AzTrials
AzTrials

MelanomaPhase 1/2NCT00116597

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

A Phase 1/2 study testing Intranodal immunization with a recombinant vaccinia virus expressing 5 transgenes and Intranodal booster immunizations with synthetic melanoma associated epitopes in people with Melanoma, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
Intranodal immunization with a recombinant vaccinia virus expressing 5 transgenes and Intranodal booster immunizations with synthetic melanoma associated epitopes
Type of treatment
Vaccines
How many people
15 participants
Where
1 siteSwitzerland
Study dates
Nov 2002to Dec 2008
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%

Who cannot join

  • 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
Show all 17Show fewer
  • 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
  • Patients receiving any other concurrent investigational treatment, or any other concurrent treatment for their cancer
  • Patients who cannot avoid close contact with children less than 3 years of age or with immunocompromised household members

Trial locations and contacts

1 site in 1 country.

Switzerland1 site

  • University Hospital Basel

    Basel, 4031

Other trials in Switzerland

About this study

Official title: Active Specific Intranodal Immunotherapy With a Recombinant Vaccinia Virus Expressing Three Melanoma Associated Epitopes and Two Costimulatory Molecules, Followed by Immunization With Synthetic Melanoma Associated Epitopes. A Phase I/II Trial in Patients With Stages IIb to IV Melanoma

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.

Read the detailed description

The investigators have conducted a phase I/II clinical trial based on the intradermal administration to stage III/IV melanoma patients of a recombinant vaccinia virus encoding tumor associated antigens and costimulatory epitopes for the priming of immune responses, followed by boosts with corresponding synthetic peptides (Zajac P et al in Human Gene Ther 2003). Specific cytotoxic T cells could be induced in a majority of patients following priming, but sustained responsiveness could not be maintained by peptide boosting on a long term basis. Emerging evidence supports the notion that expansion of specific T cells requires trafficking of antigen presenting cells loaded with specific determinants to lymphatic nodes, as induced, among others, by pro-inflammatory stimuli. Therefore, we now adopt the intranodal injection of the immunogenic formulations. As for the former melanoma active specific immunotherapy trial, GM-CSF is used as a supporting cytokine. The epitopes considered are expressed, either all or some of them, in over 90% of the melanomas in Western countries; namely, we immunize with Mart-1/Melan-A epitope 27-35, Gp-100 epitope 280-288 and tyrosinase epitope 1-9. As a consequence, HLA-A2 positivity is mandatory for inclusion in the trial. The 2 costimulatory molecules expressed by cells infected with our replication-incompetent recombinant vaccinia virus are B7.1 (CD80) and B7.2 (CD86).

Conditions
Melanoma
Being tested
Intranodal immunization with a recombinant vaccinia virus expressing 5 transgenes, Intranodal booster immunizations with synthetic melanoma associated epitopes
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
Medical subject headings
Melanoma, Neoplasms, Vaccinia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Intranodal immunization with a recombinant vaccinia virus expressing 5 transgenesGenetic

  • Intranodal booster immunizations with synthetic melanoma associated epitopesBiological

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety evaluation

  2. Clinical response

  3. Immune response assessment

Secondary outcomes (2)

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

  2. Dose adaptation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jun 2005 (estimated)
  2. Study startNov 2002
  3. Primary completionJul 2007
  4. Study completionDec 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00116597
Sponsor's protocol ID
GT1999017/05.050
Other IDs
SNF grant NPF 37 4037-55151
Status last verified
Dec 2009
First submitted
29 Jun 2005
Last updated
2 Dec 2009
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 12079214

  • 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.

    PubMed 9788602

  • 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.

    PubMed 15971113

  • 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.

    PubMed 14577912

  • 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.

    PubMed 11874634

  • 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.

    PubMed 19935776

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Intranodal immunization with a recombinant vaccinia virus expressing 5 transgenes and Intranodal booster immunizations with synthetic melanoma associated epitopes in people with Melanoma, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Dec 2009. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety evaluation. The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00116597, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2009.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in