search
Back to results

Phase 2 Study of Ipilimumab Plus Dacarbazine in Japanese Patients With Advanced Melanoma

Primary Purpose

Melanoma

Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Ipilimumab
Dacarbazine
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key inclusion criteria:

  • Japanese patients with histologic diagnosis of malignant melanoma
  • Previously untreated Stage III with N3 (unresectable) or Stage IV melanoma
  • Prior adjuvant melanoma therapy permitted
  • Eastern Cooperative Oncology Group performance status of 0 or 1
  • Life expectancy of at least 16 weeks in this study

  • Adequate bone marrow and renal and hepatic function, specifically:

    • white blood cell count ≥2500/uL, absolute neutrophil count ≥1000/uL, platelet count ≥75,000/uL, hemoglobin level ≥9.0 g/dL, creatinine level ≤2.5*upper limit of normal (ULN), aspartate transaminase/alanine transaminase level <2.5*ULN for patients without liver metastasis and <5*ULN for patients with liver metastasis, total bilirubin level <1.5*ULN (for those with Gilbert's Syndrome, lower than 3.0 mg/dL)

Key exclusion criteria:

  • Evidence of brain metastases on brain imaging
  • Active brain metastases with symptoms or requiring corticosteroid treatment; patients with any other malignancy from which they have been disease-free for fewer than 5 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
  • Primary ocular or mucosal melanoma
  • History of or current active autoimmune disease
  • History or concurrent disease of gastrointestinal perforations
  • HIV infection; active Hepatitis B or C or human T-lymphotropic virus type1 infection, based on testing performed during the screening period of this study
  • Prior or concomitant therapy with any anticancer agent for melanoma, or other investigational anticancer therapies
  • Prior adjuvant therapy <4 weeks prior to the start of study drug administration
  • Concomitant therapy with immunosuppressive agents, surgery, or radiotherapy
  • Prior treatment with CTLA-4 inhibitors/agonists or other experimental immunotherapy drugs
  • Treatment with other investigational products within 4 weeks prior to initial treatment of study drug

Sites / Locations

  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2

Arm Description

During the Induction Period, participants received ipilimumab, 10 mg/kg, as tolerated by intravenous (IV) infusion as 1 single dose during Weeks 1 (Day 1), 4, 7, and 10 for a total of 4 separate doses. During the Maintenance Phase, participants received ipilimumab, 10 mg/kg, as tolerated by IV infusion every 12 weeks, beginning at Week 24, until disease progression or unacceptable toxicity occurred or the patient withdrew consent. Participants also received dacarbazine, 850 mg/m^2, by IV infusion over 30 to 60 minutes, starting on Week 1 and repeated every 3 weeks until Week 22. Dacarbazine was dosed on the same day as ipilimumab, when applicable, after the ipilimumab dose.

Outcomes

Primary Outcome Measures

Percentage of Participants Surviving at 1 Year
Survival rate=percentage of participants surviving at 1 year following start of study drug. Every effort was made to collect survival data on all patients, including those withdrawn from treatment for any reason. If the death of a patient was not reported, the patient's last known alive date was recorded. Confidence intervals were computed using the Clopper-Pearson method.

Secondary Outcome Measures

Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs)
irAEs are adverse events of unknown cause, consistent with an immune phenomenon, and considered to be causally related to drug exposure. Six subcategories of irAE are assessed: gastrointestinal, liver, skin, endocrine, neurologic, and other. The irAEs are programmatically determined from a predefined list of MedDRA terms. irAEs will be measured every 3 weeks in induction phase, every 6 weeks in Maintenance Phase to Week 48, and every 12 weeks until Progressive Disease. Grading criteria: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death.
Number of Patients Who Died and Who Had Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, Grade 3-4 AEs, and Related Grade 3-4 AEs
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.

Full Information

First Posted
September 5, 2012
Last Updated
June 9, 2015
Sponsor
Bristol-Myers Squibb
search

1. Study Identification

Unique Protocol Identification Number
NCT01681212
Brief Title
Phase 2 Study of Ipilimumab Plus Dacarbazine in Japanese Patients With Advanced Melanoma
Official Title
Phase 2 Study of Ipilimumab Plus Dacarbazine in Japanese Patients With Previously Untreated Unresectable or Metastatic Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine the survival rate after 1 year of treatment with ipilimumab plus dacarbazine in patients with previously untreated Stage III (unresectable) or Stage IV melanoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ipilimumab, 10 mg/kg + Dacarbazine, 850 mg/m^2
Arm Type
Experimental
Arm Description
During the Induction Period, participants received ipilimumab, 10 mg/kg, as tolerated by intravenous (IV) infusion as 1 single dose during Weeks 1 (Day 1), 4, 7, and 10 for a total of 4 separate doses. During the Maintenance Phase, participants received ipilimumab, 10 mg/kg, as tolerated by IV infusion every 12 weeks, beginning at Week 24, until disease progression or unacceptable toxicity occurred or the patient withdrew consent. Participants also received dacarbazine, 850 mg/m^2, by IV infusion over 30 to 60 minutes, starting on Week 1 and repeated every 3 weeks until Week 22. Dacarbazine was dosed on the same day as ipilimumab, when applicable, after the ipilimumab dose.
Intervention Type
Drug
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
BMS-734016
Intervention Type
Drug
Intervention Name(s)
Dacarbazine
Primary Outcome Measure Information:
Title
Percentage of Participants Surviving at 1 Year
Description
Survival rate=percentage of participants surviving at 1 year following start of study drug. Every effort was made to collect survival data on all patients, including those withdrawn from treatment for any reason. If the death of a patient was not reported, the patient's last known alive date was recorded. Confidence intervals were computed using the Clopper-Pearson method.
Time Frame
At 1 year from start of study drug
Secondary Outcome Measure Information:
Title
Number of Participants With Grade 3-4 Immune-related Adverse Events (irAEs)
Description
irAEs are adverse events of unknown cause, consistent with an immune phenomenon, and considered to be causally related to drug exposure. Six subcategories of irAE are assessed: gastrointestinal, liver, skin, endocrine, neurologic, and other. The irAEs are programmatically determined from a predefined list of MedDRA terms. irAEs will be measured every 3 weeks in induction phase, every 6 weeks in Maintenance Phase to Week 48, and every 12 weeks until Progressive Disease. Grading criteria: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death.
Time Frame
First dose to 90 days following last dose of study drug
Title
Number of Patients Who Died and Who Had Serious Adverse Events (SAEs), Treatment-related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, Grade 3-4 AEs, and Related Grade 3-4 AEs
Description
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.
Time Frame
First dose to 90 days following last dose of study drug. All deaths were poststudy, occurring more than 90 days after the last dose of study drug.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key inclusion criteria: Japanese patients with histologic diagnosis of malignant melanoma Previously untreated Stage III with N3 (unresectable) or Stage IV melanoma Prior adjuvant melanoma therapy permitted Eastern Cooperative Oncology Group performance status of 0 or 1 Life expectancy of at least 16 weeks in this study Adequate bone marrow and renal and hepatic function, specifically: white blood cell count ≥2500/uL, absolute neutrophil count ≥1000/uL, platelet count ≥75,000/uL, hemoglobin level ≥9.0 g/dL, creatinine level ≤2.5*upper limit of normal (ULN), aspartate transaminase/alanine transaminase level <2.5*ULN for patients without liver metastasis and <5*ULN for patients with liver metastasis, total bilirubin level <1.5*ULN (for those with Gilbert's Syndrome, lower than 3.0 mg/dL) Key exclusion criteria: Evidence of brain metastases on brain imaging Active brain metastases with symptoms or requiring corticosteroid treatment; patients with any other malignancy from which they have been disease-free for fewer than 5 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 Primary ocular or mucosal melanoma History of or current active autoimmune disease History or concurrent disease of gastrointestinal perforations HIV infection; active Hepatitis B or C or human T-lymphotropic virus type1 infection, based on testing performed during the screening period of this study Prior or concomitant therapy with any anticancer agent for melanoma, or other investigational anticancer therapies Prior adjuvant therapy <4 weeks prior to the start of study drug administration Concomitant therapy with immunosuppressive agents, surgery, or radiotherapy Prior treatment with CTLA-4 inhibitors/agonists or other experimental immunotherapy drugs Treatment with other investigational products within 4 weeks prior to initial treatment of study drug
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution
City
Fukuoka-shi
State/Province
Fukuoka
ZIP/Postal Code
8128582
Country
Japan
Facility Name
Local Institution
City
Kumamoto-shi
State/Province
Kumamoto
ZIP/Postal Code
8608556
Country
Japan
Facility Name
Local Institution
City
Matsumoto-shi
State/Province
Nagano
ZIP/Postal Code
3908621
Country
Japan
Facility Name
Local Institution
City
Sunto-gun
State/Province
Shizuoka
ZIP/Postal Code
4118777
Country
Japan
Facility Name
Local Institution
City
Chuo-ku
State/Province
Tokyo
ZIP/Postal Code
1040045
Country
Japan
Facility Name
Local Institution
City
Chuo-shi
State/Province
Yamanashi
ZIP/Postal Code
4093898
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
26407818
Citation
Yamazaki N, Uhara H, Fukushima S, Uchi H, Shibagaki N, Kiyohara Y, Tsutsumida A, Namikawa K, Okuyama R, Otsuka Y, Tokudome T. Phase II study of the immune-checkpoint inhibitor ipilimumab plus dacarbazine in Japanese patients with previously untreated, unresectable or metastatic melanoma. Cancer Chemother Pharmacol. 2015 Nov;76(5):969-75. doi: 10.1007/s00280-015-2870-0. Epub 2015 Sep 25.
Results Reference
derived
Links:
URL
http://www.bms.com/studyconnect/Pages/home.aspx
Description
BMS clinical trial educational resource

Learn more about this trial

Phase 2 Study of Ipilimumab Plus Dacarbazine in Japanese Patients With Advanced Melanoma

We'll reach out to this number within 24 hrs