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

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

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.

Study Overview

• Status: Terminated
• Conditions: Melanoma; Cancer
• Intervention / Treatment: Biological: ALVAC(2) Melanoma multi-antigen therapeutic vaccine; Biological: Intron A, Interferon alpha -2b

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
    • London, Ontario, Canada
    • Toronto, Ontario, Canada, M4N 3M5
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
  • California
    • Los Angeles, California, United States, 90024
  • Colorado
    • Aurora, Colorado, United States, 80045
  • Georgia
    • Atlanta, Georgia, United States, 30322
  • Illinois
    • Chicago, Illinois, United States, 60611
  • Missouri
    • St Louis, Missouri, United States, 63110
  • Nebraska
    • Omaha, Nebraska, United States, 68198
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
  • Oregon
    • Portland, Oregon, United States, 97213
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
    • Pittsburgh, Pennsylvania, United States, 15232
  • South Carolina
    • Greenville, South Carolina, United States, 29605
  • Texas
    • Dallas, Texas, United States, 75246
    • San Antonio, Texas, United States, 78229
  • Wisconsin
    • Madison, Wisconsin, United States, 53792

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: Intron-A®: IFN-α2b

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary of Disease Progression in Study Participants, Intent-to-treat Population	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).	Day 0 up to 35 weeks post 1st vaccination or treatment
Progression-Free Survival Time by Response Evaluation Criteria in Solid Tumor (RECIST) Criteria in the Intent-to-treat Population	Progression-Free Survival was assessed by the Response Evaluation Criteria in Solid Tumor criteria from the computed tomography (CT) scans, as per-protocol	Day 0 - up to 35 weeks post 1st vaccination or treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Objective Response as Number of Participants Responding in the Intent-to-treat Population	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.	Day 0 to 32 weeks post 1st vaccination or treatment
Best Overall Objective Response in the Intent-to-treat Population	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.	Day 0 to 32 weeks post 1st vaccination or treatment
Best Overall Objective Response as Mean Duration of Response (Weeks) in the Intent-to-treat Population	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.	Day 0 to 32 weeks post 1st vaccination or treatment
Number of Participants Reporting a Grade 3 or Grade 4 Adverse Events by Preferred Term	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.	Day 0 to 12 months post last vaccination

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Vaccine-Induced Increase of CD8 T-Cell Positive Response by Antigen	The vaccine-induced increase of CD8 T-Cell positive response by antigen post-vaccination during the observation period compared to the screening values.	Day 0 to 32 weeks post 1st vaccination
Number of Participants With a Vaccine-Induced Increase of CD4 T-Cell Positive Response by Antigen	The Vaccine-induced increase of CD4 T-Cell positive response by antigen post-vaccination during the observation period compared to the screening values.	Day 0 to 32 weeks post 1st vaccination
Summary of Cellular Immune Response to the Vaccination or Treatment (Percent Regulatory T-Cells Responses)	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.	Day 0 to 32 weeks post 1st vaccination or treatment

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

Helpful Links

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Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: January 16, 2008
• First Submitted That Met QC Criteria: January 30, 2008
• First Posted (Estimate): February 13, 2008

Study Record Updates

• Last Update Posted (Estimate): April 14, 2016
• Last Update Submitted That Met QC Criteria: April 12, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Melanoma, Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Vaccines
• Other Study ID Numbers: MEL11