Ability of a Dendritic Cell Vaccine to Immunize Melanoma or Epithelial Cancer Patients Against Defined Mutated Neoantigens Expressed by the Autologous Cancer
Condition: Melanoma; Gastrointestinal Cancer; Breast Cancer; Ovarian Cancer; Pancreatic Cancer
MeSH terms: Melanoma; Gastrointestinal Neoplasms
Intervention: Peptide loaded dendritic cell vaccine
Intervention description: On days 0, 14 (+/- 5 days), 28 (+/- 5 days), and 42 (+/- 5 days). The vaccine will be administered as both an intravenous (IV) infusion and a subcutaneous (SQ) injection. The total dose will be divided equally between intravenous (IV) and SQ containing 1.0E7 to 8.0E7 cells per cycle depending upon the manufacturing yield.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Cell Therapy; Immunotherapy; Vaccines

Summary:

      Background:

      Exomes are the parts of deoxyribonucleic acid (DNA) that make proteins. Researchers are
      finding a way to read the letters in the exome. Incorrect letters are called mutations.
      Tumors contain specific mutations. Researchers can find these mutations in tumors to make
      treatments. Researchers want to use pieces of participants tumors to find the tumor-specific
      mutations. They also will take participants white blood cells to make a vaccine that they
      hope will shrink the tumors.

      Objectives:

      To see if dendritic vaccine tumor-fighting cells are safe and can cause certain cancer tumors
      to shrink.

      Eligibility:

      Adults ages 18-70 who have metastatic melanoma or metastatic epithelial cancer

      Design:

      The first part of this study was done under protocol 03-C-0277. In that study, white blood
      cells and pieces of participants' tumors were taken to make a vaccine.

      In this study, participants will get a vaccine every 2 weeks for 8 weeks. It will be given
      both in a vein and under the skin. At each visit, participants will have a physical exam and
      have blood taken. They will talk about any side effects they have.

      After treatment ends, participants will have many follow-up visits for the first year, then
      once each year after that. Visits will last up to 2 days each. They will include lab tests,
      imaging studies, and a physical exam. Blood will be taken at each visit. At the first
      follow-up visit, participants may have leukapheresis, which they also had as part of protocol
      03-C-0277. Participants may not have to return to the Clinical Center for these visits.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Metastatic melanoma or epithelial cancer with at least one lesion that is resectable
             or in selected cases, available peripheral blood mononuclear cells (PBMCs)

          -  Measurable and evaluable metastatic disease per Response Evaluation Criteria in Solid
             Tumors (RECIST) 1.1 criteria

          -  Confirmation of the diagnosis of metastatic cancer by the Laboratory of Pathology of
             National Cancer Institute (NCI).

          -  All patients must be refractory to approved standard systemic therapy.

          -  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.

          -  Greater than or equal to 18 years of age and less than or equal to 70 years of age.

          -  Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0, 1, 2

          -  Patients of both genders must be willing to practice birth control from the time of
             enrollment on this study and for up to four months after treatment.

          -  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 can have decreased immune-competence and thus
                  are 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 transcriptase polymerase chain reaction (RT-PCR)
                  and be hepatitis C virus ribonucleic acid (HCV RNA) negative.

          -  Hematology

               -  Absolute neutrophil count greater than 1000/mm^3 without the support of
                  filgrastim

               -  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.

               -  Cluster of differentiation 4 (CD4) count > 200/uL

          -  Chemistry:

               -  Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than
                  5.0 x ULN

               -  Serum Creatinine less than or equal to 1.6 mg/dl

               -  Total bilirubin less than or equal to 2.0 mg/dl, except in patients with
                  Gilbert's Syndrome, who must have a total bilirubin less than or equal to 3.0
                  mg/dl.

          -  More than four weeks must have elapsed since any prior systemic therapy at the time
             the patient receives the vaccine, and patients toxicities must have recovered to a
             grade 1 or less (except for toxicities such as alopecia or vitiligo).

        Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as
        long as all toxicities have recovered to grade 1 or less.

          -  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:

          -  Women of child-bearing potential who are pregnant or breastfeeding because of the
             potentially dangerous effects of the treatment on the fetus or infant.

          -  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).

          -  Active systemic infections (requiring anti-infective treatment), coagulation disorders
             or any other active or uncompensated major medical illnesses.

          -  Patients who are receiving any other investigational agents.