Ph I Ipilimumab Vemurafenib Combo in Patients With v-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF)

This study has been terminated.
(More than 2 of 6 patients treated experienced dose limiting toxicities.)
Sponsor:
Collaborator:
Roche-Genentech
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01400451
First received: July 21, 2011
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

Treatment of subjects who have metastatic melanoma that expresses an activated mutant form of the BRAF oncogene (V600E) with a combination of the specific BRAF inhibitor, Vemurafenib, and the Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) inhibitor mAb Ipilimumab will be safe and feasible and will show preliminary evidence of anti-tumor efficacy and survival in comparison to historical results following treatment with either agent alone.


Condition Intervention Phase
Melanoma
Drug: Ipilimumab (BMS-734016)
Biological: Vemurafenib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Vemurafenib and Ipilimumab in Subjects With V600 BRAF Mutation-positive Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone [ Time Frame: From first vemurafenib dose to day prior to first ipilimumab dose (28 days); Patients who never progressed from Lead-in to combination treatmen (720 mg Alone): first dose to last dose + 90 days, up to Primary Endpoint Data Cut off, approximately 18 months ] [ Designated as safety issue: Yes ]
    AEs graded using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. 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. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling, Gr 5=Death. Related=relationship to study drug reported as certain, probable, possible, or missing. Immune-related AEs (irAEs) characterized by potential association with inflammation and considered by investigator as drug related. Lead In Period: between the first vemurafenib dose and the day prior to the first ipilimumab dose.

  • During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib [ Time Frame: Combination drugs: Day 1 to last dose of drug + 90 days, up to data cut off for Primary Endpoint, approximately 18 months ] [ Designated as safety issue: Yes ]
    AEs graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. 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. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling, Gr 5=Death. Related=relationship to study drug reported as certain, probable, possible, or missing. AEs: onset on or after ipilimumab start and within 90 days of last dose. Immune-related AEs (irAEs) characterized by potential association with inflammation and considered by investigator as drug related. Day 1=first dose of ipilimumab. Data up to data cut off for Primary Endpoint.

  • Number of Participants With Hepatic Dose Limiting Toxicities (DLT) in Participants Treated With Concurrent Ipilimumab and Vemurafenib [ Time Frame: Day 1 to last dose of drug + 90 days up to data cut off for Primary Endpoint, approximately 18 months ] [ Designated as safety issue: Yes ]
    DLT defined as a >= Grade 3 drug-related AE during induction with ipilimumab in combination with vemurafenib excluding:Grade 3 AE of tumor flare (defined as local pain, irritation, or rash localized at sites of known or suspected tumor); Grade 3 cutaneous squamous cell carcinoma; Grade 3 photosensitivity that resolved to a Grade 1 or baseline within 15 days; Grade 3 immune-mediated events of the skin (rash, pruritis) or endocrine systems (hypothyroidism, hyperthyroidism, hypopituitarism, adrenal insufficiency, hypogonadism and cushingoid) that resolved to a Grade 1 or baseline within 28 days; a transient (resolving within 6 hours of onset) Grade 3 infusion-related AE. Hepatic=elevated aspartate aminotransferase and alanine aminotransferase. Maximum tolerable dose (MTD) was defined as the maximum dose of combination treatment that could be given to 6 subjects such that no more than 2 subjects experience DLT. Day 1=first day of concurrent therapy with ipilimumab and vemurafenib.


Enrollment: 18
Study Start Date: November 2011
Study Completion Date: December 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ipilimumab + Vemurafenib Drug: Ipilimumab (BMS-734016)
Injection, intravenous (i.v.), cohort 1: 3 mg/kg, Escalate to cohort 2: 10 mg/kg, Escalate to cohort 3: at Recommended Phase 2 Dose (RP2D), De-escalate cohort 1A: 3 mg/kg, De-escalate cohort -1B: 10 mg/kg, (every three week) Q3wk, upto 2 yrs
Other Names:
  • Yervoy®
  • Ipilimumab
  • BMS-734016
Biological: Vemurafenib
tablets, oral, cohort 1: 960 mg Twice daily (BID) x 28 days after date, cohort 2: 960 mg BID x 28 days after date, cohort 3: at Recommended Phase 2 Dose (RP2D) x 14 days after date, De-escalate cohort 1A: 720 mg BID x 28 days after date, De-escalate cohort -1B: 720 mg BID x 28 days after date , Up to 2 yrs

  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.

Inclusion Criteria:

  • Metastatic melanoma with activating V600 BRAF mutation
  • Measurable Tumor
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1

Exclusion Criteria:

  • Autoimmune disease
  • Active Brain Metastasis (must be stable after radiation for at least one month)
  • Prior therapy with immune stimulating agents
  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: NCT01400451

Locations
United States, California
University Of California Los Angeles
Los Angeles, California, United States, 90095
United States, Massachusetts
Dana Farber Cancer Inst
Boston, Massachusetts, United States, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Bristol-Myers Squibb
Roche-Genentech
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01400451     History of Changes
Other Study ID Numbers: CA184-161 ST, 2011-000906-22
Study First Received: July 21, 2011
Results First Received: April 21, 2014
Last Updated: May 19, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 22, 2014