Docetaxel Alone or in Combination With Vaccine to Treat Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will test whether giving a combination of a vaccine together with docetaxel is
      more effective against breast cancer than docetaxel alone. The Food and Drug Administration
      has approved docetaxel to treat many cancers, including breast cancer. The vaccine consists
      of three parts: 1) a "priming vaccine" called PANVAC (PAN (all) VAC (vaccine)) trademark
      [TM]-V, which is made from vaccinia virus; 2) a "boosting vaccine" called PANVAC[TM]-F, made
      from fowlpox virus; and 3) sargramostim, or granulocyte macrophage colony stimulating factor
      (GM-CSF), a protein that may help boost the immune system. Human genes are inserted into the
      vaccinia and fowlpox viruses to cause production of carcinoembryonic antigen (CEA) and mucin
      1 (MUC-1)-two proteins that are often produced by cancer cells and can be used as a target
      for the immune system to attack the cancer. Another type of deoxyribonucleic acid (DNA) is
      inserted to cause production of other proteins that enhance immune activity.

      Patients 18 years of age or older with metastatic breast cancer (disease that has spread
      beyond the original site) and whose cancer produces CEA or mucin 1 (MUC-1) protein may be
      eligible for this study. Patients must have antigen type human leukocyte antigen A2 (HLA-A2).
      They may have received adjuvant docetaxel treatment at least 3 months before entering this
      study, prior hormonal therapy and up to three chemotherapy regimens. Candidates are screened
      with a medical history and physical examination, blood and urine tests, electrocardiogram,
      and computerized tomography (CT) or magnetic resonance imaging scans.

      Participants are randomly assigned to one of two treatment groups - docetaxel alone or
      docetaxel plus vaccine - as follows:

      Docetaxel Alone

      All patients receive docetaxel. The drug is infused through a vein over 30 to 60 minutes once
      a week for 3 consecutive weeks with 1 week off drug. Patients also take dexamethasone 12
      hours and 1 hour before and 12 hours after the docetaxel to help prevent fluid retention
      (edema) that docetaxel may cause.

      Docetaxel Plus Vaccine

      Participants receive the priming vaccination followed by monthly boosting vaccinations, along
      with the weekly docetaxel therapy. With every vaccination, patients also receive an injection
      of sargramostim to increase the number of immune cells at the vaccination site. Sargramostim
      injections are given the day of vaccination and daily for the next 3 days. All vaccine and
      sargramostim doses are given as injections under the skin, usually in the thigh. Patients are
      observed in the clinic for 1 hour after each injection.

      Patients have blood tests every four weeks to monitor drug side effects and before every
      vaccination to check blood counts. A bone scan or CT scan (or both) is done every 2 to 3
      months to check the response to treatment.

      Patients may continue receiving treatment as long as their disease does not worsen and they
      can tolerate the treatment without significant side effects. Patients assigned to receive
      docetaxel alone whose disease progresses after 3 months on the drug may choose to receive the
      vaccine or come off the study to receive other treatment options. Patients are monitored with
      yearly telephone calls for up to 15 years.
    

Detailed description: 
      Background:

      Weekly docetaxel therapy is currently used as a standard treatment for patients with
      metastatic breast cancer.

      Although many patients initially respond to this form of therapy, the majority will
      eventually develop disease progression and die from their disease.

      We have explored the use of combining pox vector vaccines with docetaxel. In a recent
      clinical trial, men with prostate cancer were given both the vaccine and docetaxel without
      any significant toxicity and the docetaxel did not diminish immune responses to the vaccine.

      Objectives:

      To evaluate progression free survival comparing PANVAC + docetaxel vs. docetaxel alone in
      patients with metastatic breast cancer.

      To evaluate overall survival comparing PANVAC + docetaxel vs. docetaxel alone in patients
      with metastatic breast cancer.

      To evaluate in both arms cluster of differentiation 8 (CD8+) T cell responses directed
      against carcinoembryonic antigen (CEA) and mucin (MUC-1) in human leukocyte antigen 2
      (HLA-A2), A3, and A24 positive patients by interferon-gamma enzyme linked immunosorbent spot
      (ELISPOT) assay.

      Eligibility:

      Metastatic breast cancer (either male or female) with evidence of metastatic disease (must
      have radiographic evidence of disease) and life expectancy of at least 4 months.

      Patients may have received unlimited prior hormonal therapy or chemotherapy, but no prior
      docetaxel for metastatic disease.

      Hematological eligibility parameters within 16 days of starting therapy:

      Granulocyte count greater than or equal to 1,500/mm^3, Platelet count greater than or equal
      to 100,000/mm^3, hemoglobin (Hgb) greater than or equal to 8 Gm/dL.

      Design:

      A randomized Phase II study evaluating the role of combining docetaxel with PANVAC[TM]-V
      (recombinant vaccinia containing the genes encoding for CEA, MUC-1, lymphocyte
      function-associated antigen 3 (LFA-3), intercellular adhesion molecule 1 (ICAM-1) and B7.1)
      and PANVAC[TM]-F (recombinant fowlpox containing the genes encoding for CEA, MUC-1, LFA-3,
      ICAM-1 and B7.1) vs. docetaxel alone to determine if the addition of the vaccine can prolong
      the time to disease progression as well as overall survival in patients with metastatic
      breast cancer.

      Patients randomized to docetaxel alone may receive sequential therapy with PANVAC[TM]-V and
      PANVAC[TM]-F at time of disease progression.

      In patients randomized to the concurrent therapy, PANVAC[TM]-V will be administered to
      patients 3 weeks prior to the start of chemotherapy as the initial vaccine.

      The immune responses to CEA and MUC-1 will then be boosted by administration of PANVAC[TM]-F.

      Sargramostim or granulocyte macrophage colony stimulating factor (GM-CSF) will be
      administered with each vaccine inoculation for four consecutive days only for patients
      treated at the National cancer Institute (NCI).
    

Intervention name(s): Docetaxel; PANVAC-V; PANVAC-F; Sargramostim
Intervention type(s): Drug; Biological; Biological; Biological
Intervention description(s): 35 mg/m^2 intravenous 30-60 minutes once a week for 3 consecutive weeks with 1 week off drug.; 2 x 10^8 PFU; 1 x 10^9 PFU; Given subcutaneously under the skin, usually in the thigh on the day of vaccination and daily for the next 3 days.
Other intervention name(s): Taxotere; GM-CSF
Intervention MeSH terms: Docetaxel; Sargramostim
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: CEA; MUC-1; Immunotherapy; GM-CSF; Vaccine; Breast Cancer; Metastatic Breast Cancer