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

August 24, 2012
November 2, 2015
September 2012
July 2014   (final data collection date for primary outcome measure)
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.
Proportion of Ipilimumab treated subjects with Grade 3-4 drug related skin adverse events (AEs) during the sequence of Vemurafenib and Ipilimumab [ Time Frame: 9 weeks after the last subject's first dose (LPFT) of Ipilimumab ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01673854 on ClinicalTrials.gov Archive Site
  • 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.
  • Proportion of Ipilimumab treated subjects with Grade 3-4 drug-related gastrointestinal AEs during the sequence of Vemurafenib and Ipilimumab [ Time Frame: 9 weeks after the last subject's first dose (LPFT) of Ipilimumab ] [ Designated as safety issue: Yes ]
  • Proportion of Ipilimumab treated subjects with Grade 3-4 drug-related hepatobiliary AEs during the sequence of Vemurafenib and Ipilimumab [ Time Frame: 9 weeks after the last subject's first dose (LPFT) of Ipilimumab ] [ Designated as safety issue: Yes ]
  • 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.
Not Provided
 
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.
Not Provided
Interventional
Phase 2
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Melanoma
  • Drug: Ipilimumab
    Other Names:
    • Yervoy®
    • BMS-734016
  • Biological: Vemurafenib
    Other Name: Zelboraf®
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.
Interventions:
  • Drug: Ipilimumab
  • Biological: Vemurafenib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
70
May 2015
July 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01673854
CA184-240, 2012‐002054‐24
No
Not Provided
Not Provided
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP