NCT01524978 · CITED IN SOURCE DOCUMENTS

A Study of Vemurafenib in Participants With BRAF V600 Mutation-Positive Cancers

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2017-11-20

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Confirmed Best Overall Response Rate (BORR)

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outcome · POSTED

Percentage of Participants With Confirmed Clinical Benefit

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outcome · POSTED

Overall Response Rate (ORR)

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outcome · POSTED

Duration of Response (DOR)

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outcome · POSTED

Time to Response

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outcome · POSTED

Time to Tumor Progression (TTP)

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outcome · POSTED

Progression Free Survival (PFS)

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Maximum Tolerated Dose for Vemurafenib in Combination With Cetuximab

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outcome · POSTED

Number of Dose-limiting Toxicities of Vemurafenib in Combination With Cetuximab

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outcome · POSTED

Safety: Percentage of Participants With Adverse Event

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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
healthy Volunteers: false
minimum Age: 16 Years
sex: ALL
std Ages: CHILD
ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants with NSCLC will be treated with vemurafenib monotherapy.
intervention Names
Drug: vemurafenib
label
Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - vemurafenib
type
EXPERIMENTAL
description
Participants with ovarian cancer will be treated with vemurafenib monotherapy.
intervention Names
Drug: vemurafenib
label
Cohort 2: Ovarian Cancer - vemurafenib
type
EXPERIMENTAL
description
Participants with colorectal cancer will be treated with vemurafenib monotherapy.
intervention Names
Drug: vemurafenib
label
Cohort 3a: Colorectal Cancer - vemurafenib
type
EXPERIMENTAL
description
Participants with colorectal cancer will be treated with vemurafenib and cetuximab combination therapy.
intervention Names
Drug: cetuximab
Drug: vemurafenib
label
Cohort 3b: Colorectal Cancer - vemurafenib + cetuximab
type
EXPERIMENTAL
description
Participants with cholangiocarcinoma will be treated with vemurafenib monotherapy.
intervention Names
Drug: vemurafenib
label
Cohort 4: Cholangiocarcinoma - vemurafenib
type
EXPERIMENTAL
description
Participants with multiple myeloma will be treated with vemurafenib monotherapy.
intervention Names
Drug: vemurafenib
label
Cohort 6: Multiple Myeloma - vemurafenib
type
EXPERIMENTAL
description
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.
intervention Names
Drug: vemurafenib
label
Cohort 7: Other Solid Tumors - vemurafenib
type
EXPERIMENTAL

interventions

arm Group Labels
Cohort 3b: Colorectal Cancer - vemurafenib + cetuximab
description
Escalating doses administered on Day 1 and then once weekly by intravenous infusion.
name
cetuximab
type
DRUG
arm Group Labels
Cohort 3b: Colorectal Cancer - vemurafenib + cetuximab
description
Escalating doses given orally twice a day starting on Day 2
name
vemurafenib
other Names
Zelboraf
type
DRUG
arm Group Labels
Cohort 1: Non-Small Cell Lung Cancer (NSCLC) - vemurafenib
Cohort 2: Ovarian Cancer - vemurafenib
Cohort 3a: Colorectal Cancer - vemurafenib
Cohort 4: Cholangiocarcinoma - vemurafenib
Cohort 6: Multiple Myeloma - vemurafenib
Cohort 7: Other Solid Tumors - vemurafenib
description
960 mg vemurafenib orally twice a day until disease progression, unacceptable toxicity, or withdrawal of consent.
name
vemurafenib
other Names
Zelboraf
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 208
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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.
measure
Confirmed Best Overall Response Rate (BORR)
time Frame
Up to approximately 3 years

secondary Outcomes

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.
measure
Percentage of Participants With Confirmed Clinical Benefit
time Frame
Up to approximately 3 years
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.
measure
Overall Response Rate (ORR)
time Frame
Up to approximately 3 years
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.
measure
Duration of Response (DOR)
time Frame
Up to approximately 3 years
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.
measure
Time to Response
time Frame
Up to approximately 3 years
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.
measure
Time to Tumor Progression (TTP)
time Frame
Up to approximately 3 years
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.
measure
Progression Free Survival (PFS)
time Frame
Up to approximately 3 years
description
OS was defined as time between the first day of study treatment and date of death of any cause.
measure
Overall Survival (OS)
time Frame
Up to approximately 3 years
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.
measure
Maximum Tolerated Dose for Vemurafenib in Combination With Cetuximab
time Frame
Up to approximately 3 years
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.
measure
Number of Dose-limiting Toxicities of Vemurafenib in Combination With Cetuximab
time Frame
Up to 28 days
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.
measure
Safety: Percentage of Participants With Adverse Event
time Frame
Up to approximately 3 years

Full 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.

Source references

references

citation
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pmid
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citation
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pmid
30351999
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DERIVED
citation
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pmid
26287849
type
DERIVED