
|
| Male |
35
56.5%
|
0
0%
|
5
50%
|
9
33.3%
|
4
44.4%
|
6
66.7%
|
12
46.2%
|
9
75%
|
4
33.3%
|
0
0%
|
13
46.4%
|
97
46.6%
|
Outcome Measures
| Title | Confirmed Best Overall Response Rate (BORR) |
|---|---|
| Description | Confirmed BORR: percentage of participants with an objective response (OR) (complete response [CR], partial response [PR], stringent CR [sCR] or very good PR [VGPR]) on 2 occasions >/= 4 weeks apart as assessed by the Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. or International Myeloma Working Group (IMWG) criteria. RECIST v1.1: CR: disappearance of all target lesions; PR: >/= 30% decrease in the sum of diameters of target lesions. IMWG: CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and </= 5% plasma cells in bone marrow; PR: >/= 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >/= 90% or to <200 mg per 24 hours. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or >/= 90% reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hour; sCR: CR plus normal free light chain (FLC) ratio and no clonal cells in bone marrow. |
| Time Frame | Up to approximately 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants enrolled in the study irrespective of whether they had received study drug or not. |
| Arm/Group Title | Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - Vemurafenib | Cohort 2: Ovarian Cancer - Vemurafenib | Cohort 3a: Colorectal Cancer - Vemurafenib | Cohort 3b: Colorectal Cancer - Vemurafenib + Cetuximab | Cohort 4: Cholangiocarcinoma - Vemurafenib | Cohort 6: Multiple Myeloma - Vemurafenib | Cohort 7a: ECD/LCH - Vemurafenib | Cohort 7b: Anaplastic Thyroid Cancer - Vemurafenib | Cohort 7c: Advanced Stage Astrocytoma - Vemurafenib | Cohort 7d: Early Stage Astrocytoma - Vemurafenib | Cohort 7: Other BRAF V600-positive Tumors - Vemurafenib |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with NSCLC were treated with vemurafenib monotherapy. | Participants with ovarian cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib and cetuximab combination therapy. | Participants with cholangiocarcinoma were treated with vemurafenib monotherapy. | Participants with multiple myeloma were treated with vemurafenib monotherapy. | Participants with Erdheim-Chester disease (ECD) or Langerhans cell histiocytosis (LCH) were treated with vemurafenib monotherapy. | Participants with anaplastic thyroid cancer were treated with vemurafenib monotherapy. | Participants with advanced stage astrocytoma were treated with vemurafenib monotherapy. | Participants with early stage astrocytoma were treated with vemurafenib monotherapy. | Participants with other BRAF V600-positive tumors were treated with vemurafenib monotherapy. |
| Measure Participants | 62 | 4 | 10 | 27 | 9 | 9 | 26 | 12 | 12 | 9 | 28 |
| Number (95% Confidence Interval) [percentage of participants] |
37.1
59.8%
|
50.0
1250%
|
0
0%
|
7.4
27.4%
|
22.2
246.7%
|
22.2
246.7%
|
61.5
236.5%
|
25.0
208.3%
|
16.7
139.2%
|
33.3
370%
|
17.9
63.9%
|
| Title | Percentage of Participants With Confirmed Clinical Benefit |
|---|---|
| Description | Included were participants with confirmed PR or CR or Stable Disease (SD) that had lasted at least 6 months according to RECIST v1.1 or confirmed CR, PR, VGPR, sCR or SD for at least 6 months according to IMWG criteria. RECIST v1.1: PR: >/= 30% decrease in the sum of diameters of target lesions; CR: disappearance of all target lesions; SD: not meeting criteria for CR, PR or progressive disease (PD). IMWG: CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and </= 5% plasma cells in bone marrow; PR: >/= 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >/= 90% or to <200 mg per 24 hours. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or >/= 90% reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hour; sCR: CR plus normal FLC ratio and no clonal cells in bone marrow; SD: not meeting criteria for CR, VGPR, PR or PD. |
| Time Frame | Up to approximately 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants enrolled in the study irrespective of whether they had received study medication or not. |
| Arm/Group Title | Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - Vemurafenib | Cohort 2: Ovarian Cancer - Vemurafenib | Cohort 3a: Colorectal Cancer - Vemurafenib | Cohort 3b: Colorectal Cancer - Vemurafenib + Cetuximab | Cohort 4: Cholangiocarcinoma - Vemurafenib | Cohort 6: Multiple Myeloma - Vemurafenib | Cohort 7a: ECD/LCH - Vemurafenib | Cohort 7b: Anaplastic Thyroid Cancer - Vemurafenib | Cohort 7c: Advanced Stage Astrocytoma - Vemurafenib | Cohort 7d: Early Stage Astrocytoma - Vemurafenib | Cohort 7: Other BRAF V600-positive Tumors - Vemurafenib |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with NSCLC were treated with vemurafenib monotherapy. | Participants with ovarian cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib and cetuximab combination therapy. | Participants with cholangiocarcinoma were treated with vemurafenib monotherapy. | Participants with multiple myeloma were treated with vemurafenib monotherapy. | Participants with Erdheim-Chester disease (ECD) or Langerhans cell histiocytosis (LCH) were treated with vemurafenib monotherapy. | Participants with anaplastic thyroid cancer were treated with vemurafenib monotherapy. | Participants with advanced stage astrocytoma were treated with vemurafenib monotherapy. | Participants with early stage astrocytoma were treated with vemurafenib monotherapy. | Participants with other BRAF V600-positive tumors were treated with vemurafenib monotherapy. |
| Measure Participants | 62 | 4 | 10 | 27 | 9 | 9 | 26 | 12 | 12 | 9 | 28 |
| Number (95% Confidence Interval) [percentage of participants] |
48.4
78.1%
|
50.0
1250%
|
0
0%
|
18.5
68.5%
|
44.4
493.3%
|
22.2
246.7%
|
76.9
295.8%
|
25.0
208.3%
|
33.3
277.5%
|
44.4
493.3%
|
17.9
63.9%
|
| Title | Overall Response Rate (ORR) |
|---|---|
| Description | ORR: percentage of participants with an objective response (OR) (CR, PR, sCR or VGPR) on 2 occasions >/= 4 weeks apart as assessed by the Investigator using RECIST v1.1. or IMWG criteria. RECIST v1.1: CR: disappearance of all target lesions; PR: >/= 30% decrease in the sum of diameters of target lesions. IMWG: CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and </= 5% plasma cells in bone marrow; PR: >/= 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >/= 90% or to <200 mg per 24 hours. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or >/= 90% reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hour; sCR: CR plus normal FLC ratio and no clonal cells in bone marrow. |
| Time Frame | Up to approximately 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants enrolled in the study irrespective of whether they had received study medication or not. |
| Arm/Group Title | Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - Vemurafenib | Cohort 2: Ovarian Cancer - Vemurafenib | Cohort 3a: Colorectal Cancer - Vemurafenib | Cohort 3b: Colorectal Cancer - Vemurafenib + Cetuximab | Cohort 4: Cholangiocarcinoma - Vemurafenib | Cohort 6: Multiple Myeloma - Vemurafenib | Cohort 7a: ECD/LCH - Vemurafenib | Cohort 7b: Anaplastic Thyroid Cancer - Vemurafenib | Cohort 7c: Advanced Stage Astrocytoma - Vemurafenib | Cohort 7d: Early Stage Astrocytoma - Vemurafenib | Cohort 7: Other BRAF V600-positive Tumors - Vemurafenib |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with NSCLC were treated with vemurafenib monotherapy. | Participants with ovarian cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib and cetuximab combination therapy. | Participants with cholangiocarcinoma were treated with vemurafenib monotherapy. | Participants with multiple myeloma were treated with vemurafenib monotherapy. | Participants with Erdheim-Chester disease (ECD) or Langerhans cell histiocytosis (LCH) were treated with vemurafenib monotherapy. | Participants with anaplastic thyroid cancer were treated with vemurafenib monotherapy. | Participants with advanced stage astrocytoma were treated with vemurafenib monotherapy. | Participants with early stage astrocytoma were treated with vemurafenib monotherapy. | Participants with other BRAF V600-positive tumors were treated with vemurafenib monotherapy. |
| Measure Participants | 62 | 4 | 10 | 27 | 9 | 9 | 26 | 12 | 12 | 9 | 28 |
| CR |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
7.7
29.6%
|
8.3
69.2%
|
8.3
69.2%
|
0
0%
|
3.6
12.9%
|
| PR |
37.1
59.8%
|
50.0
1250%
|
0
0%
|
7.4
27.4%
|
22.2
246.7%
|
11.1
123.3%
|
53.8
206.9%
|
16.7
139.2%
|
8.3
69.2%
|
33.3
370%
|
14.3
51.1%
|
| VGPR |
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
11.1
123.3%
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
| sCR |
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
0
0%
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | DOR was defined as the period from the date of initial PR or CR for solid tumors according to RECISTv1.1 and CR, PR, VGPR or sCR for multiple myeloma according to IMWG criteria, until the date of PD or death from any cause. RECIST v1.1: PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. IMWG: PD: increase of >/= 25% from lowest response value in serum or urine M-protein or bone marrow plasma cell percentage or development of new or increase in size of bone lesions or soft tissue plasmacytomas. |
| Time Frame | Up to approximately 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants enrolled in the study irrespective of whether they had received study medication or not. |
| Arm/Group Title | Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - Vemurafenib | Cohort 2: Ovarian Cancer - Vemurafenib | Cohort 3a: Colorectal Cancer - Vemurafenib | Cohort 3b: Colorectal Cancer - Vemurafenib + Cetuximab | Cohort 4: Cholangiocarcinoma - Vemurafenib | Cohort 6: Multiple Myeloma - Vemurafenib | Cohort 7a: ECD/LCH - Vemurafenib | Cohort 7b: Anaplastic Thyroid Cancer - Vemurafenib | Cohort 7c: Advanced Stage Astrocytoma - Vemurafenib | Cohort 7d: Early Stage Astrocytoma - Vemurafenib | Cohort 7: Other BRAF V600-positive Tumors - Vemurafenib |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with NSCLC were treated with vemurafenib monotherapy. | Participants with ovarian cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib and cetuximab combination therapy. | Participants with cholangiocarcinoma were treated with vemurafenib monotherapy. | Participants with multiple myeloma were treated with vemurafenib monotherapy. | Participants with Erdheim-Chester disease (ECD) or Langerhans cell histiocytosis (LCH) were treated with vemurafenib monotherapy. | Participants with anaplastic thyroid cancer were treated with vemurafenib monotherapy. | Participants with advanced stage astrocytoma were treated with vemurafenib monotherapy. | Participants with early stage astrocytoma were treated with vemurafenib monotherapy. | Participants with other BRAF V600-positive tumors were treated with vemurafenib monotherapy. |
| Measure Participants | 62 | 4 | 10 | 27 | 9 | 9 | 26 | 12 | 12 | 9 | 28 |
| Median (95% Confidence Interval) [months] |
7.16
|
8.16
|
NA
|
6.54
|
12.86
|
NA
|
NA
|
9.95
|
NA
|
3.42
|
9.92
|
| Title | Time to Response |
|---|---|
| Description | Time to response was defined as the time from the first day of study treatment to the date of first CR, or PR for solid tumors according to RECISTv1.1 and CR, PR, VGPR or sCR for multiple myeloma according to IMWG criteria. RECIST v1.1: CR: disappearance of all target lesions; PR: at least a 30% decrease in the sum of diameters of target lesions. IMWG criteria: CR: negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and </= 5% plasma cells in bone marrow; PR: >/= 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >/= 90% or to < 200 mg per 24 hours. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or >/= 90% reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hour; sCR: CR plus normal FLC ratio and no clonal cells in bone marrow. |
| Time Frame | Up to approximately 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants enrolled in the study irrespective of whether they had received study medication or not. |
| Arm/Group Title | Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - Vemurafenib | Cohort 2: Ovarian Cancer - Vemurafenib | Cohort 3a: Colorectal Cancer - Vemurafenib | Cohort 3b: Colorectal Cancer - Vemurafenib + Cetuximab | Cohort 4: Cholangiocarcinoma - Vemurafenib | Cohort 6: Multiple Myeloma - Vemurafenib | Cohort 7a: ECD/LCH - Vemurafenib | Cohort 7b: Anaplastic Thyroid Cancer - Vemurafenib | Cohort 7c: Advanced Stage Astrocytoma - Vemurafenib | Cohort 7d: Early Stage Astrocytoma - Vemurafenib | Cohort 7: Other BRAF V600-positive Tumors - Vemurafenib |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with NSCLC were treated with vemurafenib monotherapy. | Participants with ovarian cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib and cetuximab combination therapy. | Participants with cholangiocarcinoma were treated with vemurafenib monotherapy. | Participants with multiple myeloma were treated with vemurafenib monotherapy. | Participants with Erdheim-Chester disease (ECD) or Langerhans cell histiocytosis (LCH) were treated with vemurafenib monotherapy. | Participants with anaplastic thyroid cancer were treated with vemurafenib monotherapy. | Participants with advanced stage astrocytoma were treated with vemurafenib monotherapy. | Participants with early stage astrocytoma were treated with vemurafenib monotherapy. | Participants with other BRAF V600-positive tumors were treated with vemurafenib monotherapy. |
| Measure Participants | 62 | 4 | 10 | 27 | 9 | 9 | 26 | 12 | 12 | 9 | 28 |
| Median (95% Confidence Interval) [months] |
7.26
|
NA
|
NA
|
NA
|
NA
|
5.75
|
5.49
|
NA
|
NA
|
NA
|
NA
|
| Title | Time to Tumor Progression (TTP) |
|---|---|
| Description | TTP was defined as time from the first day of study treatment to the first occurrence of progressive disease (PD). RECIST v1.1: PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. IMWG: PD: increase of >/= 25% from lowest response value in serum or urine M-protein or bone marrow plasma cell percentage or development of new or increase in size of bone lesions or soft tissue plasmacytomas. |
| Time Frame | Up to approximately 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants enrolled in the study irrespective of whether they had received study medication or not. |
| Arm/Group Title | Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - Vemurafenib | Cohort 2: Ovarian Cancer - Vemurafenib | Cohort 3a: Colorectal Cancer - Vemurafenib | Cohort 3b: Colorectal Cancer - Vemurafenib + Cetuximab | Cohort 4: Cholangiocarcinoma - Vemurafenib | Cohort 6: Multiple Myeloma - Vemurafenib | Cohort 7a: ECD/LCH - Vemurafenib | Cohort 7b: Anaplastic Thyroid Cancer - Vemurafenib | Cohort 7c: Advanced Stage Astrocytoma - Vemurafenib | Cohort 7d: Early Stage Astrocytoma - Vemurafenib | Cohort 7: Other BRAF V600-positive Tumors - Vemurafenib |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with NSCLC were treated with vemurafenib monotherapy. | Participants with ovarian cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib and cetuximab combination therapy. | Participants with cholangiocarcinoma were treated with vemurafenib monotherapy. | Participants with multiple myeloma were treated with vemurafenib monotherapy. | Participants with Erdheim-Chester disease (ECD) or Langerhans cell histiocytosis (LCH) were treated with vemurafenib monotherapy. | Participants with anaplastic thyroid cancer were treated with vemurafenib monotherapy. | Participants with advanced stage astrocytoma were treated with vemurafenib monotherapy. | Participants with early stage astrocytoma were treated with vemurafenib monotherapy. | Participants with other BRAF V600-positive tumors were treated with vemurafenib monotherapy. |
| Measure Participants | 62 | 4 | 10 | 27 | 9 | 9 | 26 | 12 | 12 | 9 | 28 |
| Median (95% Confidence Interval) [months] |
7.33
|
6.44
|
3.88
|
3.68
|
3.02
|
4.63
|
NA
|
2.83
|
5.62
|
5.36
|
3.65
|
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | PFS was defined as the time from the first day of study treatment, until the first documented PD or death from any cause, whichever occurs first. RECIST v1.1: PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. IMWG criteria: PD: increase of >/= 25% from lowest response value in serum or urine M-protein or bone marrow plasma cell percentage or development of new or increase in size of bone lesions or soft tissue plasmacytomas. |
| Time Frame | Up to approximately 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants enrolled in the study irrespective of whether they had received study medication or not. |
| Arm/Group Title | Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - Vemurafenib | Cohort 2: Ovarian Cancer - Vemurafenib | Cohort 3a: Colorectal Cancer - Vemurafenib | Cohort 3b: Colorectal Cancer - Vemurafenib + Cetuximab | Cohort 4: Cholangiocarcinoma - Vemurafenib | Cohort 6: Multiple Myeloma - Vemurafenib | Cohort 7a: ECD/LCH - Vemurafenib | Cohort 7b: Anaplastic Thyroid Cancer - Vemurafenib | Cohort 7c: Advanced Stage Astrocytoma - Vemurafenib | Cohort 7d: Early Stage Astrocytoma - Vemurafenib | Cohort 7: Other BRAF V600-positive Tumors - Vemurafenib |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with NSCLC were treated with vemurafenib monotherapy. | Participants with ovarian cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib and cetuximab combination therapy. | Participants with cholangiocarcinoma were treated with vemurafenib monotherapy. | Participants with multiple myeloma were treated with vemurafenib monotherapy. | Participants with Erdheim-Chester disease (ECD) or Langerhans cell histiocytosis (LCH) were treated with vemurafenib monotherapy. | Participants with anaplastic thyroid cancer were treated with vemurafenib monotherapy. | Participants with advanced stage astrocytoma were treated with vemurafenib monotherapy. | Participants with early stage astrocytoma were treated with vemurafenib monotherapy. | Participants with other BRAF V600-positive tumors were treated with vemurafenib monotherapy. |
| Measure Participants | 62 | 4 | 10 | 27 | 9 | 9 | 26 | 12 | 12 | 9 | 28 |
| Median (95% Confidence Interval) [months] |
6.51
|
6.44
|
3.88
|
3.68
|
3.02
|
4.63
|
NA
|
2.83
|
9.59
|
5.26
|
3.12
|
| Title | Overall Survival (OS) |
|---|---|
| Description | OS was defined as time between the first day of study treatment and date of death of any cause. |
| Time Frame | Up to approximately 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants enrolled in the study irrespective of whether they had received study medication or not. |
| Arm/Group Title | Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - Vemurafenib | Cohort 2: Ovarian Cancer - Vemurafenib | Cohort 3a: Colorectal Cancer - Vemurafenib | Cohort 3b: Colorectal Cancer - Vemurafenib + Cetuximab | Cohort 4: Cholangiocarcinoma - Vemurafenib | Cohort 6: Multiple Myeloma - Vemurafenib | Cohort 7a: ECD/LCH - Vemurafenib | Cohort 7b: Anaplastic Thyroid Cancer - Vemurafenib | Cohort 7c: Advanced Stage Astrocytoma - Vemurafenib | Cohort 7d: Early Stage Astrocytoma - Vemurafenib | Cohort 7: Other BRAF V600-positive Tumors - Vemurafenib |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with NSCLC were treated with vemurafenib monotherapy. | Participants with ovarian cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib and cetuximab combination therapy. | Participants with cholangiocarcinoma were treated with vemurafenib monotherapy. | Participants with multiple myeloma were treated with vemurafenib monotherapy. | Participants with Erdheim-Chester disease (ECD) or Langerhans cell histiocytosis (LCH) were treated with vemurafenib monotherapy. | Participants with anaplastic thyroid cancer were treated with vemurafenib monotherapy. | Participants with advanced stage astrocytoma were treated with vemurafenib monotherapy. | Participants with early stage astrocytoma were treated with vemurafenib monotherapy. | Participants with other BRAF V600-positive tumors were treated with vemurafenib monotherapy. |
| Measure Participants | 62 | 4 | 10 | 27 | 9 | 9 | 26 | 12 | 12 | 9 | 28 |
| Median (95% Confidence Interval) [months] |
15.38
|
NA
|
9.30
|
7.16
|
17.94
|
24.54
|
NA
|
5.88
|
40.11
|
12.75
|
11.56
|
| Title | Maximum Tolerated Dose for Vemurafenib in Combination With Cetuximab |
|---|---|
| Description | Cohort 3b included participants with colorectal cancer treated with escalating doses of vemurafenib and cetuximab. The escalating doses were as follows: Dose Level 1: 720 milligrams (mg) of vemurafenib orally twice daily starting on Day 2 of Cycle 1 and 300 milligrams per square meter (mg/m^2) loading dose of cetuximab by infusion and then 200 mg/m^2 weekly; Dose Level 2: 720 mg of vemurafenib twice daily starting on Day 2 of Cycle 1 and 400 mg/m^2 loading dose of cetuximab and then 250 mg/m^2 weekly; Dose Level 3: 960 mg of vemurafenib twice daily starting on Day 2 of Cycle 1 and 400 mg/m^2 loading dose of cetuximab and then 250 mg/m^2 weekly. Reported here are the maximum tolerated doses for each vemurafenib and cetuximab. |
| Time Frame | Up to approximately 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants from Cohort 3b who received at least one dose of study medication. |
| Arm/Group Title | Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - Vemurafenib | Cohort 2: Ovarian Cancer - Vemurafenib | Cohort 3a: Colorectal Cancer - Vemurafenib | Cohort 3b: Colorectal Cancer - Vemurafenib + Cetuximab | Cohort 4: Cholangiocarcinoma - Vemurafenib | Cohort 6: Multiple Myeloma - Vemurafenib | Cohort 7a: ECD/LCH - Vemurafenib | Cohort 7b: Anaplastic Thyroid Cancer - Vemurafenib | Cohort 7c: Advanced Stage Astrocytoma - Vemurafenib | Cohort 7d: Early Stage Astrocytoma - Vemurafenib | Cohort 7: Other BRAF V600-positive Tumors - Vemurafenib |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with NSCLC were treated with vemurafenib monotherapy. | Participants with ovarian cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib and cetuximab combination therapy. | Participants with cholangiocarcinoma were treated with vemurafenib monotherapy. | Participants with multiple myeloma were treated with vemurafenib monotherapy. | Participants with Erdheim-Chester disease (ECD) or Langerhans cell histiocytosis (LCH) were treated with vemurafenib monotherapy. | Participants with anaplastic thyroid cancer were treated with vemurafenib monotherapy. | Participants with advanced stage astrocytoma were treated with vemurafenib monotherapy. | Participants with early stage astrocytoma were treated with vemurafenib monotherapy. | Participants with other BRAF V600-positive tumors were treated with vemurafenib monotherapy. |
| Measure Participants | 0 | 0 | 0 | 14 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| vemurafenib |
960
|
||||||||||
| cetuximab |
400
|
| Title | Number of Dose-limiting Toxicities of Vemurafenib in Combination With Cetuximab |
|---|---|
| Description | Cohort 3b included participants with colorectal cancer treated with escalating doses of vemurafenib and cetuximab. The escalating doses were as follows: Dose Level 1: 720 milligrams (mg) of vemurafenib orally twice daily starting on Day 2 of Cycle 1 and 300 milligrams per square meter (mg/m^2) loading dose of cetuximab by infusion and then 200 mg/m^2 weekly; Dose Level 2: 720 mg of vemurafenib twice daily starting on Day 2 of Cycle 1 and 400 mg/m^2 loading dose of cetuximab and then 250 mg/m^2 weekly; Dose Level 3: 960 mg of vemurafenib twice daily starting on Day 2 of Cycle 1 and 400 mg/m^2 loading dose of cetuximab and then 250 mg/m^2 weekly. Reported here are type and number of dose limited toxicities observed. |
| Time Frame | Up to 28 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants from Cohort 3b who received at least one dose of study medication. |
| Arm/Group Title | Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - Vemurafenib | Cohort 2: Ovarian Cancer - Vemurafenib | Cohort 3a: Colorectal Cancer - Vemurafenib | Cohort 3b: Colorectal Cancer - Vemurafenib + Cetuximab | Cohort 4: Cholangiocarcinoma - Vemurafenib | Cohort 6: Multiple Myeloma - Vemurafenib | Cohort 7a: ECD/LCH - Vemurafenib | Cohort 7b: Anaplastic Thyroid Cancer - Vemurafenib | Cohort 7c: Advanced Stage Astrocytoma - Vemurafenib | Cohort 7d: Early Stage Astrocytoma - Vemurafenib | Cohort 7: Other BRAF V600-positive Tumors - Vemurafenib |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with NSCLC were treated with vemurafenib monotherapy. | Participants with ovarian cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib and cetuximab combination therapy. | Participants with cholangiocarcinoma were treated with vemurafenib monotherapy. | Participants with multiple myeloma were treated with vemurafenib monotherapy. | Participants with Erdheim-Chester disease (ECD) or Langerhans cell histiocytosis (LCH) were treated with vemurafenib monotherapy. | Participants with anaplastic thyroid cancer were treated with vemurafenib monotherapy. | Participants with advanced stage astrocytoma were treated with vemurafenib monotherapy. | Participants with early stage astrocytoma were treated with vemurafenib monotherapy. | Participants with other BRAF V600-positive tumors were treated with vemurafenib monotherapy. |
| Measure Participants | 0 | 0 | 0 | 14 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Grade 3 amylase increased |
1
|
||||||||||
| Grade 4 lipase increased |
1
|
| Title | Safety: Percentage of Participants With Adverse Event |
|---|---|
| Description | An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. |
| Time Frame | Up to approximately 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all participants who received at least one dose of study medication. |
| Arm/Group Title | Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - Vemurafenib | Cohort 2: Ovarian Cancer - Vemurafenib | Cohort 3a: Colorectal Cancer - Vemurafenib | Cohort 3b: Colorectal Cancer - Vemurafenib + Cetuximab | Cohort 4: Cholangiocarcinoma - Vemurafenib | Cohort 6: Multiple Myeloma - Vemurafenib | Cohort 7a: ECD/LCH - Vemurafenib | Cohort 7b: Anaplastic Thyroid Cancer - Vemurafenib | Cohort 7c: Advanced Stage Astrocytoma - Vemurafenib | Cohort 7d: Early Stage Astrocytoma - Vemurafenib | Cohort 7: Other BRAF V600-positive Tumors - Vemurafenib |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with NSCLC were treated with vemurafenib monotherapy. | Participants with ovarian cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib monotherapy. | Participants with colorectal cancer were treated with vemurafenib and cetuximab combination therapy. | Participants with cholangiocarcinoma were treated with vemurafenib monotherapy. | Participants with multiple myeloma were treated with vemurafenib monotherapy. | Participants with Erdheim-Chester disease (ECD) or Langerhans cell histiocytosis (LCH) were treated with vemurafenib monotherapy. | Participants with anaplastic thyroid cancer were treated with vemurafenib monotherapy. | Participants with advanced stage astrocytoma were treated with vemurafenib monotherapy. | Participants with early stage astrocytoma were treated with vemurafenib monotherapy. | Participants with other BRAF V600-positive tumors were treated with vemurafenib monotherapy. |
| Measure Participants | 62 | 4 | 10 | 27 | 9 | 9 | 26 | 12 | 12 | 9 | 28 |
| Number [percentage of participants] |
100
161.3%
|
100
2500%
|
100
1000%
|
100
370.4%
|
100
1111.1%
|
100
1111.1%
|
100
384.6%
|
91.7
764.2%
|
100
833.3%
|
100
1111.1%
|
100
357.1%
|
Adverse Events
| Time Frame | From baseline up to approximately 3 years | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The safety population included all participants who received at least one dose of study medication. | |||
| Arm/Group Title | Cohort 3b: Colorectal Cancer - Vemurafenib + Cetuximab | Pooled Arm - Vemurafenib | ||
| Arm/Group Description | Participants with colorectal cancer were treated with vemurafenib and cetuximab combination therapy. | Participants with a variety of cancer types, who were treated with vemurafenib monotherapy, were combined into this arm. | ||
All Cause Mortality |
||||
| Cohort 3b: Colorectal Cancer - Vemurafenib + Cetuximab | Pooled Arm - Vemurafenib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Cohort 3b: Colorectal Cancer - Vemurafenib + Cetuximab | Pooled Arm - Vemurafenib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/27 (40.7%) | 91/181 (50.3%) | ||
| Blood and lymphatic system disorders | ||||
| Pseudolymphoma | 0/27 (0%) | 1/181 (0.6%) | ||
| Splenic infarction | 0/27 (0%) | 1/181 (0.6%) | ||
| Cardiac disorders | ||||
| Acute coronary syndrome | 0/27 (0%) | 2/181 (1.1%) | ||
| Pericarditis | 0/27 (0%) | 2/181 (1.1%) | ||
| Dressler's syndrome | 0/27 (0%) | 1/181 (0.6%) | ||
| Myocardial infarction | 0/27 (0%) | 1/181 (0.6%) | ||
| Pericardial effusion | 0/27 (0%) | 1/181 (0.6%) | ||
| Eye disorders | ||||
| Iridocyclitis | 0/27 (0%) | 1/181 (0.6%) | ||
| Gastrointestinal disorders | ||||
| Upper gastrointestinal haemorrhage | 1/27 (3.7%) | 1/181 (0.6%) | ||
| Subileus | 1/27 (3.7%) | 0/181 (0%) | ||
| Duodenal perforation | 0/27 (0%) | 1/181 (0.6%) | ||
| Dysphagia | 0/27 (0%) | 1/181 (0.6%) | ||
| Gastric ulcer | 0/27 (0%) | 1/181 (0.6%) | ||
| Stomatitis | 0/27 (0%) | 1/181 (0.6%) | ||
| General disorders | ||||
| Non-cardiac chest pain | 1/27 (3.7%) | 0/181 (0%) | ||
| Pyrexia | 1/27 (3.7%) | 2/181 (1.1%) | ||
| Fatigue | 0/27 (0%) | 2/181 (1.1%) | ||
| Chest pain | 0/27 (0%) | 1/181 (0.6%) | ||
| Hyperthermia | 0/27 (0%) | 1/181 (0.6%) | ||
| Hepatobiliary disorders | ||||
| Cholestasis | 1/27 (3.7%) | 0/181 (0%) | ||
| Bile duct obstruction | 0/27 (0%) | 1/181 (0.6%) | ||
| Drug-induced liver injury | 0/27 (0%) | 1/181 (0.6%) | ||
| Immune system disorders | ||||
| Hypersensitivity | 0/27 (0%) | 1/181 (0.6%) | ||
| Infections and infestations | ||||
| Sepsis | 0/27 (0%) | 6/181 (3.3%) | ||
| Pneumonia | 0/27 (0%) | 5/181 (2.8%) | ||
| Lung infection | 0/27 (0%) | 4/181 (2.2%) | ||
| Bronchitis | 0/27 (0%) | 3/181 (1.7%) | ||
| Lower respiratory tract infection | 0/27 (0%) | 2/181 (1.1%) | ||
| Abdominal abscess | 0/27 (0%) | 1/181 (0.6%) | ||
| Bacteraemia | 0/27 (0%) | 1/181 (0.6%) | ||
| Cellulitis | 0/27 (0%) | 1/181 (0.6%) | ||
| Diverticulitis | 0/27 (0%) | 1/181 (0.6%) | ||
| Furuncle | 0/27 (0%) | 1/181 (0.6%) | ||
| Septic shock | 0/27 (0%) | 1/181 (0.6%) | ||
| Soft tissue infection | 0/27 (0%) | 1/181 (0.6%) | ||
| Staphylococcal sepsis | 0/27 (0%) | 1/181 (0.6%) | ||
| Urinary tract infection | 0/27 (0%) | 1/181 (0.6%) | ||
| Injury, poisoning and procedural complications | ||||
| Femoral neck fracture | 1/27 (3.7%) | 0/181 (0%) | ||
| Fracture | 0/27 (0%) | 1/181 (0.6%) | ||
| Limb injury | 0/27 (0%) | 1/181 (0.6%) | ||
| Subdural haematoma | 0/27 (0%) | 1/181 (0.6%) | ||
| Investigations | ||||
| Gamma-glutamyltransferase increased | 1/27 (3.7%) | 0/181 (0%) | ||
| Body temperature increased | 0/27 (0%) | 1/181 (0.6%) | ||
| Metabolism and nutrition disorders | ||||
| Diabetes mellitus | 0/27 (0%) | 1/181 (0.6%) | ||
| Glucose tolerance impaired | 0/27 (0%) | 1/181 (0.6%) | ||
| Hypercalcaemia | 0/27 (0%) | 1/181 (0.6%) | ||
| Dehydration | 0/27 (0%) | 3/181 (1.7%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 0/27 (0%) | 1/181 (0.6%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Squamous cell carcinoma of skin | 3/27 (11.1%) | 25/181 (13.8%) | ||
| Keratoacanthoma | 2/27 (7.4%) | 18/181 (9.9%) | ||
| Basal cell carcinoma | 1/27 (3.7%) | 7/181 (3.9%) | ||
| Squamous cell carcinoma | 1/27 (3.7%) | 1/181 (0.6%) | ||
| Bowen's disease | 0/27 (0%) | 4/181 (2.2%) | ||
| Chronic myelomonocytic leukaemia | 0/27 (0%) | 1/181 (0.6%) | ||
| Papillary thyroid cancer | 0/27 (0%) | 1/181 (0.6%) | ||
| Paraganglion neoplasm | 0/27 (0%) | 1/181 (0.6%) | ||
| Skin cancer | 0/27 (0%) | 1/181 (0.6%) | ||
| Squamous cell carcinoma of lung | 0/27 (0%) | 1/181 (0.6%) | ||
| Nervous system disorders | ||||
| Aphasia | 0/27 (0%) | 1/181 (0.6%) | ||
| Brain oedema | 0/27 (0%) | 1/181 (0.6%) | ||
| Haemorrhagic stroke | 0/27 (0%) | 1/181 (0.6%) | ||
| Partial seizures | 0/27 (0%) | 1/181 (0.6%) | ||
| Peripheral motor neuropathy | 0/27 (0%) | 1/181 (0.6%) | ||
| Posterior reversible encephalopathy syndrome | 0/27 (0%) | 1/181 (0.6%) | ||
| Seizure | 0/27 (0%) | 1/181 (0.6%) | ||
| Transient ischaemic attack | 0/27 (0%) | 1/181 (0.6%) | ||
| Psychiatric disorders | ||||
| Delirium | 0/27 (0%) | 1/181 (0.6%) | ||
| Depression | 0/27 (0%) | 1/181 (0.6%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 1/27 (3.7%) | 4/181 (2.2%) | ||
| Bladder dilatation | 1/27 (3.7%) | 0/181 (0%) | ||
| Obstructive uropathy | 1/27 (3.7%) | 0/181 (0%) | ||
| Renal failure | 0/27 (0%) | 1/181 (0.6%) | ||
| Reproductive system and breast disorders | ||||
| Prostatitis | 0/27 (0%) | 2/181 (1.1%) | ||
| Benign prostatic hyperplasia | 0/27 (0%) | 1/181 (0.6%) | ||
| Uterine haemorrhage | 0/27 (0%) | 1/181 (0.6%) | ||
| Vaginal haemorrhage | 0/27 (0%) | 1/181 (0.6%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Pulmonary thrombosis | 1/27 (3.7%) | 0/181 (0%) | ||
| Dyspnoea | 0/27 (0%) | 3/181 (1.7%) | ||
| Pulmonary embolism | 0/27 (0%) | 3/181 (1.7%) | ||
| Respiratory failure | 0/27 (0%) | 2/181 (1.1%) | ||
| Laryngeal dyspnoea | 0/27 (0%) | 1/181 (0.6%) | ||
| Pleural effusion | 0/27 (0%) | 1/181 (0.6%) | ||
| Pneumothorax | 0/27 (0%) | 1/181 (0.6%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Acute febrile neutrophilic dermatosis | 0/27 (0%) | 1/181 (0.6%) | ||
| Rash | 0/27 (0%) | 1/181 (0.6%) | ||
| Skin lesion | 0/27 (0%) | 1/181 (0.6%) | ||
| Vascular disorders | ||||
| Jugular vein thrombosis | 0/27 (0%) | 1/181 (0.6%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Cohort 3b: Colorectal Cancer - Vemurafenib + Cetuximab | Pooled Arm - Vemurafenib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 26/27 (96.3%) | 177/181 (97.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 3/27 (11.1%) | 30/181 (16.6%) | ||
| Eye disorders | ||||
| Dry eye | 0/27 (0%) | 11/181 (6.1%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 12/27 (44.4%) | 12/181 (6.6%) | ||
| Abdominal pain upper | 4/27 (14.8%) | 0/181 (0%) | ||
| Constipation | 5/27 (18.5%) | 26/181 (14.4%) | ||
| Diarrhoea | 13/27 (48.1%) | 49/181 (27.1%) | ||
| Dyspepsia | 2/27 (7.4%) | 0/181 (0%) | ||
| Flatulence | 2/27 (7.4%) | 0/181 (0%) | ||
| Nausea | 9/27 (33.3%) | 54/181 (29.8%) | ||
| Rectal haemorrhage | 2/27 (7.4%) | 0/181 (0%) | ||
| Stomatitis | 4/27 (14.8%) | 19/181 (10.5%) | ||
| Vomiting | 8/27 (29.6%) | 41/181 (22.7%) | ||
| Dry mouth | 0/27 (0%) | 12/181 (6.6%) | ||
| Dysphagia | 0/27 (0%) | 14/181 (7.7%) | ||
| General disorders | ||||
| Asthenia | 10/27 (37%) | 39/181 (21.5%) | ||
| Chest pain | 2/27 (7.4%) | 0/181 (0%) | ||
| Chills | 2/27 (7.4%) | 10/181 (5.5%) | ||
| Fatigue | 6/27 (22.2%) | 60/181 (33.1%) | ||
| Oedema peripheral | 4/27 (14.8%) | 21/181 (11.6%) | ||
| Pyrexia | 5/27 (18.5%) | 26/181 (14.4%) | ||
| Cyst | 0/27 (0%) | 21/181 (11.6%) | ||
| Xerosis | 0/27 (0%) | 16/181 (8.8%) | ||
| Hepatobiliary disorders | ||||
| Hyperbilirubinaemia | 0/27 (0%) | 11/181 (6.1%) | ||
| Infections and infestations | ||||
| Conjunctivitis | 3/27 (11.1%) | 0/181 (0%) | ||
| Folliculitis | 3/27 (11.1%) | 18/181 (9.9%) | ||
| Oral candidiasis | 2/27 (7.4%) | 0/181 (0%) | ||
| Rash pustular | 3/27 (11.1%) | 0/181 (0%) | ||
| Skin infection | 2/27 (7.4%) | 0/181 (0%) | ||
| Urinary tract infection | 3/27 (11.1%) | 0/181 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Fall | 2/27 (7.4%) | 0/181 (0%) | ||
| Sunburn | 4/27 (14.8%) | 22/181 (12.2%) | ||
| Investigations | ||||
| Amylase increased | 6/27 (22.2%) | 0/181 (0%) | ||
| Aspartate aminotransferase increased | 2/27 (7.4%) | 15/181 (8.3%) | ||
| Blood bilirubin increased | 3/27 (11.1%) | 10/181 (5.5%) | ||
| Electrocardiogram QT prolonged | 4/27 (14.8%) | 37/181 (20.4%) | ||
| Lipase increased | 9/27 (33.3%) | 10/181 (5.5%) | ||
| Lymphocyte count decreased | 3/27 (11.1%) | 0/181 (0%) | ||
| Weight decreased | 6/27 (22.2%) | 20/181 (11%) | ||
| Alanine aminotransferase increased | 0/27 (0%) | 15/181 (8.3%) | ||
| Blood alkaline phosphatase increased | 0/27 (0%) | 11/181 (6.1%) | ||
| Blood creatinine increased | 0/27 (0%) | 19/181 (10.5%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 10/27 (37%) | 50/181 (27.6%) | ||
| Dehydration | 2/27 (7.4%) | 0/181 (0%) | ||
| Hyperglycaemia | 2/27 (7.4%) | 0/181 (0%) | ||
| Hypoalbuminaemia | 2/27 (7.4%) | 0/181 (0%) | ||
| Hypokalaemia | 5/27 (18.5%) | 18/181 (9.9%) | ||
| Hyponatraemia | 2/27 (7.4%) | 0/181 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 14/27 (51.9%) | 79/181 (43.6%) | ||
| Back pain | 4/27 (14.8%) | 18/181 (9.9%) | ||
| Muscle spasms | 2/27 (7.4%) | 0/181 (0%) | ||
| Myalgia | 3/27 (11.1%) | 18/181 (9.9%) | ||
| Pain in extremity | 2/27 (7.4%) | 13/181 (7.2%) | ||
| Musculoskeletal pain | 0/27 (0%) | 14/181 (7.7%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Acrochordon | 2/27 (7.4%) | 0/181 (0%) | ||
| Melanocytic naevus | 4/27 (14.8%) | 41/181 (22.7%) | ||
| Seborrhoeic keratosis | 3/27 (11.1%) | 36/181 (19.9%) | ||
| Skin papilloma | 7/27 (25.9%) | 50/181 (27.6%) | ||
| Papilloma | 0/27 (0%) | 17/181 (9.4%) | ||
| Nervous system disorders | ||||
| Headache | 4/27 (14.8%) | 26/181 (14.4%) | ||
| Dysgeusia | 0/27 (0%) | 24/181 (13.3%) | ||
| Peripheral sensory neuropathy | 0/27 (0%) | 27/181 (14.9%) | ||
| Psychiatric disorders | ||||
| Anxiety | 2/27 (7.4%) | 14/181 (7.7%) | ||
| Depression | 3/27 (11.1%) | 10/181 (5.5%) | ||
| Insomnia | 0/27 (0%) | 18/181 (9.9%) | ||
| Renal and urinary disorders | ||||
| Haematuria | 2/27 (7.4%) | 0/181 (0%) | ||
| Micturition urgency | 2/27 (7.4%) | 0/181 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 2/27 (7.4%) | 31/181 (17.1%) | ||
| Dysphonia | 2/27 (7.4%) | 0/181 (0%) | ||
| Dyspnoea | 5/27 (18.5%) | 22/181 (12.2%) | ||
| Nasal congestion | 0/27 (0%) | 10/181 (5.5%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Actinic keratosis | 4/27 (14.8%) | 28/181 (15.5%) | ||
| Alopecia | 2/27 (7.4%) | 57/181 (31.5%) | ||
| Dermatitis acneiform | 2/27 (7.4%) | 0/181 (0%) | ||
| Dermatitis bullous | 2/27 (7.4%) | 0/181 (0%) | ||
| Dry skin | 2/27 (7.4%) | 39/181 (21.5%) | ||
| Erythema | 7/27 (25.9%) | 24/181 (13.3%) | ||
| Hyperkeratosis | 4/27 (14.8%) | 58/181 (32%) | ||
| Photosensitivity reaction | 5/27 (18.5%) | 39/181 (21.5%) | ||
| Pruritus | 5/27 (18.5%) | 42/181 (23.2%) | ||
| Rash | 10/27 (37%) | 44/181 (24.3%) | ||
| Rash generalised | 2/27 (7.4%) | 0/181 (0%) | ||
| Rash maculo-papular | 3/27 (11.1%) | 42/181 (23.2%) | ||
| Skin fissures | 2/27 (7.4%) | 0/181 (0%) | ||
| Toxic skin eruption | 2/27 (7.4%) | 0/181 (0%) | ||
| Dermal cyst | 0/27 (0%) | 18/181 (9.9%) | ||
| Dermatitis | 0/27 (0%) | 10/181 (5.5%) | ||
| Keratosis pilaris | 0/27 (0%) | 33/181 (18.2%) | ||
| Milia | 0/27 (0%) | 16/181 (8.8%) | ||
| Palmar-plantar erythrodysaesthesia syndrome | 0/27 (0%) | 48/181 (26.5%) | ||
| Papule | 0/27 (0%) | 13/181 (7.2%) | ||
| Rash papular | 0/27 (0%) | 21/181 (11.6%) | ||
| Skin lesion | 0/27 (0%) | 11/181 (6.1%) | ||
| Vascular disorders | ||||
| Hypertension | 3/27 (11.1%) | 28/181 (15.5%) | ||
Limitations/Caveats
[Not Specified]
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:
NCT01524978
Other Study ID Numbers:
- MO28072
- 2011-004426-10
First Posted:
Feb 2, 2012
Last Update Posted:
Nov 20, 2017
Last Verified:
Oct 1, 2017