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A Phase III Study to Test the Benefit of a New Kind of Anti-cancer Treatment in Patients With Melanoma, After Surgical Removal of Their Tumor

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00796445
Recruitment Status : Terminated (The study was terminated early following assessment of the two co-primary endpoints showing the lack of efficacy of the study product.)
First Posted : November 24, 2008
Results First Posted : March 19, 2019
Last Update Posted : March 19, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE November 21, 2008
First Posted Date  ICMJE November 24, 2008
Results First Submitted Date  ICMJE September 30, 2016
Results First Posted Date  ICMJE March 19, 2019
Last Update Posted Date March 19, 2019
Actual Study Start Date  ICMJE December 1, 2008
Actual Primary Completion Date January 27, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 22, 2019)
  • Disease Free Survival (DFS) [ Time Frame: At Final analysis (Month 30 = Year 2.5) ]
    DFS = time from randomization to the date of first disease recurrence (as assessed by investigator) or the date of death (whatever cause), whichever occurred first. DFS was expressed as the sum of follow-up periods, in years, until the first occurrence of a recurrence/death. Types of recurrence to be considered as an event included loco-regional and distant metastases. Any death occurring without prior documentation of tumor recurrence was considered as an event (not censored in the stat. analysis) as this approach was less prone to introduce bias. If no event occurred by the time of analysis, then the time to event was censored at the last assessment date (tumor assessment/visit) of the patient. Any new primary cancer at another site, including second primary melanoma, was not considered as a recurrence and had to be reported as a Serious Adverse Event (SAE).
  • Disease Free Survival (DFS) [ Time Frame: At follow-up analysis (up to Year 5) ]
    DFS = time from randomization to the date of first disease recurrence (as assessed by investigator) or the date of death (whatever cause), whichever occurred first. DFS was expressed as the sum of follow-up periods, in years, until the first occurrence of a recurrence/death. Types of recurrence to be considered as an event included loco-regional and distant metastases. Any death occurring without prior documentation of tumor recurrence was considered as an event (not censored in the stat. analysis) as this approach was less prone to introduce bias. If no event occurred by the time of analysis, then the time to event was censored at the last assessment date (tumor assessment/visit) of the patient. Any new primary cancer at another site, including second primary melanoma, was not considered as a recurrence and had to be reported as a Serious Adverse Event (SAE).
Original Primary Outcome Measures  ICMJE
 (submitted: November 21, 2008)
Disease Free Survival [ Time Frame: Once the pre-defined number of events is reached ]
Change History Complete list of historical versions of study NCT00796445 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 22, 2019)
  • Overall Survival (OS) [ Time Frame: At Final analysis (Month 30 = Year 2.5) and at follow-up analysis (up to Year 5) ]
    Overall Survival (OS) was defined as the interval from randomization to the date of death, irrespective of the cause of death. OS was expressed as the sum of follow-up periods, in years, until the occurrence of death.
  • Disease-free Specific Survival (DFSS) [ Time Frame: At Final analysis (Month 30 = Year 2.5) ]
    Disease Free Specific Survival (DFSS) was defined as the interval from randomization to the date of first recurrence of disease or date of death due to melanoma (cause as assessed by investigator), whichever occurred first. DFSS was expressed as the sum of follow-up periods, in years, until the first occurrence of a recurrence/death. Patients who died due to a cause other than the disease under study and patients alive at the time of analysis were censored on the date of last assessment (visit or tumor assessment).
  • Distant Metastasis-free Survival (DMFS) [ Time Frame: At Final analysis (Month 30 = Year 2.5) ]
    Distant Metastasis Free Survival (DMFS) was defined as the interval from randomization to the date of first distant metastasis or date of death, whichever occurred first. DMFS was expressed as the sum of follow-up periods, in years, until the first occurrence of distant metastasis/death. Patients alive and without distant metastases were censored at the date of last assessment (visit or tumor assessment, or date of last tumor assessment as documented during the yearly contact follow-up period).
  • Health-related Quality of Life [ Time Frame: At Weeks 0, 6, 12 [on the day of and the day after treatment administration (TA)], at Month 6, 9, 12, 24, at the Concluding visit (Month 30) + 6 months and +12 Months and at disease recurrence ]
    The assessment of health-related quality of life was restricted to patients who consented to study participation after Protocol Amendment 1 became effective at their study site, and for whom a validated version of the Euro Quality of Life-5D (EQ-5D) questionnaire was available in their native language. The EQ-5D comprises a 5-dimensional descriptive system (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), where each item has 3 levels and together they define 243 possible health states. For each health state, a value (utility) was determined by using an additive algorithm. These utility scores were calculated for each patient at each timepoint at which an EQ-5D questionnaire was completed. The score had a maximum value of 1.0 corresponding to full health level, while lower scores, down to a minimum value of 0.0 reflected degradation in the health-related quality of life.
  • Number of Subjects With Anti-MAGE-A3 Antibody Concentrations Above the Cut-off Value [ Time Frame: At Weeks 0, 6, 12, 36, 48 72, 120 (Concluding visit) and at Week 120 + 6 months ]
    The cut-off value was 27 Enzyme-Linked Immunosorbent Assay (ELISA) units per milliliter (EL.U/mL).
  • Anti-MAGE-A3 Antibody Geometric Mean Concentrations [ Time Frame: At Weeks 0, 6, 12, 36, 48 72, 120 (Concluding visit) and at Month 120 + 6 months ]
    Anti-MAGE-A3 antibody concentrations were presented as geometric mean concentrations (GMC) and expressed in EL.U/mL.
  • Number of Subjects With Anti-MAGE-A3 Antibody Response [ Time Frame: At Weeks 0, 6, 12, 36, 48 72, 120 (Concluding visit) and at Month 120 + 6 months ]
    Treatment response defined as: - For initially seronegative patients: post-vaccination antibody concentration ≥ 27 EL.U/mL; - For initially seropositive patients: post-vaccination antibody concentration ≥ 2 fold the pre-vaccination antibody concentration.
  • Number of Subjects With Abnormal Haematological and Biochemical Parameters [ Time Frame: Within the 31-day (Days 0-30) post-vaccination period, at follow-up analysis ]
    Laboratory abnormalities belong to hematological and biochemical parameters such as: alanine aminotransferase [ALT], asparatate aminostransferase [AST], alkaline phoshatase [AP], bilirubin [BIL], creatinine [CREA], hemoglobin [HGB], leukocytes [LEU], lymphopenia [LYMPH], neutrophils [NEU], platelets [PLA]. Parameter grades (Grade [G] 0, 1, 2, 3, 4, Unknown) were compared to each baseline parameter grade (G Unknown, 0, 1, 2, 3), as defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 of August 9, 2006.
  • Number of Subjects With Any Adverse Events (AEs) [ Time Frame: Within the 31-day (Days 0-30) follow-up period after vaccination - at Follow-up analysis ]
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
  • Number of Subjects With Any Serious Adverse Events (SAEs) [ Time Frame: From Day 0 up to study end (Year 5) ]
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
  • Number of Subjects With Potential Immune-mediated Diseases (pIMDs) [ Time Frame: Within the 31-day (Days 0-30) post-administration period, at Follow-up analysis ]
    Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2008)
  • Overall Survival [ Time Frame: At the time of analysis ]
  • Disease-free specific survival [ Time Frame: At the time of analysis ]
  • Distant metastasis-free survival [ Time Frame: At the time of analysis ]
  • Anti-MAGE-A3 and anti-protein D seropositivity status. [ Time Frame: Post-treatment and 1 year after concluding visit. ]
  • Occurrence of adverse events including abnormal haematological and biochemical parameters. [ Time Frame: Up to 30 days after each study dose. ]
  • Occurrence of serious adverse events and autoimmunity events. [ Time Frame: During the whole study duration up to 30 days after the last administration of study treatment. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase III Study to Test the Benefit of a New Kind of Anti-cancer Treatment in Patients With Melanoma, After Surgical Removal of Their Tumor
Official Title  ICMJE GSK 2132231A Antigen-Specific Cancer Immunotherapeutic as Adjuvant Therapy in Patients With Resected Melanoma
Brief Summary

The purpose of this clinical trial is to evaluate the benefit of the immunotherapeutic product GSK 2132231A in preventing disease relapse when given to melanoma patients, after surgical removal of their tumor.

This Protocol Posting has been updated following Amendments 1 of the Protocol, March 2010. The impacted sections are outcome measures and entry criteria.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Melanoma
Intervention  ICMJE
  • Drug: GSK 2132231A
    IM solution, a course of 13 injections administered over 27 months
  • Drug: Placebo
    IM solution, a course of 13 injections administered over 27 months
Study Arms  ICMJE
  • Experimental: MAGE-A3 Group
    Patients who received up to 13 doses of recMAGE-A3 + AS15 ASCI. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of ASCI product at 3-week intervals, followed by 8 doses of ASCI product at 12-week intervals.
    Intervention: Drug: GSK 2132231A
  • Placebo Comparator: Placebo Group
    Patients who received up to 13 doses of placebo. Study products were administered as intramuscular (IM) injections in the deltoid or the lateral region of the thigh (not in anatomical regions where lymph nodes had been excised): 5 doses of placebo at 3-week intervals, followed by 8 doses of placebo at 12-week intervals.
    Intervention: Drug: Placebo
Publications * Dreno B, Thompson JF, Smithers BM, Santinami M, Jouary T, Gutzmer R, Levchenko E, Rutkowski P, Grob JJ, Korovin S, Drucis K, Grange F, Machet L, Hersey P, Krajsova I, Testori A, Conry R, Guillot B, Kruit WHJ, Demidov L, Thompson JA, Bondarenko I, Jaroszek J, Puig S, Cinat G, Hauschild A, Goeman JJ, van Houwelingen HC, Ulloa-Montoya F, Callegaro A, Dizier B, Spiessens B, Debois M, Brichard VG, Louahed J, Therasse P, Debruyne C, Kirkwood JM. MAGE-A3 immunotherapeutic as adjuvant therapy for patients with resected, MAGE-A3-positive, stage III melanoma (DERMA): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Jul;19(7):916-929. doi: 10.1016/S1470-2045(18)30254-7. Epub 2018 Jun 13.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 19, 2013)
1351
Original Estimated Enrollment  ICMJE
 (submitted: November 21, 2008)
1300
Actual Study Completion Date  ICMJE January 27, 2016
Actual Primary Completion Date January 27, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Written informed consent signed.
  • Male or female patient with histologically proven stage IIIB or IIIC cutaneous melanoma presenting with macroscopic lymph node involvement suitable for surgery.
  • The patient must have been surgically rendered free of disease before the randomization.
  • Patient is ≥ 18 years old at the time of signing the informed consent form.
  • The patient's lymph node tumor shows expression of the MAGE-A3 gene.
  • The patient has fully recovered from surgery.
  • ECOG performance status of 0 or 1 at the time of randomization.
  • The patient must have adequate organ functions as assessed by standard laboratory criteria.
  • If the patient is female, she must be of non-childbearing potential, or practice adequate contraception.
  • In the opinion of the investigator, the patient can and will comply with all the requirements of the protocol.

Exclusion Criteria:

  • The patient suffers from a mucosal or ocular melanoma.
  • The patient has or has had any history of in-transit metastases
  • The patient has been treated or is scheduled to be treated with an adjuvant anticancer therapy after the surgery that qualifies the patient for inclusion in the present trial.
  • The patient requires concomitant chronic treatment with systemic corticosteroids or any other immunosuppressive agents.
  • Use of any investigational or non-registered product (drug or vaccine) other than the study treatment.
  • The patient has a history of autoimmune disease.
  • The patient has a family history of congenital or hereditary immunodeficiency.
  • The patient is known to be positive for Human Immunodeficiency Virus (HIV) or has another confirmed or suspected immunosuppressive or immunodeficient condition.
  • History of allergic disease or reactions likely to be exacerbated by any component of the treatments.
  • The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
  • The patient has concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
  • The patient has previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers or carcinoma in situ of the cervix or effectively treated malignancy that has been in remission for over 5 years and is highly likely to have been cured.
  • The patient has an uncontrolled bleeding disorder.
  • For female patients: the patient is pregnant or lactating.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   Czechia,   Estonia,   France,   Germany,   Greece,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   New Zealand,   Norway,   Poland,   Romania,   Russian Federation,   Serbia,   Spain,   Sweden,   Switzerland,   Taiwan,   Ukraine,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT00796445
Other Study ID Numbers  ICMJE 111482
2008-002447-16 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: https://clinicalstudydatarequest.com
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP