Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Alternate Title

Vaccine Therapy With or Without Immune Adjuvant in Treating Patients With Cancer That Has Not Responded to Previous Treatment

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Closed Over 18 EORTC-18972-13971/LUD97-002

Objectives

I.  Determine the maximum tolerated dose of MAGE-3 plus immunological adjuvant 
SB AS-2 in HLA class I patients with MAGE-3 positive refractory malignant 
tumors.

II.  Determine the safety and toxicity of this treatment in these patients.

III.  Evaluate this treatment regimen in terms of immune response and tumor 
response in this patient population.
 

Entry Criteria

Disease Characteristics:

Histologically proven locally advanced or metastatic malignancies refractory
to existing therapy or for which no standard therapy exists
 Cutaneous melanoma
  Stage III or IV
 Non-small cell lung cancer (NSCLC)
  Stage IIIB or IV
 Head and neck carcinoma
  Stage IV with high risk of recurrence (Tany-N3, T4-N1, T4-N2) 
 Esophageal carcinoma
  Stage IIB, III, or IV
 Bladder carcinoma
 Stage III or IV
 
Measurable disease

Expression of at least one of the class I HLA alleles:
 HLA-A1
 HLA-A2
 HLA-B44

Tumor expression of gene MAGE-3 in at least 1 tumor sample
 
No brain metastases

Prior/Concurrent Therapy:

Biologic therapy:
 At least 4 weeks since prior immunotherapy
 No other concurrent immunotherapy
 At least 8 weeks since other prior tumor vaccines
 No prior MAGE-3 based vaccines

Chemotherapy:
 At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or
  mitomycin)
 No concurrent chemotherapy

Endocrine therapy:
 No concurrent nonsubstitutional hormonal therapy
 No concurrent corticosteriods

Radiotherapy:
 At least 4 weeks since prior radiotherapy
 No prior radiotherapy to the spleen
 Local radiotherapy to control symptoms allowed (therapy to all
  measurable/evaluable lesions excluded)

Surgery:
 Recovered from prior surgery
 No prior major organ transplantation
 No prior splenectomy
 Local surgery to control symptoms allowed (therapy to all
  measurable/evaluable lesions excluded)

Patient Characteristics:

Age:
 Over 18

Performance status:
 WHO 0-1

Life expectancy:
 Not specified

Hematopoietic:
 Granulocyte count at least 2,000/mm3
 Lymphocyte count at least 700/mm3
 Platelet count at least 100,000/mm3
 Hemoglobin at least 8 mg/dL
 PT and PTT normal
 No bleeding disorders

Hepatic:
 Bilirubin no greater than 2.0 mg/dL
 AST and ALT no greater than 2 times upper limit of normal (ULN) (no greater
  than 5 times ULN if liver metastases)
 Negative hepatitis B antigens (positive antibodies allowed)
 Hepatitis C negative

Renal:
 Creatinine no greater than 2.0 mg/dL

Cardiovascular:
 No uncontrolled congestive heart failure or hypertension
 No unstable coronary artery disease
 No serious arrhythmias

Pulmonary:
 No major respiratory disease

Other:
 HIV negative
 No other serious acute or chronic illnesses (e.g., active infections
  requiring antibiotics)
 No other active malignancies except basal cell skin cancer
 No other conditions requiring concurrent medications not allowed in study
 No autoimmune diseases (e.g., inflammatory bowel disease or multiple
  sclerosis)
 Vitiligo allowed
 No organic brain syndrome or significant psychiatric abnormality precluding
  study
 Not pregnant or nursing
 Negative pregnancy test
 Fertile patients must use effective contraception during and for 3 months
  after study

Expected Enrollment

A total of 41 patients will be accrued for this study.

Outline

This is a dose escalation study of MAGE-3. Patients are stratified according 
to HLA type (HLA-A1 positive vs HLA-A1 negative, HLA-A2 and/or HLA-B44 
positive), and melanoma diagnosis (yes vs no).

The first 5 patients receive MAGE-3 intramuscularly (IM) alone and the 
remaining patients receive MAGE-3 with immunological adjuvant SB AS-2 (SB 
AS-2) IM. Treatment repeats every 3 weeks for 4 courses in the absence of 
symptomatic and/or life threatening disease progression or unacceptable 
toxicity. Patients achieving tumor response or stable disease receive 
additional treatment every 6 weeks for 2 courses.

Cohorts of 6-12 patients receive escalating doses of MAGE-3 until the maximum 
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding 
that at which 2 of 6 patients experience dose limiting toxicity.

Patients are followed every 3 months until disease progression.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Gerrit Stoter, MD, PhD, Protocol chair		Ph: 31-10-439-1331 Email: g.stoter@erasmusmc.nl