Trial record 2 of 4 for:    Study of Adjuvant Ipilimumab Anti-CTLA4

Efficacy Study of Ipilimumab Versus Placebo to Prevent Recurrence After Complete Resection of High Risk Stage III Melanoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00636168
First received: March 7, 2008
Last updated: August 18, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
High Risk Stage III Melanoma
Drug: ipilimumab
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Adjuvant Immunotherapy With Anti-CTLA-4 Monoclonal Antibody (Ipilimumab) Versus Placebo After Complete Resection of High Risk Stage III Melanoma: A Randomized, Double-blind Phase 3 Trial of the EORTC Melanoma Group

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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 patient who died without reported recurrence was considered to have recurrence on the date of death. For those patients 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. Patients 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.

  • Number of Patients 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. ] [ Designated as safety issue: No ]
    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 patient 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.

  • Recurrence-Free Survival (RFS) Rates Per IRC at 1 Year, 2 Years, and 3 Years in the ITT Population [ Time Frame: Randomization up to Years 1, 2, and 3 ] [ Designated as safety issue: No ]
    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 patient 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. Patients with disease at baseline were considered to have an event on the day of randomization. CT and MRI were mandatory to establish recurrence. 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.


Secondary Outcome Measures:
  • Number of Patients With Distant Metastasis-Free Survival (DMFS) [ Time Frame: Date of randomization to date of DMFS, up to 5 years ] [ Designated as safety issue: No ]
    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 patient 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. Patients 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.

  • Number of Participants With Overall Survival (OS) [ Time Frame: date of randomization to date of death or last known alive date with OS data upto 5 years. ] [ Designated as safety issue: No ]
    OS was defined as the time from the date of randomization to the date of death. For those participants who have not died, OS was censored at the recorded last non-missing date of contact for which the participant was known to be alive.

  • Number of Patients With 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 or last known alive date for patients still being dosed; up to 5 years ] [ Designated as safety issue: Yes ]
    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.

  • Exposure Adjusted Incidence Rate of Adverse Events Including Multiple Occurrences of Unique Events [ Time Frame: Day 1 up to 70 days after last dose or last known alive date for participants still being dosed; up to 5 years ] [ Designated as safety issue: Yes ]
    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: 16.1. Duplicate AEs have been eliminated and overlapping and contiguous occurrences of the same event have been collapsed.

  • Mean Change From Baseline in Global Health Status Scores at Each Assessment Timepoint [ Time Frame: Baseline up to 2 years from randomization ] [ Designated as safety issue: No ]
    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.


Enrollment: 1211
Study Start Date: May 2008
Estimated Study Completion Date: September 2019
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A Drug: ipilimumab
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
Other Names:
  • BMS-734016
  • MDX-010
Placebo Comparator: B Drug: Placebo
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00636168

  Show 97 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00636168     History of Changes
Other Study ID Numbers: CA184-029, EORTC 18071
Study First Received: March 7, 2008
Results First Received: July 25, 2014
Last Updated: August 18, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
European Union: European Medicines Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Czech Republic: State Institute for Drug Control
Denmark: Laegmiddeistyrelsen
Finland: Laakelaitos
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: Isituto Supiore di Sanita Commissione per l'accertamento dei requisti dei prodotti farmaceuticidi nuova istituzione
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Norway: Statens legemiddelverk
Poland: Urzad Rejestracji Produktow Leczniczych Wyrobow Medycznych i Produktow Biobojczych
Spain: AEMPS - Agencia Espanola der Medicamento y Productos Sanitarios
Sweden: Ladenmedeisverket
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

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

ClinicalTrials.gov processed this record on September 18, 2014