Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed With Surgery
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
OBJECTIVES:
Primary
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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.
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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.
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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.
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Induction therapy
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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.
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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.
Study Design
Outcome Measures
Primary Outcome Measures
- Response rate (complete response and partial response) as assessed by RECIST criteria []
- Vaccine-related toxicity as assessed by CTCAE v3 []
Secondary Outcome Measures
- Rate of stabilization as assessed by RECIST criteria []
- Rate of mixed response as assessed by RECIST criteria []
- Rate of immune response []
- Progression-free survival []
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
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Histologically confirmed cutaneous melanoma
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Unresectable stage III OR stage IV M1a disease
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Documented progressive disease within the past 12 weeks
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Measurable disease
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Skin, soft tissue, or lymph node metastasis allowed provided the disease is not amenable to curative treatment with surgery
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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)
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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
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Hemoglobin ≥ lower limit of normal (LLN)
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WBC ≥ LLN
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Lymphocyte count ≥ LLN
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Platelet count ≥ LLN
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No bleeding disorders
Hepatic
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Bilirubin ≤ upper limit of normal (ULN)
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Lactic dehydrogenase ≤ ULN
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AST and ALT ≤ 2 times ULN
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PT and aPTT normal
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Hepatitis B surface antigen negative (antibody test may be positive)
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Hepatitis C antibody negative
Renal
- Creatinine ≤ ULN
Cardiovascular
- No clinically significant heart disease (CTC grade III or IV)
Immunologic
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No autoimmune disease (vitiligo allowed)
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No anti-nuclear antibody titer ≥ 1/320 OR equal to 1/160 AND auto-antibodies directed against specific auto-antigens
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No immunodeficiency
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No active infection requiring antibiotic therapy
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HIV negative
Other
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Not pregnant
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Negative pregnancy test
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Fertile patients must use effective contraception during and for 3 months after study participation
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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
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No other serious acute or chronic illness requiring concurrent medications
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No psychological, familial, sociological, or geographical condition that would preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
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More than 8 weeks since prior adjuvant vaccine therapy
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No prior vaccine therapy containing a MAGE-3 antigen
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No prior vaccine therapy for metastatic melanoma
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No concurrent immunomodulating agents (e.g., BCG)
Chemotherapy
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No prior systemic chemotherapy
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No concurrent chemotherapy
Endocrine therapy
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No concurrent corticosteroids
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Concurrent prednisone or equivalent allowed provided the dose is ≤ 40 mg/day and treatment duration is for no more than 3 weeks
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Concurrent inhaled and topical steroids are allowed
Radiotherapy
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No prior radiotherapy to the spleen
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No concurrent radiotherapy to > 20% of all existing lesions (i.e., target lesions, non-target lesions, and nonmeasurable lesions)
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Concurrent local low-dose (≤ 20 Grays) radiotherapy allowed
Surgery
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Recovered from prior surgery or biopsy
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No prior organ allograft
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No prior splenectomy
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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
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No prior systemic anticancer therapy
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More than 4 weeks since prior isolated limb perfusion therapy
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No other concurrent anticancer therapy
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No other concurrent immunosuppressive agents
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Institut Jules Bordet | Brussels | Belgium | 1000 | |
| 2 | Hopital Universitaire Erasme | Brussels | Belgium | 1070 | |
| 3 | Clinique Sainte-Marguerite | Hyeres | France | 83400 | |
| 4 | Centre Hospitalier Regional et Universitaire de Lille | Lille | France | 59037 | |
| 5 | Hopital St. Eloi | Montpellier | France | 34295 | |
| 6 | CHR Hotel Dieu | Nantes | France | 44093 | |
| 7 | Institut Curie Hopital | Paris | France | 75248 | |
| 8 | Institut Gustave Roussy | Villejuif | France | F-94805 | |
| 9 | Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin | Berlin | Germany | D-12200 | |
| 10 | Klinikum der Stadt Mannheim | Mannheim | Germany | D-68135 | |
| 11 | Universitaets - Kinderklinik Wuerzburg | Wuerzburg | Germany | D-97080 | |
| 12 | Centro di Riferimento Oncologico - Aviano | Aviano | Italy | 33081 | |
| 13 | Istituto Nazionale per lo Studio e la Cura dei Tumori | Naples | Italy | 80131 | |
| 14 | Azienda Ospedaliera di Padova | Padova | Italy | 35128 | |
| 15 | Universita di Siena | Siena | Italy | 53100 | |
| 16 | Leiden University Medical Center | Leiden | Netherlands | 2300 RC | |
| 17 | Daniel Den Hoed Cancer Center at Erasmus Medical Center | Rotterdam | Netherlands | 3008 AE | |
| 18 | Hospital Clinic de Barcelona | Barcelona | Spain | 08036 | |
| 19 | Hospital Universitario 12 de Octubre | Madrid | Spain | 28041 | |
| 20 | Saint Bartholomew's Hospital | London | England | United Kingdom | EC1A 7BE |
| 21 | 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
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EORTC-16032-18031
- EORTC-18031
- EORTC-16032
- GSK-249553/008
- 2004-001937-40