PANVAC-V and PANVAC-F Vaccines Plus Sargramostim to Treat Advanced Cancer
Condition: Adenocarcinoma; Colorectal Cancer; Ovarian Cancer; Breast Cancer
MeSH terms: Adenocarcinoma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Background:

        -  Many cancers produce two proteins, carcinoembryonic antigen (CEA) and mucin-1 (MUC-1).

        -  The PANVAC-V (PANVAC vaccinia) priming vaccine and PANVAC-F (PANVAC fowlpox) boosting
           vaccine contain human genes that cause production of CEA and MUC-1, which can be used as
           a target for the immune system to attack the cancer. The vaccines also contain genes
           that cause production of other proteins that enhance immune activity.

        -  Sargramostim is a protein that boosts the immune system.

      Objectives:

        -  To evaluate the safety and effectiveness of PANVAC-V and PANVAC-F in patients with
           advanced cancer.

        -  To document the immune response to the vaccines and any anti-tumor responses that may
           occur.

      Eligibility: Patients 18 years of age and older with advanced cancer whose tumors produce CEA
      or MUC-1 protein

      Design:

        -  This trial has three cohorts: the first cohort includes 10 patients with advanced
           colorectal cancer and 10 to 15 patients with any advanced non-colorectal cancer that
           produces either EA or mitochondrial Ca2+ uniporter 1 (MCU-1); the second cohort includes
           12 patients with advanced breast cancer and the third cohort includes 14 patients with
           advanced ovarian cancer.

        -  All patients receive PANVAC-V on study day 1, followed by PANVAC-F on days 15, 29 and 43
           then every 28 days for up to 12 vaccines followed by every 3 months until disease
           progression or toxicity. The vaccines are given by injection under the skin.
           Sargramostim is injected at the vaccination site on the day of each vaccination and for
           the next 3 days following vaccination.

        -  Patients whose scans show that their disease has progressed, but who are otherwise
           clinically stable may revert back to monthly injections.

        -  Patients undergo apheresis to collect white blood cells (lymphocytes) on day 1 and day
           71 of the study to measure the immune response to the treatment. Blood is collected
           through a needle placed in one arm and directed through a cell separator machine where
           the lymphocytes are extracted. The rest of the blood components are returned to the
           patient through the same needle.

        -  Patients are monitored with frequent blood tests and periodic imaging tests (scans) to
           monitor for safety and the response to treatment.
    

Detailed description: 
      Background:

        -  Carcinoembryonic antigen (CEA) and mucin-1 (MUC-1) are overexpressed in multiple
           adenocarcinomas.

        -  Pox viral vectors can induce a strong immune response to CEA and MUC-1.

        -  The use of agonist epitopes within the tumor associated antigen (TAA) can induce a
           better immune response than native peptides and have been associated with clinical
           responses

        -  Heterologous prime and boost regimens are superior in terms of generalizing immune
           responses; and this may translate into improved clinical responses

        -  The use of granulocyte-macrophage colony-stimulating factor (GM-CSF) does not add
           significant toxicity and in pre-clinical models is essential for induction for optimal
           immune responses.

        -  It is possible by using vectors directed against TAA that there may be additive or
           synergistic immune responses and this may be important in overcoming antigenic escape
           variance

        -  Evidence of clinical benefit has been noted in some patients treated with this vaccine

      Objectives:

        -  For colorectal cancer and non-colorectal cancer Cohort: To evaluate the safety and
           tolerability of the vaccine.

        -  For the Ovarian Cancer and Breast Cancer Cohorts: To evaluate clinical response to the
           vaccine.

      Eligibility:

        -  In the first cohort (colorectal and non-colorectal cancer), histologically confirmed
           adenocarcinoma that is CEA or MUC-1 positive described as metastatic disease (measurable
           or evaluable) or metastatic disease documented by biopsy but not evaluable by imaging
           (e.g. small volume peritoneal disease)

        -  For the ovarian and breast cancer cohorts, patients must have evaluable disease

        -  Normal organ function, Eastern Cooperative Oncology Group (ECOG) 0-1

      Design:

        -  This is a non-randomized three cohort, pilot trial of pox viral vaccines that contain
           the transgenes for CEA and MUC-1 (both with modified human leukocyte antigen A2 (HLA-A2)
           agonist epitopes) as well as 3 human T-cell costimulatory molecules, B7-1, ICAM-1
           (CD54), and LFA-3 (CD58) [PANVAC(TM)-V (vaccinia) and PANVAC(TM)-F (fowlpox)] in
           patients with metastatic carcinoma that express CEA or MUC-1 antigen.

        -  The first cohort will enroll 10 patients with metastatic colorectal adenocarcinoma and
           10-15 patients with any metastatic non-colorectal carcinoma that expresses either CEA or
           MUC-1. .

        -  The second cohort will enroll 12 patients with metastatic breast carcinoma and 14
           patients with metastatic ovarian carcinoma.

        -  All patients will receive the same vaccines on the same schedule. PANVAC(TM)-V
           (vaccinia) subcutaneously (s.c.) scheduled on day 1, followed by PANVAC(TM)-F (fowlpox)
           s.c. scheduled on days 15, 29, and 43 then every 28 days for up to 12 vaccines followed
           by every 3 months until disease progression or toxicity.

        -  Sargramostim (100 micro g) will be given at the site of the vaccination (PANVAC-V and
           PANVAC-F) on each vaccination day and for three consecutive days thereafter.

        -  Patients who have radiographic evidence of progressive disease, but who are otherwise
           clinically stable may revert back to monthly vaccinations.
    

Intervention name(s): PANVAC-V; PANVAC-F; Sargramostim (GM-CSF, Leukine)
Intervention type(s): Biological; Biological; Drug
Intervention description(s): Patients receive 2 x 10(8) pfu PANVAC-V (vaccinia) subcutaneously on Day 1.; Patients receive 1 x 10(9) pfu PANVAC-F (fowlpox) or about days 15, 29, and 43 then every month for 12 doses then every 3 months until disease progression or toxicity.; 100g sargramostim will be given subcutaneously at the site of the vaccination on each vaccination day and for three consecutive days thereafter.
Other intervention name(s): Granulocyte-macrophage colony-stimulating factor
Intervention MeSH terms: Molgramostim; Sargramostim
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: CEA; Vaccine; Immunotherapy; MUC-1; Cancer; Adenocarcinoma; Metastatic Adenocarcinoma