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

• ClinicalTrials.gov Identifier: NCT00613509
• Recruitment Status: Terminated
• First Posted: February 13, 2008
• Results First Posted: December 17, 2010
• Last Update Posted: April 14, 2016
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Melanoma; Cancer	Biological: ALVAC(2) Melanoma multi-antigen therapeutic vaccine; Biological: Intron A, Interferon alpha -2b	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of a Multi-Antigen Therapeutic Vaccine in Patients With Metastatic Melanoma
• Study Start Date: June 2008
• Actual Primary Completion Date: April 2010
• Actual Study Completion Date: June 2010

Arms and Interventions

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 Name: Intron-A®: IFN-α2b

Outcome Measures

Primary Outcome Measures :

1. Summary of Disease Progression in Study Participants, Intent-to-treat Population [ Time Frame: Day 0 up to 35 weeks post 1st vaccination or treatment ]
   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).
2. 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 ]
   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 :

1. 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 ]
   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.
2. Best Overall Objective Response in the Intent-to-treat Population [ Time Frame: Day 0 to 32 weeks post 1st vaccination or treatment ]
   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.
3. 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 ]
   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.
4. 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 ]

   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:

1. 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 ]
   The vaccine-induced increase of CD8 T-Cell positive response by antigen post-vaccination during the observation period compared to the screening values.
2. 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 ]
   The Vaccine-induced increase of CD4 T-Cell positive response by antigen post-vaccination during the observation period compared to the screening values.
3. 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 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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:

Related Info 

Related Info 

Related Info 

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT00613509
• Other Study ID Numbers: MEL11
• First Posted: February 13, 2008
• Results First Posted: December 17, 2010
• Last Update Posted: April 14, 2016
• Last Verified: April 2016

Keywords provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):

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; Interferons; Interferon-alpha; Vaccines; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Immunologic Factors; Physiological Effects of Drugs