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

This is an interventional treatment trial for Melanoma focused on measuring Metastatic Cancer, Immunotherapy, Tumor Regression, Cancer Vaccine, Gene Therapy Read More

• INCLUSION CRITERIA:
• Measurable (per Response Evaluation Criteria in Solid Tumors (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 National Cancer Institute (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 Eastern Cooperative Oncology Group (ECOG) 0 or 1.

• Serology

  • Seronegative for human immunodeficiency virus (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 reverse transcription polymerase chain reaction (RT-PCR) and be hepatitis C virus (HCV) ribonucleic acid (RNA) negative.

• Hematology

  • Absolute neutrophil count (ANC) > 1000/mm(3) without the support of growth factors.
  • White blood cell (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.

• Chemistry

  • Serum Alanine aminotransferase (ALT)/Aspartate aminotransferase (AST) less than or equal to 5.0 times upper limit of normal (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 CRITERIA:

• 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 human chorionic gonadotropin (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.