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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Drug: Ipilimumab; Biological: Vemurafenib

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist Cancer Institute
    • Orlando, Florida, United States, 32806
      • Orlando Health, Inc
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Cancer Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
    • Durham, North Carolina, United States, 27710
      • Duke University Hospital
    • Durham, North Carolina, United States, 27710
      • DUMC
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland
    • Cleveland, Ohio, United States, 44106
      • University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Key Inclusion Criteria:

• 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

Key Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg; Participants 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.

Drug: Ipilimumab; Other Names: BMS-734016; Yervoy®; Biological: Vemurafenib; Other Names: Zelboraf®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Gastrointestinal 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
Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Hepatobiliary Adverse Events	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug.	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	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug. 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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.

Helpful Links

• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2012
• Primary Completion (Actual): July 25, 2014
• Study Completion (Actual): May 12, 2015

Study Registration Dates

• First Submitted: August 24, 2012
• First Submitted That Met QC Criteria: August 24, 2012
• First Posted (Estimate): August 28, 2012

Study Record Updates

• Last Update Posted (Actual): July 24, 2018
• Last Update Submitted That Met QC Criteria: June 26, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Immune Checkpoint Inhibitors; Ipilimumab; Vemurafenib
• Other Study ID Numbers: CA184-240; 2012-002054-24 (EudraCT Number)