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

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.

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.

Study Overview

• Status: Completed
• Conditions: NSCLC; Lung Cancer
• Intervention / Treatment: Biological: IDO peptide vaccination

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 Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen
    • Herlev, Copenhagen, Denmark, 2730
      • Center for Cancer ImmuneTherapy
  • Herlev, Copenhagen
    • Copenhagen, Herlev, Copenhagen, Denmark, 2730
      • Center for Cancer Immune Therapy, Dept. og Haematology/Oncology

Participation Criteria

Eligibility Criteria

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

Description

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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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evidence of toxicity	CTCAE = Common Terminology Criteria for Adverse Events v. 3.0 will be used for registration of toxicity	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evaluation of immunological and clinical responses	immunological assays will be used to identify immunological responses. CT scans will be used for evaluation of clinical responses.	18 months

Collaborators and Investigators

• Sponsor: Inge Marie Svane
• Investigators: Principal Investigator: Trine Zeeberg Iversen, MD, Center for Cancer Immune Therapy

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: May 10, 2010
• First Submitted That Met QC Criteria: October 12, 2010
• First Posted (Estimate): October 13, 2010

Study Record Updates

• Last Update Posted (Estimate): August 18, 2015
• Last Update Submitted That Met QC Criteria: August 17, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Immunotherapy; IDO enzyme; Vaccination trial; NSCLC, stage III_IV; Indeolamine 2,3 dioxygenase = IDO
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: LU 1006 - IDO