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
18 Years
N/A
Both
Melanoma (Skin)
Trial Information
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
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Response rate (complete response and partial response) as assessed by RECIST criteria
Safety Issue:
No
Principal Investigator
Willem H. J. Kruit, MD, PhD
Investigator Affiliation:
Daniel Den Hoed Cancer Center at Erasmus Medical Center
Authority:
United States: Federal Government
Study ID:
CDR0000371707
NCT ID:
NCT00086866
Start Date:
May 2004
Completion Date:
Related Keywords:
- Melanoma (Skin)
- stage III melanoma
- stage IV melanoma
- recurrent melanoma
- Melanoma
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