Phase II Safety Study of Vemurafenib Followed by Ipilimumab in Subjects With V600 BRAF Mutated Advanced Melanoma
A Single Arm Open-Label Phase II Study of Vemurafenib Followed by Ipilimumab in Subjects With Previously Untreated V600 BRAF Mutated Advanced Melanoma
2 other identifiers
interventional
70
1 country
14
Brief Summary
The purpose of this study is to assess the safety profile of vemurafenib, 960 mg, administered for 6 weeks, followed by ipilimumab monotherapy in patients with BRAF V600 mutated advanced/metastatic melanoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Sep 2012
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 24, 2012
CompletedFirst Posted
Study publicly available on registry
August 28, 2012
CompletedStudy Start
First participant enrolled
September 13, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 25, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
May 12, 2015
CompletedResults Posted
Study results publicly available
October 19, 2015
CompletedJuly 24, 2018
June 1, 2018
1.9 years
August 24, 2012
July 3, 2015
June 26, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Skin Adverse Events (AEs)
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Drug-related=having certain, probable, possible, or unknown relationship to study drug. Grading criteria for AEs: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death.
From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred first
Secondary Outcomes (2)
Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Gastrointestinal Adverse Events (AEs)
From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred first
Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Hepatobiliary Adverse Events
From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred first
Other Outcomes (2)
Number of Participants Who Died, Who Died Due to Related Adverse Events (AEs), and With Related AEs, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to AEs and Related AEs, Immune-related (ir) AEs, and Serious irAEs
From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred first
Number of Participants With Adverse Events (AEs) Grade 3-4, Related AEs Grade 3-4, Related Serious Adverse Events (SAEs) Grade 3-4, Immune-related (ir) AEs Grade 3-4, and Serious irAEs Grade 3-4
From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred first
Study Arms (1)
Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg
EXPERIMENTALParticipants received vemurafenib, 960 mg, twice daily for 6 weeks (Vem1 Phase). After a washout period of 3-10 days, patients received ipilimumab, 10 mg/kg, every 3 weeks for a maximum of 4 doses. At Week 24, participants received ipilimumab, 10 mg/kg, every 12 weeks until disease progression or unacceptable toxicity. Patients who did not progress or have unacceptable toxicity in the Vem1 Phase were retreated with vemurafenib (Vem 2 Phase) at the last dose level identified at the end of the Vem1 Phase until disease progression or unacceptable toxicity.
Interventions
Eligibility Criteria
You may qualify if:
- Men and women 18 years of age and older
- Histologic diagnosis of malignant melanoma tested positive for the BRAF V600 mutation
- Previously untreated unresectable Stage III or Stage IV melanoma
- Complete set of brain/neck, chest, abdomen/pelvis axial radiographs taken within 28 days of first dose of study drug
- Measurable melanoma by physical or radiographic examination
- Brain metastases stable after radiation for at least 1 month and off corticosteroid therapy for ≥30 days prior to enrollment
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Adequate hematologic parameters and renal and hepatic function
You may not qualify if:
- Primary ocular melanoma
- Active brain metastases with symptoms or requiring corticosteroid treatment
- Any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix
- History of or current active autoimmune diseases, including but not limited to inflammatory bowel diseases, rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis, systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies
- History of or current immunodeficiency disease, splenectomy, or splenic irradiation
- Prior anticancer therapy or investigational products \<4 weeks prior to enrollment
- Prior therapy with a BRAF or MEK inhibitor and prior investigational anticancer immunotherapies;
- Prior therapies with immunosuppressive agents within the past 2 years
- Concomitant therapy with any anticancer or potent immunosuppressive agent, surgery, radiotherapy, other investigational anticancer therapies, or chronic use of systemic corticosteroids
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (14)
Beverly Hills Cancer Center
Beverly Hills, California, 90211, United States
Baptist Cancer Institute
Jacksonville, Florida, 32207, United States
Orlando Health, Inc
Orlando, Florida, 32806, United States
Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
University Of New Mexico Cancer Center
Albuquerque, New Mexico, 87106, United States
Mount Sinai School Of Medicine
New York, New York, 10029, United States
Levine Cancer Institute
Charlotte, North Carolina, 28204, United States
Duke University Hospital
Durham, North Carolina, 27710, United States
Dumc
Durham, North Carolina, 27710, United States
University Hospitals Of Cleveland
Cleveland, Ohio, 44106, United States
University Hospitals
Cleveland, Ohio, 44106, United States
Related Publications (1)
Amin A, Lawson DH, Salama AK, Koon HB, Guthrie T Jr, Thomas SS, O'Day SJ, Shaheen MF, Zhang B, Francis S, Hodi FS. Phase II study of vemurafenib followed by ipilimumab in patients with previously untreated BRAF-mutated metastatic melanoma. J Immunother Cancer. 2016 Aug 16;4:44. doi: 10.1186/s40425-016-0148-7. eCollection 2016.
PMID: 27532019DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Bristol-Myers Squibb Study Director
- Organization
- Bristol-Myers Squibb
Study Officials
- STUDY DIRECTOR
Bristol-Myers Squibb
Bristol-Myers Squibb
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 24, 2012
First Posted
August 28, 2012
Study Start
September 13, 2012
Primary Completion
July 25, 2014
Study Completion
May 12, 2015
Last Updated
July 24, 2018
Results First Posted
October 19, 2015
Record last verified: 2018-06