Study of a Multi-Antigen Therapeutic Vaccine in Patients With Metastatic Melanoma

This study has been terminated.
(No safety concerns, the study was terminated due to slow enrollment. All enrolled patients were followed per protocol.)
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00613509
First received: January 16, 2008
Last updated: January 20, 2014
Last verified: January 2014
  Purpose

Primary objective:

To evaluate the clinical activity of the vaccine regimen, as indicated by progression-free survival versus the clinical activity of the reference treatment.

Secondary objectives:

Safety: To describe the safety profile in both treatment groups.

Efficacy: To determine the objective clinical responses of patients in both treatment groups: complete response and partial response.


Condition Intervention Phase
Melanoma
Cancer
Biological: ALVAC(2) Melanoma multi-antigen therapeutic vaccine
Biological: Intron A, Interferon alpha -2b
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of a Multi-Antigen Therapeutic Vaccine in Patients With Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Summary of Disease Progression in Study Participants, Intent-to-treat Population [ Time Frame: Day 0 up to 35 weeks post 1st vaccination or treatment ] [ Designated as safety issue: No ]
    Number of evaluable study participants who had died or experienced objective disease progression (no clinical objective response to treatment as evaluated by computed tomography [CT] scans or physical examination).

  • Progression-Free Survival Time by Response Evaluation Criteria in Solid Tumor (RECIST) Criteria in the Intent-to-treat Population [ Time Frame: Day 0 - up to 35 weeks post 1st vaccination or treatment ] [ Designated as safety issue: No ]
    Progression-Free Survival was assessed by the Response Evaluation Criteria in Solid Tumor criteria from the computed tomography (CT) scans, as per-protocol


Secondary Outcome Measures:
  • Best Overall Objective Response as Number of Participants Responding in the Intent-to-treat Population [ Time Frame: Day 0 to 32 weeks post 1st vaccination or treatment ] [ Designated as safety issue: No ]
    Objective response rate (ORR) is the sum of complete response (CR) and partial response (PR) Complete response = Disappearance of all target lesions. Partial response = At least a 30% decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter.

  • Best Overall Objective Response in the Intent-to-treat Population [ Time Frame: Day 0 to 32 weeks post 1st vaccination or treatment ] [ Designated as safety issue: No ]
    Objective response rate (ORR) is the sum of complete response (CR) and partial response (PR) Complete response = Disappearance of all target lesions. Partial response = At least a 30% decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter.

  • Best Overall Objective Response as Mean Duration of Response (Weeks) in the Intent-to-treat Population [ Time Frame: Day 0 to 32 weeks post 1st vaccination or treatment ] [ Designated as safety issue: No ]
    Objective response rate (ORR) is the sum of complete response (CR) and partial response (PR) Complete response = Disappearance of all target lesions. Partial response = At least a 30% decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter.

  • Number of Participants Reporting a Grade 3 or Grade 4 Adverse Events by Preferred Term [ Time Frame: Day 0 to 12 months post last vaccination ] [ Designated as safety issue: No ]

    Common Terminology Criteria for Adverse Events (CTCAE) definitions:

    Grade 3 is a severe adverse event; Grade 4 is a life-threatening or disabling adverse event.



Other Outcome Measures:
  • Number of Participants With a Vaccine-Induced Increase of CD8 T-Cell Positive Response by Antigen [ Time Frame: Day 0 to 32 weeks post 1st vaccination ] [ Designated as safety issue: No ]
    The vaccine-induced increase of CD8 T-Cell positive response by antigen post-vaccination during the observation period compared to the screening values.

  • Number of Participants With a Vaccine-Induced Increase of CD4 T-Cell Positive Response by Antigen [ Time Frame: Day 0 to 32 weeks post 1st vaccination ] [ Designated as safety issue: No ]
    The Vaccine-induced increase of CD4 T-Cell positive response by antigen post-vaccination during the observation period compared to the screening values.

  • Summary of Cellular Immune Response to the Vaccination or Treatment (Percent Regulatory T-Cells Responses) [ Time Frame: Day 0 to 32 weeks post 1st vaccination or treatment ] [ Designated as safety issue: No ]
    The immunogenicity of the treatment regimens was assessed by regulatory T-cell responses as assessed primarily by the multi-parametric intracellular cytokine staining (ICS) assay.


Enrollment: 23
Study Start Date: June 2008
Study Completion Date: June 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Study Group 1: ALVAC melanoma vaccine
Participants will receive a multi-antigen of modified canarypox virus (ALVAC[2]) melanoma vaccine and granulocyte macrophage colony stimulating factor (GM-CSF) every 3 weeks, followed by 4 weeks of high-dose interferon alpha-2b 5 times per week.
Biological: ALVAC(2) Melanoma multi-antigen therapeutic vaccine
0.5 mL, 2 cycles
Active Comparator: Study Group 2: Interferon alpha-2b
Participants on 4 weeks of high-dose interferon alpha-2b 5 times per week. Participants who showed disease progression after Cycle 1 will be permitted to cross over to Group 1 treatment.
Biological: Intron A, Interferon alpha -2b
0.5 mL, 5 times per week for 4 weeks
Other Name: Intron-A®: IFN-α2b

Detailed Description:

Eligible participants will be randomized to receive either a vaccine treatment consisting of a series of multi-antigen melanoma vaccine and GM-CSF injections, followed by high-dose IFN-α2b or only the high-dose IFN-α2b.

  Eligibility

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

Inclusion Criteria :

  • A pathologically confirmed diagnosis of malignant melanoma with at least one measurable metastatic lesion with a minimum lesion size of 20 mm, based on radiological assessment (or 10 mm if assessed by spiral computed tomography [CT] scan ) as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Stages IIIc, IVa, or IVb only, according to the American Joint Committee on Cancer (AJCC) staging system for melanoma). Cutaneous metastasis (assessed by physical examination) must be at least 10 mm. CT scan or magnetic resonance imaging (MRI) is required to rule out brain metastases.
  • Patients who received prior treatment for their metastatic disease must have objective evidence of disease progression.
  • Aged ≥ 18 years on the day of inclusion
  • IRB-approved informed consent form signed
  • Able to attend all scheduled visits and to comply with all trial procedures
  • For a woman, inability to bear a child or negative serum pregnancy test
  • For a woman of child-bearing potential, using an effective method of contraception or abstinence during the study and at least 4 weeks after the last study treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a life expectancy of at least 6 months.
  • Adequate hematologic, hepatic, and renal function (at pre-defined laboratory values).
  • Fully recovered from surgery, if applicable.

Exclusion Criteria :

  • Receipt of two or more previous therapies for metastatic melanoma.
  • Receipt of chemotherapy or another therapy for metastatic melanoma within the last four weeks
  • Receipt of adjuvant interferon therapy within the last six months
  • Concurrent receipt of radiotherapy for the metastatic disease, unless for palliative purposes
  • Participation in another clinical trial within the four weeks preceding the first trial treatment
  • Planned participation in another clinical trial during the present trial period
  • Known Human Immunodeficiency Virus (HIV) infection or hepatitis B (Ag HBs) or hepatitis C seropositivity
  • Presence of active autoimmune disease (excluding vitiligo)
  • Systemic hypersensitivity to bovine products or to any of the vaccine components, including egg products or Neomycin (used to prepare the vaccine), or history of a life-threatening reaction to granulocyte-macrophage colony stimulating factor (GM-CSF) or interferon (IFN)-α2b
  • Current alcohol or drug addiction that may interfere with the ability to comply with trial procedures
  • Significant co-morbid medical conditions, including pre-existing renal disease, cirrhosis, or major depression, which in the estimation of the investigator would preclude safe participation in the study or the accurate interpretation of data.
  • A calculated glomerular filtration rate (GFR) <60 mL/min (based on the Cockroft-Gault formula).
  • Previous receipt of a modified canarypox virus (ALVAC)-based vaccine.
  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: NCT00613509

Locations
United States, Arizona
Tucson, Arizona, United States, 85724
United States, California
Los Angeles, California, United States, 90024
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Georgia
Atlanta, Georgia, United States, 30322
United States, Illinois
Chicago, Illinois, United States, 60611
United States, Missouri
St Louis, Missouri, United States, 63110
United States, Nebraska
Omaha, Nebraska, United States, 68198
United States, New Hampshire
Lebanon, New Hampshire, United States, 03756
United States, Oregon
Portland, Oregon, United States, 97213
United States, Pennsylvania
Bethlehem, Pennsylvania, United States, 18015
Pittsburgh, Pennsylvania, United States, 15232
United States, South Carolina
Greenville, South Carolina, United States, 29605
United States, Texas
Dallas, Texas, United States, 75246
San Antonio, Texas, United States, 78229
United States, Wisconsin
Madison, Wisconsin, United States, 53792
Canada, Ontario
Hamilton, Ontario, Canada, L8V 5C2
London, Ontario, Canada
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Montreal, Quebec, Canada, H3A 1A1
Sponsors and Collaborators
Sanofi Pasteur, a Sanofi Company
Investigators
Study Director: Medical Director Sanofi Pasteur Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00613509     History of Changes
Other Study ID Numbers: MEL11
Study First Received: January 16, 2008
Results First Received: September 14, 2010
Last Updated: January 20, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Sanofi:
Melanoma, Cancer

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
Interferon-alpha
Interferons
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 28, 2014