Skip to content
Triangle logo TriangleGet started
← Study library

NCT00636168 · CITED IN SOURCE DOCUMENTS

Efficacy Study of Ipilimumab Versus Placebo to Prevent Recurrence After Complete Resection of High Risk Stage III 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
2019-12-17

The purpose of the study is to determine if ipilimumab is effective in preventing or delaying recurrence and prolongs survival after complete resection of high risk stage III melanoma

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.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Recurrence Free Survival (RFS) Per Independent Review Committee (IRC) in the Intent to Treat (ITT) Population

→

outcome · POSTED

Number of Participants With Recurrence or Death as Per Independent Review Committee (IRC) in the Intent to Treat (ITT) Population

→

outcome · POSTED

Recurrence-Free Survival (RFS) Rates Per IRC at 1 Year, 2 Years, and 3 Years in the ITT Population

→

outcome · POSTED

Distant Metastasis-Free Survival (DMFS) Per Independent Review Committee (IRC) in the Intent to Treat (ITT) Population

→

outcome · POSTED

Number of Participants With Distant Metastasis-Free Survival (DMFS) Per Independent Review Committee (IRC) in the Intent to Treat (ITT) Population

→

outcome · POSTED

Distant Metastasis-Free Survival (DMFS) Rates Per IRC at 1 Year, 2 Years, 3 Years, 4 Years and 5 Years in the ITT Population

→

outcome · POSTED

Overall Survival in the Intent to Treat (ITT) Population

→

outcome · POSTED

Rate of Overall Survival (OS)

→

outcome · POSTED

Number of Participants With On-Study Adverse Events (AEs) Leading to Discontinuation of Treatment, Serious AEs (SAEs), Drug-Related SAEs, Immune-related AEs (irAEs), Immune-mediated Adverse Reactions (imARs), Deaths in Treated Population

→

outcome · POSTED

Number of Participants With Serious Adverse Events (SAEs), Non-serious AEs (NSAEs) and Number of Deaths: Overall Study

→

outcome · POSTED

Exposure Adjusted Incidence Rate of Adverse Events Including Multiple Occurrences of Unique Events

→

outcome · POSTED

Mean Change From Baseline in Global Health Status Scores at Each Assessment Timepoint

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→
Who could take part
eligibility Criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: * Age ≥ 18 years * Complete and adequate resection of Stage III melanoma with histologically confirmed melanoma metastatic to lymph node * Disease-free * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 * Randomization within 12 weeks of surgery Exclusion Criteria: * Prior therapy for melanoma except surgery * Auto-immune disease
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. intervention Names
    1. Drug: ipilimumab
    label
    A
    type
    ACTIVE_COMPARATOR
  2. intervention Names
    1. Drug: Placebo
    label
    B
    type
    PLACEBO_COMPARATOR
interventions
  1. arm Group Labels
    1. A
    description
    IV solution, IV, 10 mg/kg, 4x every 21 days, then starting from Week 24 every 12 weeks until Week 156 (3 years), disease recurrence, unacceptable toxicity or patient withdrawal
    name
    ipilimumab
    other Names
    1. BMS-734016
    2. MDX-010
    type
    DRUG
  2. arm Group Labels
    1. B
    description
    IV solution, IV, 10 mg/kg, 4x every 21 days then starting from Week 24 every 12 weeks until Week 156 (3 years), disease recurrence, unacceptable toxicity or patient withdrawal
    name
    Placebo
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
DOUBLE
who Masked
  1. PARTICIPANT
  2. INVESTIGATOR
primary Purpose
TREATMENT
Enrollment
count
1211
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Recurrence free survival (RFS) was programmatically determined based on the disease recurrence data provided by the IRC and was defined as the time between the date of randomization and the date of first recurrence or death (whatever the cause), whichever occurred first. A participant who died without reported recurrence was considered to have recurrence on the date of death. For those participants who remained alive and recurrence-free, RFS was censored on the date of last evaluable post-randomization tumor assessment. For those who remained alive and had no recorded post-randomization tumor assessment, RFS was censored on the day of randomization. Participants with disease at baseline were considered to have an event on the day of randomization. Computerized tomography (CT) and magnetic resonance imaging (MRI) were mandatory to establish recurrence. The primary analysis was event-driven and planned when at least 512 RFS events assessed per IRC were collected.
    measure
    Recurrence Free Survival (RFS) Per Independent Review Committee (IRC) in the Intent to Treat (ITT) Population
    time Frame
    Date of randomization to first date of recurrence or death or last available disease assessment with RFS data up to 5 years. Median follow-up was 2.7 years.
  2. description
    Recurrence was defined as appearance of one or more new melanoma lesions: local, regional or distant metastasis. Computerized tomography (CT) and magnetic resonance imaging (MRI) were mandatory to establish recurrence. A participant who died without reported recurrence was considered to have recurred on the date of death. Disease was assessed at randomization and every 12 weeks (±2 weeks) for 3 years, then every 24 weeks until documented distant progression.
    measure
    Number of Participants With Recurrence or Death as Per Independent Review Committee (IRC) in the Intent to Treat (ITT) Population
    time Frame
    Date of randomization to first date of recurrence or death or last available disease assessment with RFS data upto 5 years. Median follow-up was 2.7 years.
  3. description
    Yearly recurrence-free survival rates, eg. at 1 year, defined as the probability that a participant was recurrence-free at 1 year following randomization, were estimated for each treatment group using the Kaplan-Meier product-limit method, along with their corresponding log-log transformed 95% confidence intervals. RFS was defined as the time between the date of randomization and the date of first recurrence or death (whatever the cause), whichever occurred first. A participant who died without reported recurrence was considered to have recurrence on the date of death. For those who remained alive and recurrence-free, RFS was censored on the date of last evaluable post-randomization tumor assessment. For those who remained alive and had no recorded post-randomization tumor assessment, RFS was censored on the day of randomization. Participants with disease at baseline were considered to have an event on the day of randomization. CT and MRI were mandatory to establish recurrence.
    measure
    Recurrence-Free Survival (RFS) Rates Per IRC at 1 Year, 2 Years, and 3 Years in the ITT Population
    time Frame
    At years 1, 2, and 3
secondary Outcomes
  1. description
    Distant Metastasis-Free Survival (DMFS) was programmatically determined based on the first date of distant metastasis provided by the IRC and was defined as the time between the date of randomization and the date of first distant metastasis or death (whatever the cause), whichever occurred first. A participant who died without reported disease distant metastasis was considered to have distant metastasis on the date of death. For those who remained alive and metastasis-free, DMFS was censored on the date of last evaluable post-randomization tumor assessment. For those who remained alive and had no recorded post-randomization tumor assessment, DMFS was censored on the day of randomization. Participants with disease at baseline were considered to have an event on the day of randomization. Disease was assessed at baseline (randomization) and every 12 weeks (±2 weeks) for 3 years, then every 24 weeks until documented distant progression.
    measure
    Distant Metastasis-Free Survival (DMFS) Per Independent Review Committee (IRC) in the Intent to Treat (ITT) Population
    time Frame
    From June 2008 to January 2016 (approximately 90 months)
  2. description
    DMFS was programmatically determined based on the first date of distant metastasis provided by the IRC and was defined as the time between the date of randomization and the date of first distant metastasis or death (whatever the cause), whichever occurred first. A participant who died without reported disease distant metastasis was considered to have distant metastasis on the date of death. For those who remained alive and metastasis-free, DMFS was censored on the date of last evaluable post-randomization tumor assessment. For those who remained alive and had no recorded post-randomization tumor assessment, DMFS was censored on the day of randomization. Participants with disease at baseline were considered to have an event on the day of randomization. Disease was assessed at baseline (randomization) and every 12 weeks (2 weeks) for 3 years, then every 24 weeks until documented distant progression.
    measure
    Number of Participants With Distant Metastasis-Free Survival (DMFS) Per Independent Review Committee (IRC) in the Intent to Treat (ITT) Population
    time Frame
    From June 2008 to January 2016 (approximately 90 months)
  3. description
    Yearly distant metastasis-free survival rates, e.g. at 1 year, defined as the probability that a participant was alive at 1 year following randomization, were estimated via the Kaplan-Meier method. Distant Metastasis-Free Survival (DMFS) was programmatically determined based on the first date of distant metastasis provided by the IRC and was defined as the time between the date of randomization and the date of first distant metastasis or death (whatever the cause), whichever occurred first. A participant who died without reported disease distant metastasis was considered to have distant metastasis on the date of death. For those who remained alive and metastasis-free, DMFS was censored on the date of last evaluable post-randomization tumor assessment. For those who remained alive and had no recorded post-randomization tumor assessment. Participants with disease at baseline were considered to have an event on the day of randomization.
    measure
    Distant Metastasis-Free Survival (DMFS) Rates Per IRC at 1 Year, 2 Years, 3 Years, 4 Years and 5 Years in the ITT Population
    time Frame
    At years 1, 2, 3, 4 and 5
  4. description
    OS was defined as the time from the date of randomization to the date of death. For those participants who had not died, OS was censored at the recorded last non-missing date of contact for which the participant was known to be alive.
    measure
    Overall Survival in the Intent to Treat (ITT) Population
    time Frame
    From June 2008 to January 2016 (approximately 90 months)
  5. description
    OS was defined as the time from the date of randomization to the date of death. For those participants who had not died, OS was censored at the recorded last non-missing date of contact for which the participant was known to be alive.Yearly survival rates, e.g. at 3 years, defined as the probability that a participant was alive at 3 years following randomization, were estimated via the Kaplan-Meier method
    measure
    Rate of Overall Survival (OS)
    time Frame
    From date of randomization to date of death, assessed up to 9 years
  6. description
    AEs: Medical Dictionary for Regulatory Activities (MedDRA) version 16.1. irAEs=unknown etiology consistent with an immune phenomenon, considered as causally related to drug. imARs=based on investigator's assessment of immune-mediated etiology \[excluding novel maintenance events (ie, patients with imARs occurring for the first time during maintenance)\]. 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. Drug-related (D-R)=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling, Gr 5=Death.
    measure
    Number of Participants With On-Study Adverse Events (AEs) Leading to Discontinuation of Treatment, Serious AEs (SAEs), Drug-Related SAEs, Immune-related AEs (irAEs), Immune-mediated Adverse Reactions (imARs), Deaths in Treated Population
    time Frame
    Day 1 up to 70 days after last dose; up to 5 years
  7. description
    AEs: Medical Dictionary for Regulatory Activities (MedDRA) version 16.1. 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.
    measure
    Number of Participants With Serious Adverse Events (SAEs), Non-serious AEs (NSAEs) and Number of Deaths: Overall Study
    time Frame
    SAEs and NSAEs: Day 1 up to 70 days after last dose(safety window). Deaths: All deaths regardless of 70 day safety window.Up to 10 years
  8. description
    P-Y = person-years of exposure. Incidence rate per 100 person-years of exposure (IR/100 P-Y) was calculated as event count \* 100 /person-years of exposure. MedDRA Version: 19. Duplicate AEs have been eliminated and overlapping and contiguous occurrences of the same event have been collapsed.
    measure
    Exposure Adjusted Incidence Rate of Adverse Events Including Multiple Occurrences of Unique Events
    time Frame
    Day 1 up to 70 days after last dose; up to 5 years
  9. description
    Global health status was measured using European Organization for Research and Treatment of Cancer (EORTC) Quality Life Questionnaire (QLQ) C-30. This health related quality of life (HRQoL) questionnaire was comprised of 15 questions on functional scales, 13 questions on symptom scales and 2 on global health status scale. Global Health Status used a 7 point Likert-type scale of 1 (Very poor) to 7 (Excellent). All scales linearly transformed to 0-100 scales. Higher scores for Global Health Status indicate better HRQoL. An increase from baseline indicates improvement in HRQoL compared to baseline. HRQoL was administered within 1 week prior to first dose (baseline) and on Days 22, 43, 64 (+/- 3 days), Week 24 and every 12 weeks up to 2 years, independent of disease progression.
    measure
    Mean Change From Baseline in Global Health Status Scores at Each Assessment Timepoint
    time Frame
    Baseline up to 2 years from randomization
Full study description
brief Summary
The purpose of the study is to determine if ipilimumab is effective in preventing or delaying recurrence and prolongs survival after complete resection of high risk stage III melanoma
Source references
references
  1. citation
    Weber JS, Middleton MR, Yates G, Sharpe DJ, Kurt M, Lobo M, Moshyk A, Vanderpuye-Orgle J, Mohr P. Estimating Long-Term Survivorship Rates Among Patients With Resected Stage III/IV Melanoma: Analyses From CheckMate 238 and European Organization for Research and Treatment of Cancer 18071 Trials. J Clin Oncol. 2025 Mar 10;43(8):929-937. doi: 10.1200/JCO.24.00237. Epub 2024 Oct 8.
    pmid
    39378385
    type
    DERIVED
  2. citation
    Weber JS, Ascierto PA, Middleton MR, Hennicken D, Zoffoli R, Pieters A, Amadi A, Kupas K, Kotapati S, Moshyk A, Schadendorf D. Indirect treatment comparison of nivolumab versus placebo as adjuvant treatment for resected melanoma. Eur J Cancer. 2021 Nov;158:225-233. doi: 10.1016/j.ejca.2021.08.028. Epub 2021 Oct 15.
    pmid
    34663559
    type
    DERIVED
  3. citation
    Coens C, Suciu S, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, Richards JM, Lebbe C, Ferraresi V, Smylie M, Weber JS, Maio M, Bottomley A, Kotapati S, de Pril V, Testori A, Eggermont AMM. Health-related quality of life with adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): secondary outcomes of a multinational, randomised, double-blind, phase 3 trial. Lancet Oncol. 2017 Mar;18(3):393-403. doi: 10.1016/S1470-2045(17)30015-3. Epub 2017 Feb 3.
    pmid
    28162999
    type
    DERIVED
  4. citation
    Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, Richards JM, Lebbe C, Ferraresi V, Smylie M, Weber JS, Maio M, Bastholt L, Mortier L, Thomas L, Tahir S, Hauschild A, Hassel JC, Hodi FS, Taitt C, de Pril V, de Schaetzen G, Suciu S, Testori A. Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy. N Engl J Med. 2016 Nov 10;375(19):1845-1855. doi: 10.1056/NEJMoa1611299. Epub 2016 Oct 7.
    pmid
    27717298
    type
    DERIVED
  5. citation
    Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, Richards JM, Lebbe C, Ferraresi V, Smylie M, Weber JS, Maio M, Konto C, Hoos A, de Pril V, Gurunath RK, de Schaetzen G, Suciu S, Testori A. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015 May;16(5):522-30. doi: 10.1016/S1470-2045(15)70122-1. Epub 2015 Mar 31.
    pmid
    25840693
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-160d4500ff6b98d5d6a0
      requested nct id
      NCT00636168
      primary nct id
      NCT00636168
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source file sha256
      719775cb8adafac157fae579695d5225c0957562da450bf6f429433b407c581a
      payload sha256
      ceed81772c37af96ec77284619aa8d7a1bd8ac5748ebfff26dd9f469d5346dc8
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-160d4500ff6b98d5d6a0
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT00636168
      occurrences
      1. context exact
        macroscopically positive.</p> </section> </section> </section><section id="_900"> <h3 id="_900_toc">Adjuvant Therapy</h3> <p id="NCT00636168" tabindex="-1">Adjuvant therapy options for patients at high risk of recurrence after complete resection include checkpoint inhibitors and combination signal t
        end
        106927
        exact text
        NCT00636168
        start
        106916
      2. context exact
        n (FDA) as adjuvant therapy. It has demonstrated improved overall survival (OS) when given at 10 mg/kg (ipi10), compared with placebo (<a href="/clinicaltrials/NCT00636168">EORTC 18071</a> [NCT00636168]).[<a href="#cit/section_4.18">18</a>] However, ipi10 has significant toxicity at this dose. The North American Intergroup Trial
        end
        107390
        exact text
        NCT00636168
        start
        107379
      3. context exact
        t has demonstrated improved overall survival (OS) when given at 10 mg/kg (ipi10), compared with placebo (<a href="/clinicaltrials/NCT00636168">EORTC 18071</a> [NCT00636168]).[<a href="#cit/section_4.18">18</a>] However, ipi10 has significant toxicity at this dose. The North American Intergroup Trial <a href="/clinicaltrials/NCT01
        end
        107420
        exact text
        NCT00636168
        start
        107409
      4. context exact
        to be approved by the FDA as adjuvant therapy. It has demonstrated improved OS when given at 10 mg/kg (ipi10), compared with placebo (<a href="/clinicaltrials/NCT00636168">EORTC 18071</a> [NCT00636168]).[<a href="#cit/section_9.22">22</a>] However, ipi10 has significant toxicity at this dose. The North American Intergroup Trial
        end
        211343
        exact text
        NCT00636168
        start
        211332
      5. context exact
        adjuvant therapy. It has demonstrated improved OS when given at 10 mg/kg (ipi10), compared with placebo (<a href="/clinicaltrials/NCT00636168">EORTC 18071</a> [NCT00636168]).[<a href="#cit/section_9.22">22</a>] However, ipi10 has significant toxicity at this dose. The North American Intergroup Trial <a href="/clinicaltrials/NCT01
        end
        211373
        exact text
        NCT00636168
        start
        211362
      6. context exact
        emonstrated that nivolumab was superior to ipi10 in improving RFS, with OS data still maturing.</p></li><li>In a multinational double-blind trial (EORTC 18071 [NCT00636168]), patients with stage III melanoma, who had complete resection, were randomly assigned (1:1) to receive either ipilimumab or placebo.[<a href="#cit/section_9.
        end
        224137
        exact text
        NCT00636168
        start
        224126
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/498bb790d49a11b74e.html
      source file sha256
      719775cb8adafac157fae579695d5225c0957562da450bf6f429433b407c581a
      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:22:15.974415+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      10578b000af9132c9cfe25a00f45be6680f43e992f5c12f2b6697492c4a5ca2e
      source title
      Melanoma Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: May 2, 2025
        datetime
        2025-05-02T12:00:00Z
        display
        May 2, 2025

    Preserved source evidence · Not medical advice