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Arginase-1 Peptide Vaccine in Patients With Metastatic Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03689192
Recruitment Status : Recruiting
First Posted : September 28, 2018
Last Update Posted : February 12, 2020
Sponsor:
Information provided by (Responsible Party):
Inge Marie Svane, Herlev Hospital

Brief Summary:
In this phase I first-in-humans-study a vaccine consisting of arginase-1 (ARG1) peptides and the adjuvant Montanide ISA-51 will be tested in ten patients with metastatic solid tumors. Patients will be treated with an ARG1 vaccine every third week for 45 weeks.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Urothelial Carcinoma Malignant Melanoma Ovarian Cancer Colorectal Cancer Breast Cancer Squamous Cell Carcinoma of the Head and Neck Metastatic Cancer Biological: ARG1-18,19,20 Phase 1

Detailed Description:

Arginase-1 (ARG1) is an enzyme that converts the amino acid arginine into urea and ornithine. ARG1 is mainly expressed in hepatocytes but different myeloid cells are also capable of ARG1-expression.

An ARG1-induced arginine depletion suppresses T cell function through the impairment of the T cell receptor (TCR)-complex. A research group from the Center for Cancer Immune Therapy (CCIT) have identified spontaneous T cell reactivity against ARG1 peptides in peripheral blood mononuclear cells of cancer patients and healthy donors. The theoretic background for an ARG1 peptide vaccine is to activate ARG1-specific T cells to infiltrate the tumor microenvironment and eliminate ARG1-expressing immunosuppressive cells. The aim is to treat 10 patients with progressive solid tumors following treatment with standard of care agents. Patients will receive ARG1 vaccinations administered subcutaneously every third week for 45 weeks.

The primary endpoint is to evaluate safety and toxicity. Immune responses will be assessed using blood- and tumor tissue samples and clinical responses are evaluated using RECIST 1.1.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Arginase-1 Peptide Vaccine in Patients With Metastatic Solid Tumors
Actual Study Start Date : December 17, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : June 2021


Arm Intervention/treatment
Experimental: ARG1-18,19,20 peptide vaccine
One ARG1-vaccine every third week for 45 weeks.
Biological: ARG1-18,19,20
300 ug ARG1-18,19,20 peptide in water mixed with 500ul montanide




Primary Outcome Measures :
  1. Adverse events evaluated by CTCAE 4.0 [ Time Frame: One year ]
    Adverse events are graded 1-5 according to the criteria


Secondary Outcome Measures :
  1. Immune responses [ Time Frame: One year ]
    To evaluate the immunological impact of the ARG1-18,19,20 peptide vaccines using blood samples and tumor biopsies.

  2. Overall Survival [ Time Frame: One year ]
    Overall Survival (OS) defined as time from treatment initiation to death, will be described with use of Kaplan Meier curve.

  3. 4.Progression free survival [ Time Frame: One year ]
    Progression free survival (PFS) defined as the time from treatment initiation to disease progression, relapse or death due to any cause, which ever comes first, will be described with Kaplan Meier curve.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  1. Age ≥ 18
  2. The patient has metastatic solid tumors (NSCLC, colorectal cancer, urothelial cancer, breast cancer, ovarian cancer, malignant melanoma or HNSCC); progressive or recurrent disease on or following treatment with standard of care agents
  3. At least one measurable parameter according to RECIST 1.1.
  4. The patient has an ECOG performance status of 0 or 1
  5. Life expectancy of at least 3 months
  6. Prior PD1/PD-L1 allowed
  7. The patient is a female of childbearing potential with negative pregnancy test
  8. For fertile women: Agreement to use contraceptive methods with a failure rate of < 1 % per year during the treatment period and for at least 150 days 12 weeks after the treatment. Safe contraceptive methods for women are birth control pills, intrauterine device, contraceptive injection, contraceptive implant, contraceptive patch or contraceptive vaginal ring.
  9. For men: Agreement to use contraceptive measures and agreement to refrain from donating sperm
  10. The patient has met the following hematological and biochemical criteria:

    1. AST and ALT ≤2,5 X ULN or ≤5 X ULN with liver metastases
    2. Serum total bilirubin ≤1,5 X ULN or direct bilirubin ≤ ULN for patient with total bilirubin level > 1,5 ULN
    3. Serum creatinine ≤1,5 X ULN
    4. ANC (Absolute Neutrophil Count) ≥1,000/mcL
    5. Platelets ≥ 75,000 /mcL
    6. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
  11. Mandatory provision of archival tissue and blood for biomarker testing at baseline
  12. Mandatory provision of blood for biomarker testing during the study
  13. Signed declaration of consent after oral and written information about the protocol

Exclusion Criteria:

  1. The patient has not recovered from surgery or is less than 4 weeks from major surgery
  2. The patient has a history of life-threatening or severe immune related adverse events on treatment with another immunotherapy and is considered to be at risk of not recovering
  3. The patient is expected to require any other form of systemic antineoplastic therapy or radiation therapy while receiving the treatment. However, radiation therapy treatment of non target lesion is allowed.
  4. The patient has a history of severe clinical autoimmune disease
  5. The patient has a history of pneumonitis, organ transplant, human immunodeficiency virus positive, active hepatitis B or hepatitis C
  6. The patient requires systemic steroids for management of immune-related adverse events experienced on another immunotherapy
  7. The patient has any condition that will interfere with patient compliance or safety (including but not limited to psychiatric or substance abuse disorders)
  8. The patient is pregnant or breastfeeding
  9. The patient is unable to voluntarily agree to participate by signed informed consent or assent
  10. The patient has an active infection requiring systemic therapy
  11. The patient has received a live virus vaccine within 30 days of planned start of therapy
  12. Significant medical disorder according to investigator; e.g. severe asthma or chronic obstructive lung disease, dysregulated heart disease or dysregulated diabetes mellitus
  13. Concurrent treatment with other experimental drugs
  14. Concurrent treatment with Valproate or Xanthin Oxidase inhibitors
  15. Known side effects to Montanide ISA-51
  16. Any active autoimmune diseases e.g. autoimmune neutropenia, thrombocytopenia or hemolytic anemia, systemic lupus erythematosus, scleroderma, myasthenia gravis, autoimmune glomerulonephritis, autoimmune adrenal deficiency, autoimmune thyroiditis etc.
  17. Severe allergy or anaphylactic reactions earlier in life

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03689192


Contacts
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Contact: Cathrine L. Lorentzen, MD +45 38683868 cathrine.lund.lorentzen@regionh.dk
Contact: Inge Marie Svane, Prof., MD +45 38683868 inge.marie.svane@regionh.dk

Locations
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Denmark
Center for Cancer Immune Therapy Dept. of Hematology/oncology Recruiting
Copenhagen, Herlev, Denmark, 2730
Contact: Inge Marie Svane, Prof., MD    +4538683868    inge.marie.svane@regionh.dk   
Contact: Cathrine Lorentzen, MD    +4538683868    cathrine.lund.lorentzen@regionh.dk   
Sponsors and Collaborators
Herlev Hospital

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Responsible Party: Inge Marie Svane, MD, Professor, Herlev Hospital
ClinicalTrials.gov Identifier: NCT03689192    
Other Study ID Numbers: AA1809
First Posted: September 28, 2018    Key Record Dates
Last Update Posted: February 12, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Inge Marie Svane, Herlev Hospital:
Arginase 1
Additional relevant MeSH terms:
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Carcinoma
Melanoma
Carcinoma, Transitional Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Vaccines
Immunologic Factors
Physiological Effects of Drugs