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Messenger RNA (mRNA)-Based, Personalized Cancer Vaccine Against Neoantigens Expressed by the Autologous Cancer

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ClinicalTrials.gov Identifier: NCT03480152
Recruitment Status : Recruiting
First Posted : March 29, 2018
Last Update Posted : November 2, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

Exome sequencing can identify certain gene mutations in a person s tumor. This can then be used to create cancer treatments. In this study, researchers will make a treatment called an mRNA vaccine. The vaccine might cause certain tumors to shrink.

Objective:

To see if the mRNA vaccine is safe and can cause metastatic melanoma or epithelial tumors to shrink.

Eligibility:

People 18-70 years old with metastatic melanoma or epithelial cancer

Design:

Participants will be screened under protocol 99-C-0128.

Participants will provide samples under protocol 03-C-0277:

Participants will provide a piece of their tumor from a previous surgery or biopsy.

Participants will have leukapheresis: Blood is removed through a needle in one arm and circulated through a machine that takes out the white blood cells. The blood is then returned through a needle in the other arm.

Participants will have many tests:

Scans and x-rays

Heart and lung function tests

Blood and urine tests

Participants will receive the mRNA vaccine every 2 weeks for up to 8 weeks. They will get the vaccine as an injection into the upper arm or thigh. They may receive a second course of vaccines if the study doctor determines it is needed.

Participants will have follow-up visits approximately 2 weeks after their final vaccine, then 1 month later, then every 1-2 months for the first year, and then once a year for up to 5 years. Each visit may take up to 2 days and include:

Physical exam

Blood tests

Scans

Leukapheresis at the first visit


Condition or disease Intervention/treatment Phase
Melanoma Colon Cancer Gastrointestinal Cancer Genitourinary Cancer Hepatocellular Cancer Biological: NCI-4650, a mRNA-based, Personalized Cancer Vaccine Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Trial to Evaluate the Safety and Immunogenicity of a Messenger RNA (mRNA)-Based, Personalized Cancer Vaccine Against Neoantigens Expressed by the Autologous Cancer
Actual Study Start Date : May 18, 2018
Estimated Primary Completion Date : May 31, 2026
Estimated Study Completion Date : May 31, 2028

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 1/Phase I Arm
Escalating doses of mRNA vaccine
Biological: NCI-4650, a mRNA-based, Personalized Cancer Vaccine
Patients may receive a mRNA-based vaccine intramuscularly at two-week intervals for four cycles. Patients may be vaccinated with a second and final course of treatment using the same vaccine dose. The second course may start approximately four weeks (plus or minus 2 weeks) from the last vaccine dose.

Experimental: 2/Phase II Arm
MTD of mRNA vaccine established in Phase I
Biological: NCI-4650, a mRNA-based, Personalized Cancer Vaccine
Patients may receive a mRNA-based vaccine intramuscularly at two-week intervals for four cycles. Patients may be vaccinated with a second and final course of treatment using the same vaccine dose. The second course may start approximately four weeks (plus or minus 2 weeks) from the last vaccine dose.




Primary Outcome Measures :
  1. Response rate [ Time Frame: 2 weeks after last vaccine, then 1 month later x1, then every 1-2 months for the 1st year, and then annually for up to 5 years or until clinically proven progressive disease ]
    Percentage of patients who have a clinical response to treatment (objective tumor regression)

  2. Frequency of treatment-related adverse events [ Time Frame: 30 days after the first follow-up evaluation (at the second follow-up evaluation) ]
    Aggregate of treatment related adverse events, as well as their frequency and severity


Secondary Outcome Measures :
  1. Measure persistence [ Time Frame: Approximately 2 weeks after last vaccine ]
    Quantity and quality of circulating antigen-specific T cells



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.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Measurable (per RECIST v1.1 criteria), metastatic melanoma, gastrointestinal, or genitourinary cancer with at least one lesion that is resectable. Only patients with metastatic gastrointestinal cancer will be eligible for enrollment on the Phase I portion of the study. Patients with metastatic melanoma, gastrointestinal, or genitourinary cancer will be eligible for enrollment on the Phase II portion of the study.
  • Confirmation of diagnosis of metastatic cancer by the NCI Laboratory of Pathology.
  • Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible.
  • Prior therapy with at least one first-line standard of care treatment or second-line treatment of proven effectiveness. Patients must have progressive disease after prior treatment. Prior first-or second-line treatments would include the following:

    • Patients with metastatic melanoma: Receipt of a checkpoint inhibitor as first-line therapy
    • Patients with metastatic melanoma with an activating mutation of KIT: Receipt of Imatinib
    • Patients with a BRAF V600 activating mutation: Receipt of appropriate targeted therapy
    • Patients with metastatic gastrointestinal cancer: Receipt of up to two forms of approved first- and/or second-line chemotherapy regimens
    • Patients with metastatic genitourinary cancers: Receipt of a first- or second-line therapy appropriate for their histologic subtype
  • Age greater than or equal to 18 years and less than or equal to 70 years.
  • Clinical performance status of ECOG 0 or 1.
  • Serology

    • Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive may have decreased immune-competence and thus may be less responsive to the experimental treatment and more susceptible to its toxicities.)
    • Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then the patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
  • Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.
  • Hematology

    • ANC > 1000/mm(3) without the support of growth factors.
    • WBC greater than or equal to 3000/mm(3)
    • Platelet count greater than or equal to 100.000/mm(3)
    • Hemoglobin > 8.0 g/dl. Subjects may be transfused to reach this cut-off.
    • CD4 count > 200/microl. Only for subjects whose targeted antigens are only recognized by CD4+ cells.
  • Chemistry

    • Serum ALT/AST < 5.0 times ULN
    • Serum creatinine <1.5 times ULN or measured creatinine clearance (calculated using Cockcroft-Gault formula) > 40 ml/min
    • Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert s Syndrome, who must have a total bilirubin < 3.0 mg/dl.
  • More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the immunization regimen, and patients toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
  • Ability of subject to understand and the willingness to sign a written informed consent document.
  • Subjects must be co-enrolled on protocol 03-C-0277.

EXCLUSION CRIETERIA:

  • Pregnant or breastfeeding women who do not consent to stop breast-feeding while on study treatment and for 30 days after the use of the investigational vaccine where pregnancy is confirmed by a positive, rising hCG laboratory test.

    • Women of child-bearing potential, defined as all women capable of becoming pregnant, unless they agree to use an appropriate method of contraception during dosing and for 120 days after the last dose (i.e., final vaccine). Effective contraception methods include a combination of any two of the following (unless method is abstinence or sterilization, in which only one method is required):

      • Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%). In case of use of oral contraception, women should have been stable on the same pill for a minimum of 6 months before taking study treatment.
      • Placement of an intrauterine device or intrauterine system.
      • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
      • Total abstinence
      • Female sterilization at least eight weeks before taking study treatment.
      • Male sterilization (at least six months prior to screening).
  • Sexually active males must use a condom during intercourse during dosing and for 120 days after the last dose (i.e., final vaccine), and should not father a child in this period.
  • Any systemic steroid therapy or other form of immunosuppressive therapy within 7 days of the first dose of the vaccine. A physiologic dose of systemic corticosteroids may be approved. Inhaled or topical steroids, and less than or equal to 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
  • Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses of the cardiovascular, respiratory, or immune system.
  • Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  • Concurrent opportunistic infections (the experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
  • Any vaccinations four weeks prior to the first vaccination cycle or live vaccines at any time during the study.

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): NCT03480152


Contacts
Contact: Ellen Bodurian (866) 820-4505 IRC@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center    866-820-4505    irc@nih.gov   
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Steven A Rosenberg, M.D. National Cancer Institute (NCI)

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03480152     History of Changes
Other Study ID Numbers: 180074
18-C-0074
First Posted: March 29, 2018    Key Record Dates
Last Update Posted: November 2, 2018
Last Verified: October 26, 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Metastatic Cancer
Immunotherapy
Tumor Regression
Cancer Vaccine
Gene Therapy

Additional relevant MeSH terms:
Gastrointestinal Neoplasms
Liver Neoplasms
Carcinoma, Hepatocellular
Urogenital Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Liver Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Vaccines
Immunologic Factors
Physiological Effects of Drugs