Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed With Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00086866
First received: July 8, 2004
Last updated: September 20, 2013
Last verified: September 2013
  Purpose

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells.

PURPOSE: This randomized phase II trial is studying two different regimens of vaccine therapy and comparing them to see how well they work in treating patients with stage III or stage IV melanoma that cannot be removed with surgery.


Condition Intervention Phase
Melanoma (Skin)
Biological: D1/3-MAGE-3-His fusion protein
Biological: SB-AS02B adjuvant
Biological: SB-AS15 adjuvant
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized, Open Phase II Study of Immunization With the Recombinant MAGE-3 Protein Combined With Adjuvant AS02B or AS15 in Patients With Unresectable and Progressive Metastatic Cutaneous Melanoma

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Response rate (complete response and partial response) as assessed by RECIST criteria [ Designated as safety issue: No ]
  • Vaccine-related toxicity as assessed by CTCAE v3 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Rate of stabilization as assessed by RECIST criteria [ Designated as safety issue: No ]
  • Rate of mixed response as assessed by RECIST criteria [ Designated as safety issue: No ]
  • Rate of immune response [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]

Enrollment: 165
Study Start Date: May 2004
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Compare the objective response rate (complete and partial response) in patients with unresectable stage III or stage IV M1a cutaneous melanoma immunized with vaccine comprising D1/3-MAGE-3-His fusion protein and SB-AS02B adjuvant vs SB-AS15 adjuvant.
  • Compare the activity of SB-AS02B adjuvant vs SB-AS15 adjuvant, in terms of maximizing the antigenicity of MAGE-3, in patients treated with these regimens.
  • Compare the rate of grade 3/4 vaccine-related toxicity in patients treated with these regimens.

Secondary

  • Compare progression-free survival in patients treated with these regimens.

OUTLINE: This is a randomized, open label, parallell-group, multicenter study. Patients are stratified according to disease stage (III in transit vs other stage III vs IV), presence of lesion ≥ 20 mm (yes vs no), and participating center. Patients are randomized to 1 of 2 treatment arms.

  • Induction therapy

    • Arm I: Patients receive immunization comprising D1/3-MAGE-3-His fusion protein and SB-AS02B adjuvant intramuscularly (IM) once weekly on weeks 1, 3, 5, 7, 9, and 11.
    • Arm II: Patients receive immunization comprising D1/3-MAGE-3-His fusion protein SB-AS15 adjuvant IM once weekly on weeks 1, 3, 5, 7, 9, and 11.

Patients achieving a clinical complete response (CR), partial response (PR), stable disease (SD), or slow progressive disease (SPD) proceed to maintenance therapy.

  • Maintenance therapy: Patients in both arms receive immunization (according to their randomized arm) once weekly on weeks 15, 18, 21, 24, 27, 30, 34, 40, 46, and 52.

Patients maintaining a CR, PR, or SD proceed to long-term treatment.

  • Long-term treatment: Beginning 3 months after completion of maintenance therapy, patients in both arms receive immunization (according to their randomized arm) once every 3 months for 4 courses and then once every 6 months for 4 courses.

Treatment continues in both arms in the absence of disease progression that does not correspond to SPD status, unacceptable toxicity, or the diagnosis of an autoimmune disease.

Patients are followed every 12 weeks.

PROJECTED ACCRUAL: A total of 68 patients (34 patients per treatment arm) will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed cutaneous melanoma

    • Unresectable stage III OR stage IV M1a disease
  • Documented progressive disease within the past 12 weeks
  • Measurable disease
  • Skin, soft tissue, or lymph node metastasis allowed provided the disease is not amenable to curative treatment with surgery
  • Tumor must express the MAGE-3 gene by reverse transcription polymerase chain reaction analysis (more than 1% of the positive MAGE-3 control included in the assay)
  • No visceral metastases within the past 56 days by imaging

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Hemoglobin ≥ lower limit of normal (LLN)
  • WBC ≥ LLN
  • Lymphocyte count ≥ LLN
  • Platelet count ≥ LLN
  • No bleeding disorders

Hepatic

  • Bilirubin ≤ upper limit of normal (ULN)
  • Lactic dehydrogenase ≤ ULN
  • AST and ALT ≤ 2 times ULN
  • PT and aPTT normal
  • Hepatitis B surface antigen negative (antibody test may be positive)
  • Hepatitis C antibody negative

Renal

  • Creatinine ≤ ULN

Cardiovascular

  • No clinically significant heart disease (CTC grade III or IV)

Immunologic

  • No autoimmune disease (vitiligo allowed)
  • No anti-nuclear antibody titer ≥ 1/320 OR equal to 1/160 AND auto-antibodies directed against specific auto-antigens
  • No immunodeficiency
  • No active infection requiring antibiotic therapy
  • HIV negative

Other

  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study participation
  • No other malignancy within the past 5 years except surgically cured basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No other serious acute or chronic illness requiring concurrent medications
  • No psychological, familial, sociological, or geographical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • More than 8 weeks since prior adjuvant vaccine therapy
  • No prior vaccine therapy containing a MAGE-3 antigen
  • No prior vaccine therapy for metastatic melanoma
  • No concurrent immunomodulating agents (e.g., BCG)

Chemotherapy

  • No prior systemic chemotherapy
  • No concurrent chemotherapy

Endocrine therapy

  • No concurrent corticosteroids

    • Concurrent prednisone or equivalent allowed provided the dose is ≤ 40 mg/day and treatment duration is for no more than 3 weeks
    • Concurrent inhaled and topical steroids are allowed

Radiotherapy

  • No prior radiotherapy to the spleen
  • No concurrent radiotherapy to > 20% of all existing lesions (i.e., target lesions, non-target lesions, and nonmeasurable lesions)

    • Concurrent local low-dose (≤ 20 Grays) radiotherapy allowed

Surgery

  • Recovered from prior surgery or biopsy
  • No prior organ allograft
  • No prior splenectomy
  • Concurrent surgery to a limited number of lesions allowed for patients with a complete response, partial response, or stable disease after at least 3 courses of study therapy

Other

  • No prior systemic anticancer therapy
  • More than 4 weeks since prior isolated limb perfusion therapy
  • No other concurrent anticancer therapy
  • No other concurrent immunosuppressive agents
  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: NCT00086866

Locations
Belgium
Hopital Universitaire Erasme
Brussels, Belgium, 1070
Institut Jules Bordet
Brussels, Belgium, 1000
France
Clinique Sainte-Marguerite
Hyeres, France, 83400
Centre Hospitalier Regional et Universitaire de Lille
Lille, France, 59037
Hopital St. Eloi
Montpellier, France, 34295
CHR Hotel Dieu
Nantes, France, 44093
Institut Curie Hopital
Paris, France, 75248
Institut Gustave Roussy
Villejuif, France, F-94805
Germany
Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
Berlin, Germany, D-12200
Klinikum der Stadt Mannheim
Mannheim, Germany, D-68135
Universitaets - Kinderklinik Wuerzburg
Wuerzburg, Germany, D-97080
Italy
Centro di Riferimento Oncologico - Aviano
Aviano, Italy, 33081
Istituto Nazionale per lo Studio e la Cura dei Tumori
Naples, Italy, 80131
Azienda Ospedaliera di Padova
Padova, Italy, 35128
Universita di Siena
Siena, Italy, 53100
Netherlands
Leiden University Medical Center
Leiden, Netherlands, 2300 RC
Daniel Den Hoed Cancer Center at Erasmus Medical Center
Rotterdam, Netherlands, 3008 AE
Spain
Hospital Clinic de Barcelona
Barcelona, Spain, 08036
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
United Kingdom
Saint Bartholomew's Hospital
London, England, United Kingdom, EC1A 7BE
Christie Hospital NHS Trust
Manchester, England, United Kingdom, M20 4BX
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Willem H. J. Kruit, MD, PhD Daniel Den Hoed Cancer Center at Erasmus Medical Center
Study Chair: Cornelis J. A. Punt, MD, PhD Universitair Medisch Centrum St. Radboud - Nijmegen
  More Information

Additional Information:
Publications:
Kruit WH, Suciu S, Dreno B, et al.: Immunization with recombinant MAGE-A3 protein combined with adjuvant systems AS15 or AS02B in patients with unresectable and progressive metastatic cutaneous melanoma: A randomized open-label phase II study of the EORTC Melanoma Group (16032- 18031). [Abstract] J Clin Oncol 26 (Suppl 15): A-9065, 2008.
Louahed J, Gruselle O, Gaulis S, et al.: Expression of defined genes identified by pretreatment tumor profiling: association with clinical responses to the GSK MAGE- A3 immunotherapeutic in metastatic melanoma patients (EORTC 16032-18031). [Abstract] J Clin Oncol 26 (Suppl 15): A-9045, 2008.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00086866     History of Changes
Other Study ID Numbers: EORTC-16032-18031, EORTC-18031, EORTC-16032, GSK-249553/008, 2004-001937-40
Study First Received: July 8, 2004
Last Updated: September 20, 2013
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
stage III melanoma
stage IV melanoma
recurrent melanoma

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 July 29, 2014