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A Personalized NeoAntigen Cancer Vaccine Combined With Anti-PD-1 in Melanoma

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: NCT04072900
Recruitment Status : Not yet recruiting
First Posted : August 28, 2019
Last Update Posted : August 28, 2019
Sponsor:
Information provided by (Responsible Party):
pfkchenxiang, Xiangya Hospital of Central South University

Brief Summary:
This study assessed the safety and efficacy of individualized new antigen cancer vaccine combined with Programmed Cell Death Protein 1(PD1) inhibitor Toripalimab in the treatment of metastatic cutaneous melanoma. Melanoma is the most malignant skin neoplasm. Immunotherapy is the main treatment at present. PD1 is an immunological checkpoint and the inhibitors can reduce the immune escape of tumors, enhance T cell function and kill tumors. At present, PD1 antibody is the representative drug of immunotherapy, but the overall efficiency of its single drug treatment of acral melanoma is still low, and the combined treatment can significantly improve the efficiency. Melanoma has a high mutation load, which makes each patient have mutations specific to individual patients and tumors (changes in genetic material). These mutations lead to tumour cells producing proteins that are distinct from those of the body's own cells. These proteins used in vaccines may cause a strong immune response, which may help participants' bodies fight against any cancer cells that may lead to future recurrence of melanoma. Inhibition of PD1 can enhance the activity of T cells and form T cells with sustained killing activity. Tumor vaccines activate human Antigen Presenting Cells (APC) by injecting tumor antigens and adjuvants, and then activate T cells by APC to produce specific killing T cells. Therefore, the combination of "tumor vaccine + PD1 inhibitor" can produce effective specific killing and sustained activation of T cells, and prevent the establishment of inhibitory tumor microenvironment by tumor cells. The study will examine the safety and efficiency of the combined therapy at different time points and assess whether there is an immune response in the patient's peripheral blood and tumor tissue.

Condition or disease Intervention/treatment Phase
Melanoma (Skin) Drug: Peptide Drug: Anti-PD-1 Drug: rhGM-CSF Drug: Imiquimod 5% Topical Cream Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study With a Personalized NeoAntigen Cancer Vaccine Combined With Anti-PD-1 in Metastatic Melanoma
Estimated Study Start Date : September 1, 2019
Estimated Primary Completion Date : September 1, 2021
Estimated Study Completion Date : September 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Intervention/Treatment

Personalized NeoAntigen Cancer Vaccine- Neo-Vac-Mn (peptides + rhGM-CSF+anti-PD1+Imiquimod 5% Topical Cream)

NeoAntigen peptides:4 x 2 mg the total peptides given on days 84,87,91,98,105,133,and 161

Anti-PD-1 Toripalimab: 3mg/kg, ivgtt, Q2w

rhGM-CSF: 3μg/kg given on Days 81,82,83,95,96,97,102,103,104,130,131,132,158,159,and 160

Imiquimod 5% Topical Cream:topical application on the injection site 6 hours before each NeoAntigen peptides injection

Drug: Peptide
4 x 3 mg all the peptides given on days 84,87,91,98,105,133,and 161
Other Name: NeoAntigen peptides

Drug: Anti-PD-1
3mg/kg, ivgtt, Q2w
Other Name: Toripalimab

Drug: rhGM-CSF
3μg/kg given on Days 81,82,83,95,96,97,102,103,104,130,131,132,158,159,and 160

Drug: Imiquimod 5% Topical Cream
topical application on the injection site 6 hours before each NeoAntigen peptides injection




Primary Outcome Measures :
  1. Number of participants experiencing adverse events [ Time Frame: up to a maximum of 252 days ]
    Number of participants experiencing clinical and laboratory adverse events (AE)

  2. Number of Patients with Complete Remission Rate [ Time Frame: up to a maximum of 252 days ]
    Number of Patients with Complete Remission Rate(CRR)

  3. Number of Patients with Progressive Disease [ Time Frame: up to a maximum of 252 days ]
    Number of Patients with Progressive Disease(PD)

  4. Number of Patients with Partial Response [ Time Frame: up to a maximum of 252 days ]
    Number of Patients with Partial Response(PR)


Secondary Outcome Measures :
  1. Monitoring of cellular immune response [ Time Frame: up to a maximum of 252 days ]
    the immune response of serum and tumor tissue



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 to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must meet the following criteria on screening examination to be eligible to participate in the study:
  2. Patient is willing and able to give written informed consent.
  3. Age ≥ 18 years, ≤75 years
  4. Pathologically confirmed, clinically evident (by physical examination or radiographic imaging) stage IIIDN3c、IVM1a、M1b、M1c cutaneous melanoma.
  5. Lesions that can be measured,and at least one lesion that can be used to evaluate the efficacy of immunotherapy;Multiple biopsies are available for lesions.
  6. Patient is agreeable to allow tumor、normal tissue samples and blood samples to be submitted for genomic/complete exome/transcriptional sequencing;
  7. ECOG score is 0 or 1
  8. Life expectancy >6 months
  9. Normal organ and bone marrow function as defined below:

    Leukocytes ≥ 3,500/mcL Absolute lymphocyte count > 800/mcL Absolute neutrophil count > 1,500/mcL Platelets > 100,000/mcL Hemoglobin > 10.0 g/dL Total serum bilirubin < 1.0 x institutional upper limit of normal AST (SGOT)/ALT (SGPT) < 2.0 x institutional upper limit of normal Serum creatinine< 1.5 x institutional upper limit of normal

  10. Women of childbearing potential (WOCBP) must have a negative pregnancy test before entering the trial and within 7 days prior to start of study medication.
  11. Female patients enrolled in the study, short-term have no fertility plan and must agree to use an adequate method of contraception starting with the first dose of study therapy through 90 days after the last dose of study therapy.
  12. Male patients must agree to use an adequate method of contraception starting with the first dose of study therapy through 90 days after the last dose of study therapy.
  13. Good compliance, able to follow research protocols and follow-up procedures.

Exclusion Criteria:

  1. Patients who meet any of the following criteria will not be eligible for this study.
  2. Uveal or mucosal melanoma;
  3. Patients who received immunotherapy or other targeted cancer therapy within 4 weeks (including, but not limited to: IL-2, CTLA-4 blockade, PD-1/PD-L1 blockade, but exception of INF-α given as adjuvant treatment)
  4. Previous bone marrow or stem cell transplant
  5. History of severe allergic reactions attributed to any vaccine therapy
  6. Active, known, or suspected autoimmune disease with the exception of vitiligo, type 1 diabetes, or psoriasis not requiring systemic treatment.
  7. Use of a non-oncology vaccine therapy for prevention of infectious diseases (up-to) 4 weeks prior to enrollment to the study. Patients may not receive any non-oncology vaccine therapy during the period of NeoVax administration and until at least 8 weeks after the last dose of study therapy
  8. In an immunosuppressive stage or immunosuppressive drugs were used systematically within 2 weeks.
  9. Patients with long-term use of glucocorticoids or with experimental anti-tumor drugs
  10. Active bacterial or fungal infections identified clinically (>= level 2 of NCI-CTC edition 3);
  11. Known chronic infections with HIV, hepatitis B or C
  12. Known active or latent tuberculosis infection
  13. A history of idiopathic pulmonary fibrosis and organized pneumonia, or active pneumonia on chest computed tomography.
  14. Complicated with other tumors, except for cervical cancer in situ and basal cell carcinoma five years ago.
  15. Severe coronary or cerebrovascular disease, or other diseases that the investigators considered should to be exclusion;
  16. Drug abuse, Clinical, psychological or social factor result in affecting informed consent or research implementation.

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): NCT04072900


Contacts
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Contact: Xiang Chen, Doctor's +86-8975-3406 chenxiangck@126.com
Contact: Juan Su, Doctor's _86-8432-8478 sujuanderm@csu.edu.cn

Locations
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China, Hunan
Xiangya Hospital, Central South University
Changsha, Hunan, China, 410008
Contact: Juan Su    +86-8432-7128    sujuanderm@csu.edu.cn   
Contact: Xiang Chen    +86-8975-3406    chenxiangck@126.com   
Sponsors and Collaborators
Xiangya Hospital of Central South University
Investigators
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Principal Investigator: Xiang Chen, Doctor's Xiangya Hospital of Central South University

Publications of Results:
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Responsible Party: pfkchenxiang, Chen Xiang, Principal Investigator,Clinical Professor,Vice-President, Xiangya Hospital of Central South University
ClinicalTrials.gov Identifier: NCT04072900    
Other Study ID Numbers: XYM001
First Posted: August 28, 2019    Key Record Dates
Last Update Posted: August 28, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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 pfkchenxiang, Xiangya Hospital of Central South University:
Melanoma, Metastasis
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Imiquimod
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Antineoplastic Agents
Interferon Inducers