TriangleNCT00094653 · CITED IN SOURCE DOCUMENTS
MDX-010 Antibody, MDX-1379 Melanoma Vaccine, or MDX-010/MDX-1379 Combination Treatment for Patients With Unresectable or Metastatic Melanoma
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2011-07-11
The purpose of this study is to determine the safety and efficacy of MDX-010 (ipilimumab, BMS-734016) (anti-CTLA4) in combination with MDX-1379 (gp100, BMS-734019) in patients with previously treated, unresectable Stage III or IV melanoma. Survival time will be evaluated, as well as patient responses and time to disease progression. Eligible patients are those who in response to a single regimen containing interleukin-2 (IL-2), dacarbazine, and/or temozolomide, have 1) relapsed following an objective response (partial response/complete response \[PR/CR\]); 2) failed to demonstrate an objective response (PR/CR); or 3) could not tolerate such a regimen due to unacceptable toxicity. Patients will be randomized into one of three groups, and will receive one of the following treatments: MDX-010 alone, MDX-1379 alone, or MDX-010 in combination with MDX-1379.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 in Combination With gp 100 Melanoma Peptide Vaccine Versus gp 100 Melanoma Peptide Vaccine Alone
Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 Monotherapy Versus gp100 Melanoma Peptide Vaccine Alone and MDX-010 in Combination With gp100 Melanoma Peptide Vaccine Versus MDX-010 Monotherapy
12-, 18-, and 24-Month Survival Rates
Progression Free Survival (PFS)
Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24
Time to Progression (TTP)
Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)
Determination of Best Overall Response Rate (BORR)
Time to Response
Duration of Response
Disease Control Rate (DCR)
Delayed Response (Response Beyond Week 24)
Change From Baseline in Health-Related Quality of Life (QOL) as Measured by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Instrument at Week 12
Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death
Percentage of Participants With Immune-Related Adverse Events (irAEs)
Percentage of Participants With Worst On-Study Hematological Abnormalities
Percentage of Participants With Worst On-Study Liver Abnormalities
Percentage of Participants With Worst On-Study Renal Abnormalities
Clinically Meaningful Changes in Vital Signs and Physical Examinations
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: * Diagnosed with malignant melanoma * Measurable unresectable Stage III or IV melanoma * HLA-A\*0201 positive * Previous treatment with \& failure/relapse/inability to tolerate IL-2, dacarbazine and/or temozolomide * At least 4 weeks since prior treatment * Negative pregnancy * Life expectancy greater than 4 months * Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1 * Required lab values * Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) negative Exclusion Criteria: * Prior malignancies which the patient has not been disease free for over 5 years, except treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or any other cancer * Ocular melanoma * Active, untreated central nervous system (CNS) metastasis * Prior treatment with MDX-010 (anti-CTLA4) antibody * Prior treatment with any cancer therapeutic vaccine * Active autoimmune disease or history of autoimmune disease * Pregnancy or nursing * Hypersensitivity to Incomplete Freund's Adjuvant (IFA) (Montanide ISA-51) * Underlying medical conditions deemed hazardous if treated with study drug * Concomitant therapy with anti-melanoma drugs, chemotherapies, other investigational therapies, chronic use of systemic corticosteroids * Unable to provide informed consent
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Melanoma Peptide Vaccine (MDX-1379) (gp100) + Placebo
- intervention Names
- Biological: MDX-1379 (gp100) Melanoma Peptide Vaccine
- label
- 1
- type
- ACTIVE_COMPARATOR
- description
- MDX-010 (ipilimumab) + MDX-1379 (gp100) (Melanoma Peptide Vaccine)
- intervention Names
- Drug: MDX-010 (anti-CTLA4) monoclonal antibody
- Biological: MDX-1379 (gp100) Melanoma Peptide Vaccine
- label
- 2
- type
- EXPERIMENTAL
- description
- MDX-010 (ipilimumab) + Placebo
- intervention Names
- Drug: MDX-010 (anti-CTLA4) monoclonal antibody
- label
- 3
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- 2
- 3
- description
- 3mg/kg (intravenous \[iv\] infusion over 90 minutes), every 3 weeks for 4 doses
- name
- MDX-010 (anti-CTLA4) monoclonal antibody
- other Names
- ipilimumab
- type
- DRUG
- arm Group Labels
- 1
- 2
- description
- 2mL (2 subcutaneous injections of 2 mL each, 1 to each thigh), every 3 weeks for 4 doses.
- name
- MDX-1379 (gp100) Melanoma Peptide Vaccine
- other Names
- melanoma peptide vaccine
- type
- BIOLOGICAL
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- TRIPLE
- who Masked
- PARTICIPANT
- CARE_PROVIDER
- INVESTIGATOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 1783
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- OS was defined as the time from randomization until death from any cause. If a participant did not expire, the subject was censored at the time of last contact (last known alive date). 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.
- measure
- Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 in Combination With gp 100 Melanoma Peptide Vaccine Versus gp 100 Melanoma Peptide Vaccine Alone
- time Frame
- From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)
- secondary Outcomes
- description
- OS was defined as the time from randomization until death from any cause. If a participant did not expire, the subject was censored at the time of last contact (last known alive date). 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.
- measure
- Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 Monotherapy Versus gp100 Melanoma Peptide Vaccine Alone and MDX-010 in Combination With gp100 Melanoma Peptide Vaccine Versus MDX-010 Monotherapy
- time Frame
- From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)
- description
- The probability that a subject is alive at 12 months, 18 months, and 24 months following randomization, estimated via the non-parametric method (Kaplan-Meier method). For calculating 95% CI, bootstrap method was used with 20000 simulated trials.
- measure
- 12-, 18-, and 24-Month Survival Rates
- time Frame
- Month 12, Month 18, Month 24
- description
- PFS was defined as the number of days between the date of randomization and the date of the progression or the date of death. A subject who died without prior progression was considered to have progressed on the date of death. PFS was determined by investigator. 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.
- measure
- Progression Free Survival (PFS)
- time Frame
- From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)
- description
- PFS at Week 12 was defined as the probability that the subject was progression-free at 12 weeks and 24 weeks following the start of randomization. It was computed via Kaplan-Meier method, truncated at Week 12 and Week 24. PFS was determined by investigator. 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.
- measure
- Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24
- time Frame
- Week 12, Week 24
- description
- TTP was defined as the number of days between the date of the randomization and date of PD or death due to PD. For subjects who had not progression and remained alive, TTP was censored on the date of last assessment; those who remained alive and had no recorded post-baseline assessment, TTP was censored on the date of randomization; those who remained alive and had randomized but were not treated, TTP was censored at the date of randomization; for those who died without reported disease progression, TTP was censored on the date of death.
- measure
- Time to Progression (TTP)
- time Frame
- from time of randomization to date of PD or death due to PD (end of the study was defined as the time at which 481 deaths were observed [264 weeks])
- description
- Investigator's assessment, modified World Health Organization criteria. CR: disappearance of all lesions by 2 consecutive observations \>=4 weeks apart, no evidence of PD. PR: \>=50% ↓ in sum of products of longest diameter \& greatest perpendicular diameter of all target lesions compared to baseline by 2 observations \>=4 weeks apart. SD: Neither sufficient ↓ to qualify for PR nor sufficient ↑ to qualify for PD. PD: ↑ \>=25% in sum of products of longest diameter \& greatest perpendicular diameter of target lesions compared to smallest recorded sum during study, or appearance of \>= 1 new lesion.
- measure
- Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)
- time Frame
- BOR was determined between Weeks 12 and Week 24 confirmation at least 4 weeks later at Cycle 1.
- description
- Response was based on the investigators' assessment using modified WHO criteria. BORR is defined as the number of subjects whose BOR is complete or partial response (CR or PR) divided by the total number of subjects in the group. BORR was comprised of responder and non-responder. The definition of a responder in BORR was either confirmed CR or PR, and a non-responder was defined as stable disease (SD), progressed disease (PD), unconfirmed CR (uCR), unconfirmed PR (uPR), and not evaluated.
- measure
- Determination of Best Overall Response Rate (BORR)
- time Frame
- Up to week 24
- description
- Time to response was defined as the number of days from the date of randomization to the date when measurement criteria are met for BOR of CR or PR, as determined by investigator.
- measure
- Time to Response
- time Frame
- From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)
- description
- Kaplan-Meier medians along with Brookmeyer and Crowley 95% confidence intervals (CI) for were computed. Duration of response was defined in subjects whose BOR was CR or PR as the number of days between the date of response (CR or PR) and the date of PD or the date of death (whichever occurs first).
- measure
- Duration of Response
- time Frame
- from time of initial drug administration to date of PD or death due to PD (the end of the study was defined as the time at which 481 deaths were observed [264 weeks])
- description
- Response was based on the investigators' assessment using modified WHO criteria. DCR is defined as the number of subjects whose BOR is CR, PR, or SD divided by the total number of subjects in the group.
- measure
- Disease Control Rate (DCR)
- time Frame
- Up to week 24
- description
- Response was based on the investigators' assessment using modified World Health Organization (WHO) criteria. Delayed response is defined as post Week 24 overall response for the subjects who have PD before or at Week 24. Evaluation of delayed overall response is compared to baseline assessment. Delayed response includes delayed late CR, delayed late PR, delayed late SD, continued PD, unknown, and missing after Week 24. The delayed response of CR and PR also must have been confirmed.
- measure
- Delayed Response (Response Beyond Week 24)
- time Frame
- from Week 24 to end of study (the end of the study was defined as the time at which 481 deaths were observed [264 weeks])
- description
- The 30 items were grouped into the following: 1 global QOL scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). All scores were linearly transformed to a 0 to 100 scale. For global QOL and functional items, a higher score represents a better level of functioning (100=best/0=worst). For symptom items, a higher score represents a higher level of symptoms (0=no symptom at all/100=very much severe).
- measure
- Change From Baseline in Health-Related Quality of Life (QOL) as Measured by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Instrument at Week 12
- time Frame
- Baseline (Day 1, Cycle1), Week 12
Full study description
- brief Summary
- The purpose of this study is to determine the safety and efficacy of MDX-010 (ipilimumab, BMS-734016) (anti-CTLA4) in combination with MDX-1379 (gp100, BMS-734019) in patients with previously treated, unresectable Stage III or IV melanoma. Survival time will be evaluated, as well as patient responses and time to disease progression. Eligible patients are those who in response to a single regimen containing interleukin-2 (IL-2), dacarbazine, and/or temozolomide, have 1) relapsed following an objective response (partial response/complete response \[PR/CR\]); 2) failed to demonstrate an objective response (PR/CR); or 3) could not tolerate such a regimen due to unacceptable toxicity. Patients will be randomized into one of three groups, and will receive one of the following treatments: MDX-010 alone, MDX-1379 alone, or MDX-010 in combination with MDX-1379.
- detailed Description
- Melanoma accounts for approximately 5% of all skin cancers in the United States, but it accounts for about 75% of all skin cancer deaths. In 2004, the expected prevalence of melanoma is 627,252, with about 119,178 of these cases being Stage III or IV (metastatic melanoma). First line treatments for metastatic melanoma, usually IL-2, dacarbazine and/or temozolomide, are associated with significant toxicities. MDX-010 (anti-CTLA4) antibodies are designed to keep the immune system running by blocking CTLA-4 from down-regulating T cell activation. MDX-1379 is made up of two peptides that are pieces of a bigger melanoma protein (gp100). These peptides bind to HLA-A2 which is then recognized by T cells.
Source references
- references
- citation
- Larkin J, Hatswell AJ, Nathan P, Lebmeier M, Lee D. The Predicted Impact of Ipilimumab Usage on Survival in Previously Treated Advanced or Metastatic Melanoma in the UK. PLoS One. 2015 Dec 23;10(12):e0145524. doi: 10.1371/journal.pone.0145524. eCollection 2015.
- pmid
- 26700304
- type
- DERIVED
- citation
- Koguchi Y, Hoen HM, Bambina SA, Rynning MD, Fuerstenberg RK, Curti BD, Urba WJ, Milburn C, Bahjat FR, Korman AJ, Bahjat KS. Serum Immunoregulatory Proteins as Predictors of Overall Survival of Metastatic Melanoma Patients Treated with Ipilimumab. Cancer Res. 2015 Dec 1;75(23):5084-92. doi: 10.1158/0008-5472.CAN-15-2303.
- pmid
- 26627641
- type
- DERIVED
- citation
- Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, Patt D, Chen TT, Berman DM, Wolchok JD. Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma. J Clin Oncol. 2015 Jun 10;33(17):1889-94. doi: 10.1200/JCO.2014.56.2736. Epub 2015 Feb 9.
- pmid
- 25667295
- type
- DERIVED
- citation
- Johnson DB, Friedman DL, Berry E, Decker I, Ye F, Zhao S, Morgans AK, Puzanov I, Sosman JA, Lovly CM. Survivorship in Immune Therapy: Assessing Chronic Immune Toxicities, Health Outcomes, and Functional Status among Long-term Ipilimumab Survivors at a Single Referral Center. Cancer Immunol Res. 2015 May;3(5):464-9. doi: 10.1158/2326-6066.CIR-14-0217. Epub 2015 Feb 3.
- pmid
- 25649350
- type
- DERIVED
- citation
- Hatswell AJ, Pennington B, Pericleous L, Rowen D, Lebmeier M, Lee D. Patient-reported utilities in advanced or metastatic melanoma, including analysis of utilities by time to death. Health Qual Life Outcomes. 2014 Sep 10;12:140. doi: 10.1186/s12955-014-0140-1.
- pmid
- 25214238
- type
- DERIVED
- citation
- McDermott D, Haanen J, Chen TT, Lorigan P, O'Day S; MDX010-20 investigators. Efficacy and safety of ipilimumab in metastatic melanoma patients surviving more than 2 years following treatment in a phase III trial (MDX010-20). Ann Oncol. 2013 Oct;24(10):2694-2698. doi: 10.1093/annonc/mdt291. Epub 2013 Aug 13.
- pmid
- 23942774
- type
- DERIVED
- citation
- Robert C, Schadendorf D, Messina M, Hodi FS, O'Day S; MDX010-20 investigators. Efficacy and safety of retreatment with ipilimumab in patients with pretreated advanced melanoma who progressed after initially achieving disease control. Clin Cancer Res. 2013 Apr 15;19(8):2232-9. doi: 10.1158/1078-0432.CCR-12-3080. Epub 2013 Feb 26.
- pmid
- 23444228
- type
- DERIVED
- citation
- Weber JS, Dummer R, de Pril V, Lebbe C, Hodi FS; MDX010-20 Investigators. Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: detailed safety analysis from a phase 3 trial in patients with advanced melanoma. Cancer. 2013 May 1;119(9):1675-82. doi: 10.1002/cncr.27969. Epub 2013 Feb 7.
- pmid
- 23400564
- type
- DERIVED
- citation
- Revicki DA, van den Eertwegh AJ, Lorigan P, Lebbe C, Linette G, Ottensmeier CH, Safikhani S, Messina M, Hoos A, Wagner S, Kotapati S. Health related quality of life outcomes for unresectable stage III or IV melanoma patients receiving ipilimumab treatment. Health Qual Life Outcomes. 2012 Jun 13;10:66. doi: 10.1186/1477-7525-10-66.
- pmid
- 22694829
- type
- DERIVED
- citation
- Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Aug 19;363(8):711-23. doi: 10.1056/NEJMoa1003466. Epub 2010 Jun 5.
- pmid
- 20525992
- type
- DERIVED
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-eec9041a2f44e056c6ea
- requested nct id
- NCT00094653
- primary nct id
- NCT00094653
- source kind
- fda_spl_label
- source record id
- 72755838-4a55-4245-949e-16cea13f2584
- source file sha256
- a4bef6778baed183e5bcf581938b0b23d3576dfd9eb6150f2904934a750c5fef
- payload sha256
- 05a1f152d6abeb4a9d1a706cf8408f0c4664d538393efbeae052932e6e754280
- payload
- application numbers
- BLA125377
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-eec9041a2f44e056c6ea
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT00094653
- occurrences
- context exact
- 14.1 Unresectable or Metastatic Melanoma The efficacy of YERVOY was investigated in a Study MDX010-20, a randomized (3:1:1), double-blind, double-dummy trial (NCT00094653) that included patients with unresectable or metastatic melanoma previously treated with one or more of the following: aldesleukin, dacarbazine, temozolomide,
- end
- 190
- exact text
- NCT00094653
- start
- 179
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00400.json
- source file sha256
- a4bef6778baed183e5bcf581938b0b23d3576dfd9eb6150f2904934a750c5fef
- source json pointer
- /results/51/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 72755838-4a55-4245-949e-16cea13f2584
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 658a921a002e81a6b55202efcb78091c2f2526215217a47cb445aaf003f3b7ac
- spl effective time
- 20260820
- spl set id
- 2265ef30-253e-11df-8a39-0800200c9a66
Preserved source evidence · Not medical advice