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

Melanoma (Skin) Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00086866
• Other study ID #: EORTC-16032-18031
• Secondary ID: EORTC-18031EORTC
• Status: Active, not recruiting
• Phase: Phase 2
• First received: July 8, 2004
• Last updated: February 9, 2015
• Start date: May 2004

Study information

• Verified date: February 2015
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 165
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Biological:
• D1/3-MAGE-3-His fusion protein

• SB-AS02B adjuvant

• SB-AS15 adjuvant

Locations

Country	Name	City	State
Belgium	Hopital Universitaire Erasme	Brussels
Belgium	Institut Jules Bordet	Brussels
France	Clinique Sainte-Marguerite	Hyeres
France	Centre Hospitalier Regional et Universitaire de Lille	Lille
France	Hopital St. Eloi	Montpellier
France	CHR Hotel Dieu	Nantes
France	Institut Curie Hopital	Paris
France	Institut Gustave Roussy	Villejuif
Germany	Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin	Berlin
Germany	Klinikum der Stadt Mannheim	Mannheim
Germany	Universitaets - Kinderklinik Wuerzburg	Wuerzburg
Italy	Centro di Riferimento Oncologico - Aviano	Aviano
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori	Naples
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Universita di Siena	Siena
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Daniel Den Hoed Cancer Center at Erasmus Medical Center	Rotterdam
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	Christie Hospital NHS Trust	Manchester	England

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

References & Publications (2)

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

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 Cl

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate (complete response and partial response) as assessed by RECIST criteria			No
Primary	Vaccine-related toxicity as assessed by CTCAE v3			Yes
Secondary	Rate of stabilization as assessed by RECIST criteria			No
Secondary	Rate of mixed response as assessed by RECIST criteria			No
Secondary	Rate of immune response			No
Secondary	Progression-free survival			No