Evaluation of Tumor Response to Ipilimumab in the Treatment of Melanoma With Brain Metastases
Study Details
Study Description
Brief Summary
To assess the response of melanoma with brain metastases to ipilimumab treatment while maintaining acceptable tolerability.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ipilimumab, 10 mg/kg, IV in corticosteroid-free patients Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV, every 12 weeks, beginning at Week 24. |
Drug: Ipilimumab
10 mg/kg, administered as an intravenous infusion every 3 weeks during induction and every 12 weeks during maintenance
Other Names:
|
| Experimental: Ipilimumab, 10 mg/kg, IV in corticosteroid-dependent patients Participants who were dependent on corticosteroid therapy received ipilimumab, 10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV, every 12 weeks, beginning at Week 24. |
Drug: Ipilimumab
10 mg/kg, administered as an intravenous infusion every 3 weeks during induction and every 12 weeks during maintenance
Other Names:
Drug: Corticosteroid: Betamethasone
Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with betamethasone
Drug: Corticosteroid: Dexamethasone
Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with dexamethasone
Drug: Corticosteroid: Fludrocortisone
Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with fludrocortisone
Drug: Corticosteroid: Hydrocortisone
Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with hydrocortisone
Drug: Corticosteroid: Meprednisone
Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with meprednisone
Drug: Corticosteroid: Methylprednisolone
Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with methylprednisolone
Drug: Corticosteroid: Prednisolone
Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with prednisolone
Drug: Corticosteroid: Prednisone
Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with prednisone
Drug: Corticosteroid: Triamcinolone
Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with triamcinolone
|
Outcome Measures
Primary Outcome Measures
- Disease Control Rate by Modified World Health Organization (mWHO) Tumor Assessment Criteria [From Day 1, first dose to end of Week 12]
Disease control rate is defined as the number of patients with a best overall response of complete response (CR), partial response (PR), or stable disease (SD) (global, in brain, or outside of brain) based on mWHO criteria divided by the number of patients who received treatment. By mWHO criteria: CR=complete disappearance of all index lesions. PR=decrease, relative to baseline, of 50% or greater in the sum of the 2 largest perpendicular diameters of all index lesions. SD=does not meet criteria for CR or PR, in the absence of progressive disease (PD). Patients with PR or CR not confirmed after at least 4 weeks are scored as SD unless they have new primary lesions. PD=at least 25% increase in the sum of the diameters of all index lesions (taking as reference the smallest sum recorded at or following baseline) and/or the appearance of any new lesions. CNS=central nervous system.
Secondary Outcome Measures
- Disease Control Rate by Immune-related Response Criteria (irRC) [From Day 1, first dose to end of Week 12]
Disease control rate is defined as the number of patients with a best overall response of immune-related (ir) complete response (irCR), partial response (irPR), or stable disease (irSD) divided by the total number of patients who received treatment. By irRC definition: irCR=complete disappearance of all index lesions. irPR=decrease, relative to baseline, of 50% or greater in the sum of the products of the 2 largest perpendicular diameters of all index lesions. irSD=does not meet criteria for irCR or irPR, in the absence of ir progressive disease (irPD). irPD=at least 25% increase in the sum of the products of all index lesions (taking as reference the smallest sum recorded at or following baseline). CNS=central nervous system; non-CNS compartment=extracranial, or outside of the brain.
- Best Overall Response Rate (BORR) by Modified World Health Organization (mWHO) Criteria and by Immune-relate Response Criteria (irRC) [From Day 1, first dose until the last tumor assessment, Week 12]
BORR is defined as the number of patients whose global best overall response (BOR) was complete (CR) or partial response (PR), divided by the total number of participants who received treatment. CR=complete disappearance of all index lesions. PR=decrease, relative to baseline, of 50% or greater in the sum of the products of the 2 largest perpendicular diameters of all index lesions. The global BOR is the best overall response (OR) designation over the study as a whole for an individual in the study based on overall tumor burden. Both central nervous system (CNS) (brain lesions) and non-CNS compartments (lesions outside the brain) are considered for the global BOR. For the analysis of global BOR of CR or PR (by both modified WHO criteria and immune-related response criteria [irRC]), the OR assessment must be confirmed by a second (confirmatory) evaluation meeting the criteria for response and must be performed no less than 4 weeks after the criteria for response are first met.
- Duration of Response (DOR) by Modified World Health Organization (mWHO) Criteria and by Immune-related Response Criteria (irRC) [From Day 1, first dose to last tumor assessment up to 18.2 months]
DOR is defined in patients whose global best overall response is complete (CR) or partial response (PR) as the time between the date of response of confirmed CR or PR, whichever occurs first, and the date of progressive disease or death, whichever occurs first. For patients who remain alive and have not progressed following response, duration of response will be censored on the date of last evaluable tumor assessment.
- Progression-free Survival (PFS) by Modified World Health Organization (mWHO) Criteria and by Immune-related Response Criteria (irRC) [From Day 1, first dose to the date of progression or death, whichever occurred first up to 22 months]
PFS is defined as the time between the date of the first dose of study therapy and the date of progression or death, whichever occurs first. A patient who dies without reported prior progression will be considered to have progressed on the date of death. For those who remain alive and have not progressed, PFS will be censored on the date of last evaluable tumor assessment. Participants who have not died and have no recorded postbaseline tumor assessment will be censored on the date of first dose of study therapy. Those who die without any recorded postbaseline tumor assessment will be considered to have progressed on the date of death.
- Number of Participants Surviving at 6, 12, 18, 24, and 36 Months (Overall Survival [OS] Rate) [From first dose to Months 6, 12, 18, 24, and 36 months]
OS is defined as the time from the first dose of study drug until the date of death. Overall survival rate is the percentage of participants known to be alive at a timepoint. For those patients who did not die, OS was censored at the recorded last date of patient contact, and those with a missing recorded last date of contact will be censored at the last date the patient was known to be alive. The survival rate at a specified time-point is the probability that a patient is alive at that time following randomization. The rate is calculated for each treatment group using the Kaplan-Meier product-limit method. A corresponding 2-sided 95% bootstrap confidence interval will be calculated.
- Number of Participants Who Died or Had a Treatment-related Adverse Event (AE), Immune-related AE, Immune-related Serious Adverse Event (SAE), Nervous System Disorder, Treatment-related Nervous System Disorder, SAE, and AE Leading to Discontinuation [Continuously from Day 1, first dose, to 70 days following last dose of ipilimumab]
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. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
- Onset of Response by Modified World Health Organization (mWHO) Criteria and Immune-related Response Criteria (irRC) [From Day 1, first dose to a maximum of 4.2 months]
Onset of response is defined as the time between the first dose of study therapy and the date when measurement criteria are first met for global best overall response of partial (PR) or complete (CR), whichever occurs first. CR=complete disappearance of all index lesions. PR=decrease, relative to baseline, of 50% or greater in the sum of the 2 largest perpendicular diameters of all index lesions.
- Overall Survival (OS) [From first dose to 24 months]
OS is defined as the time from date of first dose of study drug until the date of death. For those patients who did not die, OS was censored at the recorded last date of patient contact, and those missing a recorded last date of contact will be censored at the last date the patient was known to be alive.
Eligibility Criteria
Criteria
Key inclusion criteria
-
Histologically confirmed malignant melanoma
-
At least 1 measurable index brain metastasis >0.5 cm and no larger than 3 cm in diameter that had not been previously irradiated, and/or 2 measurable lesions >0.3 cm visible on contrast magnetic resonance
-
Index brain lesion must have resolved consequences of prior therapy that could have confounded attribution of tumor response including edema and hemorrhage
-
Participants in ipilimumab monotherapy arm (including the first 21 who were enrolled in Stage 1) were to be free of neurologic symptoms related to metastatic brain lesions and must not have required or received systemic corticosteroid therapy in the 10 days prior to beginning ipilimumab therapy
-
Eastern Cooperative Oncology Group performance status of 0 or 1
-
Required values for initial laboratory tests:
-
White blood cell count ≥2000/μL
-
Absolute neutrophil count ≥1000/μL
-
Platelets ≥100*10^3/μL
-
Hemoglobin level ≥9 g/dL (may have been transfused)
-
Aspartate aminotransferase/alanine aminotransferase (AST/ALT) level ≤2.5*ULN for participants without liver metastasis
-
AST/ALT level ≤5*ULN for those with liver metastasis
-
Bilirubin level ≤2*ULN (except participants with Gilbert's Syndrome, who must have had a total bilirubin level less than 3.0 mg/dL)
-
Age 16 years and older
-
Males and females
-
Women of childbearing potential (WOBP) must be using an adequate method of contraception to avoid pregnancy throughout the study (and for up to 26 weeks after the last dose of investigational product) in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal.
Key exclusion criteria
-
History of carcinomatous meningitis, with prior stereotactic or highly conformal radiotherapy and/or whole brain irradiation within 14 days before the first dose of ipilimumab, and documented history of autoimmune disease
-
Prior stereotactic or highly conformal radiotherapy and/or whole brain irradiation within 14 days prior to start of ipilimumab dosing for this study. Note the stereotactic radiotherapy field must not have included the brain index lesion or the lesion must have been detected and confirmed to be active and progressing after receiving whole brain irradiation.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic Arizona | Scottsdale | Arizona | United States | 85259 |
| 2 | City Of Hope | Duarte | California | United States | 91010-3000 |
| 3 | The Angeles Clinic & Research Institute | Los Angeles | California | United States | 90025 |
| 4 | Yale University School Of Medicine | New Haven | Connecticut | United States | 06520 |
| 5 | Loyola University Medical Center | Maywood | Illinois | United States | 60153 |
| 6 | Oncology Specialists, S.C. | Park Ridge | Illinois | United States | 60068 |
| 7 | Indiana University Cancer Center | Indianapolis | Indiana | United States | 46202 |
| 8 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 9 | Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756 |
| 10 | Local Institution | Bronx | New York | United States | 10466 |
| 11 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 12 | Providence Portland Med Ctr | Portland | Oregon | United States | 97213 |
| 13 | Vanderbilt-Ingram Cancer Ctr | Nashville | Tennessee | United States | 37232 |
| 14 | Seattle Cancer Care Alliance | Seattle | Washington | United States | 98109-1023 |
Sponsors and Collaborators
- Bristol-Myers Squibb
- Medarex
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- CA184-042
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | A total of 99 participants were enrolled, and 27 did not receive treatment because they did not meet screening criteria. |
| Arm/Group Title | Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients | Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients |
|---|---|---|
| Arm/Group Description | Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. | Participants who required concurrent systemic corticosteroid therapy for adequate control of neurologic signs and symptoms related to metastatic brain lesion received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. |
| Period Title: Induction Phase (Day 1 to Week 24) | ||
| STARTED | 51 | 21 |
| COMPLETED | 15 | 5 |
| NOT COMPLETED | 36 | 16 |
| Period Title: Induction Phase (Day 1 to Week 24) | ||
| STARTED | 11 | 2 |
| COMPLETED | 1 | 0 |
| NOT COMPLETED | 10 | 2 |
Baseline Characteristics
| Arm/Group Title | Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients | Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients | Total |
|---|---|---|---|
| Arm/Group Description | Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. | Participants who were dependent on corticosteroid therapy received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. | Total of all reporting groups |
| Overall Participants | 51 | 21 | 72 |
| Age, Customized (Number) [Number] | |||
| Younger than 65 years |
39
76.5%
|
17
81%
|
56
77.8%
|
| 65 years and older |
12
23.5%
|
4
19%
|
16
22.2%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
18
35.3%
|
10
47.6%
|
28
38.9%
|
| Male |
33
64.7%
|
11
52.4%
|
44
61.1%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
51
100%
|
21
100%
|
72
100%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Eastern Cooperative Oncology Group (ECOG) score (Units on a scale) [Number] | |||
| 0 |
25
|
14
|
39
|
| 1 |
26
|
7
|
33
|
Outcome Measures
| Title | Disease Control Rate by Modified World Health Organization (mWHO) Tumor Assessment Criteria |
|---|---|
| Description | Disease control rate is defined as the number of patients with a best overall response of complete response (CR), partial response (PR), or stable disease (SD) (global, in brain, or outside of brain) based on mWHO criteria divided by the number of patients who received treatment. By mWHO criteria: CR=complete disappearance of all index lesions. PR=decrease, relative to baseline, of 50% or greater in the sum of the 2 largest perpendicular diameters of all index lesions. SD=does not meet criteria for CR or PR, in the absence of progressive disease (PD). Patients with PR or CR not confirmed after at least 4 weeks are scored as SD unless they have new primary lesions. PD=at least 25% increase in the sum of the diameters of all index lesions (taking as reference the smallest sum recorded at or following baseline) and/or the appearance of any new lesions. CNS=central nervous system. |
| Time Frame | From Day 1, first dose to end of Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of ipilimumab |
| Arm/Group Title | Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients | Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients |
|---|---|---|
| Arm/Group Description | Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. | Participants who required concurrent systemic corticosteroid therapy for adequate control of neurologic signs and symptoms related to metastatic brain lesion received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. |
| Measure Participants | 51 | 21 |
| Global disease control rate |
17.6
34.5%
|
4.8
22.9%
|
| Disease control rate in brain |
23.5
46.1%
|
9.5
45.2%
|
| Title | Disease Control Rate by Immune-related Response Criteria (irRC) |
|---|---|
| Description | Disease control rate is defined as the number of patients with a best overall response of immune-related (ir) complete response (irCR), partial response (irPR), or stable disease (irSD) divided by the total number of patients who received treatment. By irRC definition: irCR=complete disappearance of all index lesions. irPR=decrease, relative to baseline, of 50% or greater in the sum of the products of the 2 largest perpendicular diameters of all index lesions. irSD=does not meet criteria for irCR or irPR, in the absence of ir progressive disease (irPD). irPD=at least 25% increase in the sum of the products of all index lesions (taking as reference the smallest sum recorded at or following baseline). CNS=central nervous system; non-CNS compartment=extracranial, or outside of the brain. |
| Time Frame | From Day 1, first dose to end of Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of ipilimumab |
| Arm/Group Title | Ipilimumab 10 mg/kg IV, in Corticosteroid-free Patients | Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients |
|---|---|---|
| Arm/Group Description | Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. | Participants who required concurrent systemic corticosteroid therapy for adequate control of neurologic signs and symptoms related to metastatic brain lesion received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. |
| Measure Participants | 51 | 21 |
| Global disease control rate |
25.5
50%
|
9.5
45.2%
|
| Disease control rate in brain lesions |
25.5
50%
|
9.5
45.2%
|
| Disease control rate in non-CNS compartment |
33.3
65.3%
|
9.5
45.2%
|
| Title | Best Overall Response Rate (BORR) by Modified World Health Organization (mWHO) Criteria and by Immune-relate Response Criteria (irRC) |
|---|---|
| Description | BORR is defined as the number of patients whose global best overall response (BOR) was complete (CR) or partial response (PR), divided by the total number of participants who received treatment. CR=complete disappearance of all index lesions. PR=decrease, relative to baseline, of 50% or greater in the sum of the products of the 2 largest perpendicular diameters of all index lesions. The global BOR is the best overall response (OR) designation over the study as a whole for an individual in the study based on overall tumor burden. Both central nervous system (CNS) (brain lesions) and non-CNS compartments (lesions outside the brain) are considered for the global BOR. For the analysis of global BOR of CR or PR (by both modified WHO criteria and immune-related response criteria [irRC]), the OR assessment must be confirmed by a second (confirmatory) evaluation meeting the criteria for response and must be performed no less than 4 weeks after the criteria for response are first met. |
| Time Frame | From Day 1, first dose until the last tumor assessment, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of ipilimumab |
| Arm/Group Title | Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients | Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients |
|---|---|---|
| Arm/Group Description | Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. | Participants who required concurrent systemic corticosteroid therapy for adequate control of neurologic signs and symptoms related to metastatic brain lesion received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. |
| Measure Participants | 51 | 21 |
| Global BORR (mWHO criteria) |
9.8
19.2%
|
4.8
22.9%
|
| BORR in brain (mWHO criteria) |
15.7
30.8%
|
4.8
22.9%
|
| BORR in non-CNS compartment (mWHO criteria) |
13.7
26.9%
|
4.8
22.9%
|
| Global BORR (irRC) |
9.8
19.2%
|
4.8
22.9%
|
| BORR in brain (irRC) |
15.7
30.8%
|
4.8
22.9%
|
| BORR in non-CNS compartment (irRC criteria ) |
13.7
26.9%
|
4.8
22.9%
|
| Title | Duration of Response (DOR) by Modified World Health Organization (mWHO) Criteria and by Immune-related Response Criteria (irRC) |
|---|---|
| Description | DOR is defined in patients whose global best overall response is complete (CR) or partial response (PR) as the time between the date of response of confirmed CR or PR, whichever occurs first, and the date of progressive disease or death, whichever occurs first. For patients who remain alive and have not progressed following response, duration of response will be censored on the date of last evaluable tumor assessment. |
| Time Frame | From Day 1, first dose to last tumor assessment up to 18.2 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of ipilimumab |
| Arm/Group Title | Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients | Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients |
|---|---|---|
| Arm/Group Description | Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. | Participants who were dependent on corticosteroid therapy received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. |
| Measure Participants | 51 | 21 |
| DOR by mWHO criteria |
10.4
|
NA
|
| DOR by irRC |
10.4
|
NA
|
| Title | Progression-free Survival (PFS) by Modified World Health Organization (mWHO) Criteria and by Immune-related Response Criteria (irRC) |
|---|---|
| Description | PFS is defined as the time between the date of the first dose of study therapy and the date of progression or death, whichever occurs first. A patient who dies without reported prior progression will be considered to have progressed on the date of death. For those who remain alive and have not progressed, PFS will be censored on the date of last evaluable tumor assessment. Participants who have not died and have no recorded postbaseline tumor assessment will be censored on the date of first dose of study therapy. Those who die without any recorded postbaseline tumor assessment will be considered to have progressed on the date of death. |
| Time Frame | From Day 1, first dose to the date of progression or death, whichever occurred first up to 22 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of ipilimumab |
| Arm/Group Title | Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients | Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients |
|---|---|---|
| Arm/Group Description | Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. | Participants who required concurrent systemic corticosteroid therapy for adequate control of neurologic signs and symptoms related to metastatic brain lesion received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. |
| Measure Participants | 51 | 21 |
| Global PFS (mWHO criteria) |
1.4
|
1.2
|
| PFS in brain (mWHO criteria) |
1.5
|
1.2
|
| PFS in non-CNS compartment (mWHO criteria) |
2.6
|
1.3
|
| Global PFS (irRC) |
2.7
|
1.3
|
| PFS in brain (irRC) |
1.9
|
1.2
|
| PFS in non-CNS compartment (irRC) |
3.3
|
1.3
|
| Title | Number of Participants Surviving at 6, 12, 18, 24, and 36 Months (Overall Survival [OS] Rate) |
|---|---|
| Description | OS is defined as the time from the first dose of study drug until the date of death. Overall survival rate is the percentage of participants known to be alive at a timepoint. For those patients who did not die, OS was censored at the recorded last date of patient contact, and those with a missing recorded last date of contact will be censored at the last date the patient was known to be alive. The survival rate at a specified time-point is the probability that a patient is alive at that time following randomization. The rate is calculated for each treatment group using the Kaplan-Meier product-limit method. A corresponding 2-sided 95% bootstrap confidence interval will be calculated. |
| Time Frame | From first dose to Months 6, 12, 18, 24, and 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of ipilimumab |
| Arm/Group Title | Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients | Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients |
|---|---|---|
| Arm/Group Description | Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. | Participants who required concurrent systemic corticosteroid therapy for adequate control of neurologic signs and symptoms related to metastatic brain lesion received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. |
| Measure Participants | 51 | 21 |
| At 6 months |
0.55
|
0.38
|
| At 12 months |
0.31
|
0.19
|
| At 18 months |
0.26
|
0.19
|
| At 24 months |
0.26
|
0.10
|
| At 36 months |
0.26
|
0.10
|
| Title | Number of Participants Who Died or Had a Treatment-related Adverse Event (AE), Immune-related AE, Immune-related Serious Adverse Event (SAE), Nervous System Disorder, Treatment-related Nervous System Disorder, SAE, and AE Leading to Discontinuation |
|---|---|
| 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. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. |
| Time Frame | Continuously from Day 1, first dose, to 70 days following last dose of ipilimumab |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of ipilimumab |
| Arm/Group Title | Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients | Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients |
|---|---|---|
| Arm/Group Description | Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. | Participants who were dependent on corticosteroid therapy received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. |
| Measure Participants | 51 | 21 |
| Deaths |
37
72.5%
|
20
95.2%
|
| Treatment-related AEs (all) |
45
88.2%
|
17
81%
|
| Treatment-related AEs (Grade 3/4) |
17
33.3%
|
4
19%
|
| Treatment-related AEs (Fatal) |
0
0%
|
0
0%
|
| Immune-related AEs (All) |
35
68.6%
|
13
61.9%
|
| Immune-related AEs (Grade 3/4) |
11
21.6%
|
3
14.3%
|
| Immune-related AEs (Fatal) |
0
0%
|
0
0%
|
| Immune-related SAEs (All) |
11
21.6%
|
6
28.6%
|
| Immune-related SAES (Grade 3/4) |
7
13.7%
|
3
14.3%
|
| Immune-related SAES (Fatal) |
0
0%
|
0
0%
|
| Nervous system disorder (NSD) (All) |
40
78.4%
|
14
66.7%
|
| NSD (Grade 3/4) |
17
33.3%
|
7
33.3%
|
| NSD (Fatal) |
0
0%
|
1
4.8%
|
| Treatment-related NSD (All) |
8
15.7%
|
3
14.3%
|
| Treatment-related NSD (Gr 3/4) |
1
2%
|
0
0%
|
| Treatment-related NSD (Fatal) |
0
0%
|
0
0%
|
| SAE (All) |
36
70.6%
|
17
81%
|
| SAE (Grade 3/4) |
18
35.3%
|
7
33.3%
|
| SAE (Fatal) |
17
33.3%
|
10
47.6%
|
| AEs leading to discontinuation (All) |
15
29.4%
|
9
42.9%
|
| AEs leading to discontinuation (Grade 3/4) |
9
17.6%
|
4
19%
|
| AEs leading to discontinuation (Fatal) |
5
9.8%
|
4
19%
|
| Title | Onset of Response by Modified World Health Organization (mWHO) Criteria and Immune-related Response Criteria (irRC) |
|---|---|
| Description | Onset of response is defined as the time between the first dose of study therapy and the date when measurement criteria are first met for global best overall response of partial (PR) or complete (CR), whichever occurs first. CR=complete disappearance of all index lesions. PR=decrease, relative to baseline, of 50% or greater in the sum of the 2 largest perpendicular diameters of all index lesions. |
| Time Frame | From Day 1, first dose to a maximum of 4.2 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of ipilimumab. n=number of participants with a best overall response of CR or PR. |
| Arm/Group Title | Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients | Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients |
|---|---|---|
| Arm/Group Description | Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. | Participants who were dependent on corticosteroid therapy received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. |
| Measure Participants | 51 | 21 |
| Onset of response (mWHO criteria) (n=5, 1) |
1.2
|
1.2
|
| Onset of response (irRC) (n=5, 1) |
1.2
|
1.2
|
| Title | Overall Survival (OS) |
|---|---|
| Description | OS is defined as the time from date of first dose of study drug until the date of death. For those patients who did not die, OS was censored at the recorded last date of patient contact, and those missing a recorded last date of contact will be censored at the last date the patient was known to be alive. |
| Time Frame | From first dose to 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of ipilimumab |
| Arm/Group Title | Ipilimumab, 10 mg/kg, IV in Corticosteroid-free Patients | Ipilimumab, 10 mg/kg, IV in Corticosteroid-dependent Patients |
|---|---|---|
| Arm/Group Description | Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV, every 12 weeks, beginning at Week 24. Ipilimumab: 10 mg/kg, administered as an intravenous infusion every 3 weeks during induction and every 12 weeks during maintenance | Participants who required concurrent systemic corticosteroid therapy for adequate control of neurologic signs and symptoms related to metastatic brain lesion received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. |
| Measure Participants | 51 | 21 |
| Median (95% Confidence Interval) [Months] |
6.97
|
3.75
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients | Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients | ||
| Arm/Group Description | Participants who required concurrent systemic corticosteroid therapy for adequate control of neurologic signs and symptoms related to metastatic brain lesion received ipilimumab,10 mg/kg, as a 90-minute IV infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. | Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV every 12 weeks, beginning at Week 24. | ||
All Cause Mortality |
||||
| Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients | Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients | Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/21 (81%) | 36/51 (70.6%) | ||
| Blood and lymphatic system disorders | ||||
| Thrombocytopenia | 0/21 (0%) | 1/51 (2%) | ||
| Cardiac disorders | ||||
| Bradycardia | 0/21 (0%) | 1/51 (2%) | ||
| Atrial fibrillation | 0/21 (0%) | 1/51 (2%) | ||
| Endocrine disorders | ||||
| Adrenal insufficiency | 1/21 (4.8%) | 2/51 (3.9%) | ||
| Hypophysitis | 0/21 (0%) | 1/51 (2%) | ||
| Eye disorders | ||||
| Conjunctivitis | 0/21 (0%) | 2/51 (3.9%) | ||
| Retinal detachment | 0/21 (0%) | 1/51 (2%) | ||
| Gastrointestinal disorders | ||||
| Intestinal ischaemia | 0/21 (0%) | 1/51 (2%) | ||
| Ascites | 0/21 (0%) | 1/51 (2%) | ||
| Diarrhoea | 2/21 (9.5%) | 6/51 (11.8%) | ||
| Pancreatitis | 0/21 (0%) | 1/51 (2%) | ||
| Abdominal pain | 0/21 (0%) | 2/51 (3.9%) | ||
| Haematochezia | 1/21 (4.8%) | 0/51 (0%) | ||
| Small intestinal obstruction | 0/21 (0%) | 1/51 (2%) | ||
| Vomiting | 0/21 (0%) | 5/51 (9.8%) | ||
| Colitis | 3/21 (14.3%) | 5/51 (9.8%) | ||
| Nausea | 0/21 (0%) | 5/51 (9.8%) | ||
| Peritoneal haemorrhage | 1/21 (4.8%) | 0/51 (0%) | ||
| General disorders | ||||
| Fatigue | 1/21 (4.8%) | 2/51 (3.9%) | ||
| Pyrexia | 0/21 (0%) | 3/51 (5.9%) | ||
| Disease progression | 10/21 (47.6%) | 16/51 (31.4%) | ||
| Pain | 0/21 (0%) | 1/51 (2%) | ||
| Hepatobiliary disorders | ||||
| Bile duct stone | 0/21 (0%) | 1/51 (2%) | ||
| Hyperbilirubinaemia | 0/21 (0%) | 1/51 (2%) | ||
| Immune system disorders | ||||
| Hypersensitivity | 1/21 (4.8%) | 0/51 (0%) | ||
| Infections and infestations | ||||
| Pneumonia | 0/21 (0%) | 3/51 (5.9%) | ||
| Pneumonia viral | 0/21 (0%) | 1/51 (2%) | ||
| Sepsis | 1/21 (4.8%) | 1/51 (2%) | ||
| Metapneumovirus infection | 0/21 (0%) | 1/51 (2%) | ||
| Colon gangrene | 0/21 (0%) | 1/51 (2%) | ||
| Septic shock | 0/21 (0%) | 1/51 (2%) | ||
| Bacteraemia | 1/21 (4.8%) | 0/51 (0%) | ||
| Urinary tract infection | 0/21 (0%) | 1/51 (2%) | ||
| Injury, poisoning and procedural complications | ||||
| Fracture | 1/21 (4.8%) | 0/51 (0%) | ||
| Brain herniation | 0/21 (0%) | 1/51 (2%) | ||
| Investigations | ||||
| Lipase increased | 0/21 (0%) | 1/51 (2%) | ||
| Aspartate aminotransferase increased | 1/21 (4.8%) | 0/51 (0%) | ||
| Alanine aminotransferase increased | 1/21 (4.8%) | 1/51 (2%) | ||
| Metabolism and nutrition disorders | ||||
| Hyponatraemia | 1/21 (4.8%) | 0/51 (0%) | ||
| Decreased appetite | 0/21 (0%) | 1/51 (2%) | ||
| Dehydration | 2/21 (9.5%) | 5/51 (9.8%) | ||
| Hyperglycaemia | 0/21 (0%) | 1/51 (2%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 1/21 (4.8%) | 0/51 (0%) | ||
| Muscular weakness | 1/21 (4.8%) | 1/51 (2%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Tumour pain | 0/21 (0%) | 1/51 (2%) | ||
| Metastatic malignant melanoma | 0/21 (0%) | 1/51 (2%) | ||
| Nervous system disorders | ||||
| Ataxia | 1/21 (4.8%) | 0/51 (0%) | ||
| Cerebral haemorrhage | 1/21 (4.8%) | 3/51 (5.9%) | ||
| Syncope | 1/21 (4.8%) | 0/51 (0%) | ||
| Cerebrovascular accident | 0/21 (0%) | 1/51 (2%) | ||
| Hemiparesis | 2/21 (9.5%) | 0/51 (0%) | ||
| Mental impairment | 1/21 (4.8%) | 0/51 (0%) | ||
| Somnolence | 0/21 (0%) | 3/51 (5.9%) | ||
| Lethargy | 0/21 (0%) | 1/51 (2%) | ||
| Loss of consciousness | 0/21 (0%) | 1/51 (2%) | ||
| Headache | 0/21 (0%) | 2/51 (3.9%) | ||
| Aphasia | 1/21 (4.8%) | 0/51 (0%) | ||
| Peripheral sensory neuropathy | 0/21 (0%) | 1/51 (2%) | ||
| Depressed level of consciousness | 2/21 (9.5%) | 2/51 (3.9%) | ||
| Speech disorder | 0/21 (0%) | 1/51 (2%) | ||
| Haemorrhage intracranial | 1/21 (4.8%) | 0/51 (0%) | ||
| Convulsion | 3/21 (14.3%) | 3/51 (5.9%) | ||
| Peripheral motor neuropathy | 1/21 (4.8%) | 0/51 (0%) | ||
| Psychiatric disorders | ||||
| Confusional state | 2/21 (9.5%) | 5/51 (9.8%) | ||
| Mental status changes | 0/21 (0%) | 2/51 (3.9%) | ||
| Renal and urinary disorders | ||||
| Renal failure acute | 0/21 (0%) | 1/51 (2%) | ||
| Renal failure | 1/21 (4.8%) | 0/51 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Lung infiltration | 0/21 (0%) | 1/51 (2%) | ||
| Pulmonary embolism | 0/21 (0%) | 2/51 (3.9%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 1/21 (4.8%) | 0/51 (0%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 0/21 (0%) | 1/51 (2%) | ||
| Hypotension | 1/21 (4.8%) | 0/51 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Ipilimumab, 10 mg/kg IV, in Corticosteroid-dependent Patients | Ipilimumab, 10 mg/kg IV, in Corticosteroid-free Patients | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 20/21 (95.2%) | 48/51 (94.1%) | ||
| Cardiac disorders | ||||
| Sinus tachycardia | 2/21 (9.5%) | 0/51 (0%) | ||
| Endocrine disorders | ||||
| Adrenal insufficiency | 2/21 (9.5%) | 1/51 (2%) | ||
| Eye disorders | ||||
| Visual impairment | 2/21 (9.5%) | 1/51 (2%) | ||
| Vision blurred | 2/21 (9.5%) | 7/51 (13.7%) | ||
| Gastrointestinal disorders | ||||
| Stomatitis | 2/21 (9.5%) | 0/51 (0%) | ||
| Dyspepsia | 2/21 (9.5%) | 6/51 (11.8%) | ||
| Constipation | 5/21 (23.8%) | 9/51 (17.6%) | ||
| Diarrhoea | 9/21 (42.9%) | 24/51 (47.1%) | ||
| Abdominal pain | 3/21 (14.3%) | 4/51 (7.8%) | ||
| Vomiting | 1/21 (4.8%) | 10/51 (19.6%) | ||
| Flatulence | 2/21 (9.5%) | 4/51 (7.8%) | ||
| Nausea | 4/21 (19%) | 19/51 (37.3%) | ||
| General disorders | ||||
| Fatigue | 11/21 (52.4%) | 27/51 (52.9%) | ||
| Pyrexia | 2/21 (9.5%) | 4/51 (7.8%) | ||
| Influenza like illness | 0/21 (0%) | 5/51 (9.8%) | ||
| Thirst | 2/21 (9.5%) | 0/51 (0%) | ||
| Oedema peripheral | 6/21 (28.6%) | 4/51 (7.8%) | ||
| Gait disturbance | 3/21 (14.3%) | 1/51 (2%) | ||
| Chills | 0/21 (0%) | 5/51 (9.8%) | ||
| Infections and infestations | ||||
| Herpes zoster | 0/21 (0%) | 3/51 (5.9%) | ||
| Bronchitis | 0/21 (0%) | 3/51 (5.9%) | ||
| Sinusitis | 0/21 (0%) | 6/51 (11.8%) | ||
| Injury, poisoning and procedural complications | ||||
| Contusion | 3/21 (14.3%) | 2/51 (3.9%) | ||
| Investigations | ||||
| Haemoglobin decreased | 2/21 (9.5%) | 2/51 (3.9%) | ||
| Weight decreased | 1/21 (4.8%) | 7/51 (13.7%) | ||
| Aspartate aminotransferase increased | 3/21 (14.3%) | 4/51 (7.8%) | ||
| Blood alkaline phosphatase increased | 2/21 (9.5%) | 4/51 (7.8%) | ||
| Alanine aminotransferase increased | 3/21 (14.3%) | 5/51 (9.8%) | ||
| Metabolism and nutrition disorders | ||||
| Hypoglycaemia | 1/21 (4.8%) | 3/51 (5.9%) | ||
| Hyponatraemia | 3/21 (14.3%) | 1/51 (2%) | ||
| Decreased appetite | 5/21 (23.8%) | 14/51 (27.5%) | ||
| Dehydration | 2/21 (9.5%) | 1/51 (2%) | ||
| Hypophosphataemia | 1/21 (4.8%) | 3/51 (5.9%) | ||
| Hyperglycaemia | 4/21 (19%) | 4/51 (7.8%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Myalgia | 1/21 (4.8%) | 3/51 (5.9%) | ||
| Arthralgia | 2/21 (9.5%) | 3/51 (5.9%) | ||
| Neck pain | 0/21 (0%) | 4/51 (7.8%) | ||
| Pain in extremity | 3/21 (14.3%) | 5/51 (9.8%) | ||
| Back pain | 4/21 (19%) | 8/51 (15.7%) | ||
| Muscular weakness | 3/21 (14.3%) | 4/51 (7.8%) | ||
| Musculoskeletal stiffness | 2/21 (9.5%) | 3/51 (5.9%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Tumour pain | 2/21 (9.5%) | 0/51 (0%) | ||
| Nervous system disorders | ||||
| Dizziness | 2/21 (9.5%) | 11/51 (21.6%) | ||
| Dysgeusia | 0/21 (0%) | 4/51 (7.8%) | ||
| Paraesthesia | 3/21 (14.3%) | 1/51 (2%) | ||
| Brain oedema | 0/21 (0%) | 4/51 (7.8%) | ||
| Headache | 6/21 (28.6%) | 20/51 (39.2%) | ||
| Memory impairment | 0/21 (0%) | 5/51 (9.8%) | ||
| Aphasia | 1/21 (4.8%) | 3/51 (5.9%) | ||
| Convulsion | 1/21 (4.8%) | 5/51 (9.8%) | ||
| Hypoaesthesia | 1/21 (4.8%) | 4/51 (7.8%) | ||
| Psychiatric disorders | ||||
| Insomnia | 4/21 (19%) | 8/51 (15.7%) | ||
| Agitation | 1/21 (4.8%) | 3/51 (5.9%) | ||
| Confusional state | 1/21 (4.8%) | 4/51 (7.8%) | ||
| Renal and urinary disorders | ||||
| Polyuria | 2/21 (9.5%) | 0/51 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 2/21 (9.5%) | 11/51 (21.6%) | ||
| Dyspnoea | 2/21 (9.5%) | 5/51 (9.8%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 7/21 (33.3%) | 20/51 (39.2%) | ||
| Dry skin | 0/21 (0%) | 3/51 (5.9%) | ||
| Hyperhidrosis | 1/21 (4.8%) | 3/51 (5.9%) | ||
| Erythema | 0/21 (0%) | 3/51 (5.9%) | ||
| Pruritus | 6/21 (28.6%) | 17/51 (33.3%) | ||
| Vascular disorders | ||||
| Hypertension | 0/21 (0%) | 4/51 (7.8%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
| Name/Title | Bristol-Myers Squibb Study Director |
|---|---|
| Organization | Bristol-Myers Squibb |
| Phone | |
| Clinical.Trials@bms.com |
- CA184-042