IDO Peptid Vaccination for Stage III-IV Non Small-cell Lung Cancer Patients. (IDOvaccine)

• ClinicalTrials.gov Identifier: NCT01219348
• Recruitment Status: Completed
• First Posted: October 13, 2010
• Last Update Posted: August 18, 2015
• Sponsor: Inge Marie Svane
• Information provided by (Responsible Party): Inge Marie Svane, Herlev Hospital

Study Description

Brief Summary:

Title: IDO peptid vaccination in combination with immune stimulating agent Aldara and the adjuvant Montanide, for treatment of patients with locally advanced or metastatic non small-cell lung cancer. A first-in-man phase I trial.

Hypothesis: In this trial the investigators assess a new immunotherapeutic strategy targeting the immune inhibiting enzyme, IDO to investigate the potential of vaccination against IDO as a possible anticancer target.

Condition or disease	Intervention/treatment	Phase
NSCLC; Lung Cancer	Biological: IDO peptide vaccination	Phase 1

Detailed Description:

Background: Non small-cell lung cancer (NSCLC) is a common disease with a poor prognosis when locally advanced or metastasized, despite advances in surgery, chemo- and radiation therapy.

In this trial the investigators assess a new immunotherapeutic strategy targeting the immune inhibiting enzyme, IDO to investigate the potential of vaccination against IDO as a possible anticancer target.

IDO has recently been recognized as an important factor in immune regulation and development of immune tolerance in the microenvironment of cancer cells. Cells that represent IDO at their surface are known to inhibit the immune system. IDO expression is seen both in cancer cells and antigen presenting cells. The vaccination against IDO expressing cells is therefore two-sided. The vaccination therapy is thought to block the development of immune tolerance induced by IDO expressing cells. At the same time the investigators aim to stimulate the production of IDO specific T-cells, hence facilitating the elimination of IDO positive tumour cells. The primary end points are safety and toxicity evaluation. Secondary end points are immunological and clinical response.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: IDO Peptid Vaccination in Combination With Immune Stimulating Agent Aldara and the Adjuvant Montanide, for Treatment of Patients With Locally Advanced or Metastatic Non Small-cell Lung Cancer. A First-in-man Phase I Trial.
• Study Start Date: June 2010
• Actual Primary Completion Date: August 2012
• Actual Study Completion Date: August 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Indeolamine 2,3 deoxygenase; To inhibit immune suppression and tolerance, by blocking the IDO enzyme with vaccination against IDO.	Biological: IDO peptide vaccination; Vaccination every second week

Outcome Measures

Primary Outcome Measures :

1. evidence of toxicity [ Time Frame: 12 months ]
   CTCAE = Common Terminology Criteria for Adverse Events v. 3.0 will be used for registration of toxicity

Secondary Outcome Measures :

1. evaluation of immunological and clinical responses [ Time Frame: 18 months ]
   immunological assays will be used to identify immunological responses. CT scans will be used for evaluation of clinical responses.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Histological or cytological verified non small cell lung cancer 2. Metastatic or locally advanced incurable stage III-IV NSCLC 3. Patients need to be off chemotherapy treatment 4. Evaluable disease according to RECIST V. 1,1 criteria 5. Patients must be HLA-A2 positive 6. Patients > 18 years old 7. Performance status 0-1 8. Life expectancy of > 3 months 9. Acceptable bone marrow function, defined as

a. White blood cell count > 2,5 * 109 /l b. Neutrophil count> 1,5 * 109 /l c. Platelet count > 75 * 109/l 10. Creatinin measured < 2,5 * upper limit value 11. Acceptable liver function, defined as

1. ASAT < 100 U/L

2. Bilirubin < 30 U/L 12. Women with child-bearing potential must have controlled s-hcg before inclusion 13. Patients must provide written informed concent before inclusion 13. Termination of chemotherapy treatment > 28 days before inclusion

   14. Termination of radiotherapy treatment > 28 days before inclusion

   15. Inclusion at least > 4 weeks after complicated gastric surgery

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   Exclusion Criteria:

   1. Other malignancies except from non-melanoma skin cancer in the previous 5 years until study inclusion
   2. Brain metastasis are allowed after radical excision, and if the patient at least 1 month afterwards is not in clinical or radiographic progression
   3. Patients with active gastric ulcer disease; patients taking antacid treatment can be included.
   4. Severe medical condition, severe asthma, severe COLD, severe arteriosclerosis or diabetic disease
   5. Acute or chronic infection (ie. HIV, hepatitis, tuberculosis)
   6. Severe allergic reaction or previous anaphylactic shock
   7. Autoimmune diseases (ie. autoimmune neutropenia/thrombopenia, hæmolytic anaemia, systemic lupus erythematosis, Sjøgrens disease, sclerodermia, Goodpastures syndrome, Addisons disease, active Graves disease)
   8. Pregnant or lactating women
   9. Psychiatric disease, which can influence compliance
   10. Known hypersensitivity towards the adjuvance Montanide, the Aldara creme, or adhesive tape.
   11. Treatment with immunosuppressive therapy (ie. dexamethasone, methotrexate)
   12. Treatment with other experimental therapy
   13. Treatment with other anti-cancer therapy, except from treatment of osteoporosis

   14. No systemic chemotherapy, immunotherapy or radiation therapy (except locally) are allowed until 28 days before inclusion.

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Contacts and Locations

Locations

Denmark

Center for Cancer ImmuneTherapy

Herlev, Copenhagen, Denmark, 2730

Center for Cancer Immune Therapy, Dept. og Haematology/Oncology

Copenhagen, Herlev, Copenhagen, Denmark, 2730

Sponsors and Collaborators

Inge Marie Svane

Investigators

• Principal Investigator: Trine Zeeberg Iversen, MD; Center for Cancer Immune Therapy

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Iversen TZ, Engell-Noerregaard L, Ellebaek E, Andersen R, Larsen SK, Bjoern J, Zeyher C, Gouttefangeas C, Thomsen BM, Holm B, Thor Straten P, Mellemgaard A, Andersen MH, Svane IM. Long-lasting disease stabilization in the absence of toxicity in metastatic lung cancer patients vaccinated with an epitope derived from indoleamine 2,3 dioxygenase. Clin Cancer Res. 2014 Jan 1;20(1):221-32. doi: 10.1158/1078-0432.CCR-13-1560. Epub 2013 Nov 11.

Andersen MH. The specific targeting of immune regulation: T-cell responses against Indoleamine 2,3-dioxygenase. Cancer Immunol Immunother. 2012 Aug;61(8):1289-97. doi: 10.1007/s00262-012-1234-4. Epub 2012 Mar 3. Review.

• Responsible Party: Inge Marie Svane, Prof., MD, PhD, Herlev Hospital
• ClinicalTrials.gov Identifier: NCT01219348
• Other Study ID Numbers: LU 1006 - IDO
• First Posted: October 13, 2010
• Last Update Posted: August 18, 2015
• Last Verified: August 2015

Keywords provided by Inge Marie Svane, Herlev Hospital:

IDO enzyme; Vaccination trial; Immunotherapy; NSCLC, stage III_IV; Indeolamine 2,3 dioxygenase = IDO

Additional relevant MeSH terms:

Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases