Phase II Safety Study of Vemurafenib Followed by Ipilimumab in Subjects With V600 BRAF Mutated Advanced Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01673854
First received: August 24, 2012
Last updated: November 2, 2015
Last verified: November 2015
  Purpose
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.

Condition Intervention Phase
Melanoma
Drug: Ipilimumab
Biological: Vemurafenib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single Arm Open-Label Phase II Study of Vemurafenib Followed by Ipilimumab in Subjects With Previously Untreated V600 BRAF Mutated Advanced Melanoma

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Skin Adverse Events (AEs) [ Time Frame: From last patient's first dose of ipilimumab to 9 weeks ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Gastrointestinal Adverse Events (AEs) [ Time Frame: Week 6 until progressive disease, or unacceptable toxicity (to a maximum of 3 years) ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Particpants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Hepatobiliary Adverse Events [ Time Frame: Week 6 until progressive disease, or unacceptable toxicity (to a maximum of 3 years) ] [ Designated as safety issue: Yes ]
    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.


Other Outcome Measures:
  • 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 [ Time Frame: From first dose of study drug to unacceptable toxicity or progressive disease (to a maximum of 3 years) ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: From first dose of study drug to unacceptable toxicity or progressive disease (to a maximum of 3 years) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 70
Study Start Date: September 2012
Study Completion Date: May 2015
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Yervoy®
  • BMS-734016
Biological: Vemurafenib
Other Name: Zelboraf®

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01673854

Locations
United States, California
Beverly Hills Cancer Center
Beverly Hills, California, United States, 90211
United States, Florida
Baptist Cancer Institute
Jacksonville, Florida, United States, 32207
Orlando Health, Inc
Orlando, Florida, United States, 32806
United States, Georgia
Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, New Mexico
University Of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87106
United States, New York
Mount Sinai School Of Medicine
New York, New York, United States, 10029
United States, North Carolina
Levine Cancer Institute
Charlotte, North Carolina, United States, 28204
Dumc
Durham, North Carolina, United States, 27710
United States, Ohio
University Hospitals Of Cleveland
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01673854     History of Changes
Other Study ID Numbers: CA184-240  2012‐002054‐24 
Study First Received: August 24, 2012
Results First Received: July 3, 2015
Last Updated: November 2, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas

ClinicalTrials.gov processed this record on May 04, 2016