Active Specific Intranodal Immunotherapy of Recombinant Vaccinia Virus in Locally Advanced to Metastatic Melanoma

NCT00116597 | Completed Phase 1 DMC

• 2 other identifiers: GT1999017/05.050SNF grant NPF 37 4037-55151
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess intranodal immunotherapy in locally advanced to metastatic melanoma patients (American Joint Committee on Cancer \[AJCC\] stages IIb to IV). For this, the investigators capitalize on their previous melanoma clinical trial (published by Zajac P et al in Human Gene Ther 2003) and take advantage of a proprietary recombinant vaccinia virus (replication inactivated) expressing 5 minigenes: 3 melanoma associated antigens and 2 costimulatory molecules. Immunization with the recombinant vaccinia virus is followed by 3 boosts with soluble, synthetic melanoma associated antigens. The patients are immunized intranodally (groin lymph node) under ultrasonographic guidance in an outpatient clinic. The protocol foresees 2 cycles of immunotherapy for alternate weeks and lasts 15 weeks.

Conditions

Melanoma

Keywords

Active Specific Immunotherapy; Intranodal; Cancer; Melanoma stages IIb to IV; Gene Therapy; Recombinant Vaccinia virus; HLA-A2; Mart-1/Melan-A, Gp-100, tyrosinase; Clinical Trial; Phase I/II

Outcome Measures

Primary Outcomes (3)

• Safety evaluation

• Clinical response

• Immune response assessment

Secondary Outcomes (2)

• Survival (disease-free survival [DFS], overall survival [OS])

• Dose adaptation

Interventions

Intranodal immunization with a recombinant vaccinia virus expressing 5 transgenes GENETIC

Intranodal booster immunizations with synthetic melanoma associated epitopes BIOLOGICAL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients older than 18 years
• Histologically proven melanoma in AJCC stages IIb to IV
• Resected, recurrent or disseminated disease
• HLA-A2.1 MHC phenotype
• Karnofsky performance status equal or higher than 70%

You may not qualify if:

• Patients younger than 18 years
• Pregnancy or inability to perform anticonception
• MHC phenotype other than HLA-A2.1
• Other concurrent malignant disease
• Estimated life expectancy of less than 6 months
• Allergic skin diseases, including eczema, psoriasis and neurodermitis
• Fever or active infection of the respiratory system
• Concurrent severe cardiac or pulmonary disease (New York Heart Association \[NYHA\] III and IV)
• Significant impairment of liver or kidney function (bilirubin \> 30umol/l, GOT \>2.5xN, GPT \>2.5xN, alkaline phosphatase \>2.5xN, creatinine \>1.5xN adapted to the age)
• Impairment of the immune system (leucocyte counts \<3000/mm3 or granulocytes counts \<1500/mm3)
• Concurrent immunosuppressive therapy
• Preexisting severe anemia (hemoglobin lower than 80 g/l)
• Preexisting thrombocytopenia (platelet counts lower than 75,000/ul)
• Ongoing chemotherapy or chemotherapy completed less than 6 weeks before enrollment in the trial
• Any medical or psychiatric condition which, in the opinion of the treating physician or principal investigator, would unacceptably reduce the safety of the proposed treatment, would impair the delivery of treatment, or would preclude obtaining voluntary informed consent

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel

Basel, 4031, Switzerland

Location

Related Publications (6)

• Spagnoli GC, Zajac P, Marti WR, Oertli D, Padovan E, Noppen C, Kocher T, Adamina M, Heberer M. Cytotoxic T-cell induction in metastatic melanoma patients undergoing recombinant vaccinia virus-based immuno-gene therapy. Recent Results Cancer Res. 2002;160:195-201. doi: 10.1007/978-3-642-59410-6_23.

  PMID: 12079214 BACKGROUND

• Zajac P, Schutz A, Oertli D, Noppen C, Schaefer C, Heberer M, Spagnoli GC, Marti WR. Enhanced generation of cytotoxic T lymphocytes using recombinant vaccinia virus expressing human tumor-associated antigens and B7 costimulatory molecules. Cancer Res. 1998 Oct 15;58(20):4567-71.

  PMID: 9788602 BACKGROUND

• Adamina M, Oertli D. Antigen specific active immunotherapy: lessons from the first decade. Swiss Med Wkly. 2005 Apr 16;135(15-16):212-21. doi: 10.4414/smw.2005.10127.

  PMID: 15971113 BACKGROUND

• Zajac P, Oertli D, Marti W, Adamina M, Bolli M, Guller U, Noppen C, Padovan E, Schultz-Thater E, Heberer M, Spagnoli G. Phase I/II clinical trial of a nonreplicative vaccinia virus expressing multiple HLA-A0201-restricted tumor-associated epitopes and costimulatory molecules in metastatic melanoma patients. Hum Gene Ther. 2003 Nov 1;14(16):1497-510. doi: 10.1089/104303403322495016.

  PMID: 14577912 RESULT

• Oertli D, Marti WR, Zajac P, Noppen C, Kocher T, Padovan E, Adamina M, Schumacher R, Harder F, Heberer M, Spagnoli GC. Rapid induction of specific cytotoxic T lymphocytes against melanoma-associated antigens by a recombinant vaccinia virus vector expressing multiple immunodominant epitopes and costimulatory molecules in vivo. Hum Gene Ther. 2002 Mar 1;13(4):569-75. doi: 10.1089/10430340252809856.

  PMID: 11874634 RESULT

• Adamina M, Rosenthal R, Weber WP, Frey DM, Viehl CT, Bolli M, Huegli RW, Jacob AL, Heberer M, Oertli D, Marti W, Spagnoli GC, Zajac P. Intranodal immunization with a vaccinia virus encoding multiple antigenic epitopes and costimulatory molecules in metastatic melanoma. Mol Ther. 2010 Mar;18(3):651-9. doi: 10.1038/mt.2009.275. Epub 2009 Nov 24.

  PMID: 19935776 RESULT

MeSH Terms

Conditions

Melanoma; Neoplasms; Vaccinia

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Michel Adamina, M.D.

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

• Daniel Oertli, M.D.

  University Hospital, Basel, Switzerland

  STUDY CHAIR

• Michael Heberer, M.D.

  University Hospital, Basel, Switzerland

  STUDY DIRECTOR

• Giulio C Spagnoli, M.D.

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

• Walter R Marti, M.D.

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 29, 2005
• First Posted: June 30, 2005
• Study Start: November 1, 2002
• Primary Completion: July 1, 2007
• Study Completion: December 1, 2008
• Last Updated: December 2, 2009

Record last verified: 2009-12

Locations

CH (1)