This 2-phase study will determine the safety of treating patients with breast cancer with
the genetically engineered HyperAcute-Breast cancer vaccine. It will establish the proper
vaccine dose and will examine side effects and potential benefits of the treatment. The
vaccine contains killed breast cancer cells containing a mouse gene that causes the
production of a foreign pattern of protein-sugars on the cell surface. It is hoped that the
immune response to the foreign substance will stimulate the immune system to attack the
patient's own cancer cells that have similar proteins without this sugar pattern, causing
the tumor to remain stable or shrink.
Patients 18 years of age or older with breast cancer that has recurred or no longer responds
to standard treatment may be eligible for this study. Candidates will be screened with
medical history and physical examination, blood tests, urinalysis, chest x-rays and CT
scans. MRI, PET, and ultrasound scans may be obtained if needed.
Participants will receive four vaccinations a month apart from each other. The vaccines
will be injected under the skin, similar to the way a tuberculosis skin test is given.
Phase I of the study will treat successive groups of patients with increasing numbers of the
vaccine cells to evaluate side effects of the treatment and determine the optimum dose.
Phase II will look for any beneficial effects of the vaccine given at the highest dose found
to be safe in Phase I. Weekly blood samples will be drawn during the 4 months of vaccine
treatment. In addition, patient follow-up visits will be scheduled every 2 months for the
first year after vaccination and then every 3 months for the next 2 years for the following
tests and procedures to evaluate treatment response and side effects:
- Medical history and physical examination
- Blood tests
- X-rays and various scans (nuclear medicine/CT/MRI)
- FACT-B Assessment questionnaire to measure the impact of treatment on the patient's
general well-being. The questionnaire is administered before beginning treatment,
before each vaccination, and during follow-up visits after completing the treatment.
It includes questions on the severity of breast cancer symptoms and the ability to
perform normal activities of daily life.
According to 2002 statistics of the American Cancer Society, an estimated 203,500
individuals will be diagnosed with breast cancer and 39,600 will die of the disease this
year despite all current therapy. This protocol attempts to exploit an approach to breast
cancer gene therapy using a naturally occurring barrier to xenotransplantation in humans in
attempt to vaccinate patients against their breast cancer. The expression of the murine
alpha (1,3) galactosyltransferase [alpha (1,3) GT] gene results in the cell surface
expression of alpha (1,3) galactosyl-epitopes (alpha-gal) on membrane glycoproteins and
glycolipids. These epitopes are the major target of the hyperacute rejection response that
occurs when organs are transplanted from non-primate donor species into man. Human hosts
often have pre-existing anti-alpha-gal antibodies that bind alpha-gal epitopes and lead to
rapid activation of complement and cell lysis. The pre-existing anti-alpha-gal antibodies
found in most individuals are thought to be due to exposure to alpha-gal epitopes that are
naturally expressed on normal gut flora leading to chronic immunological stimulation. These
antibodies may comprise up to 1% of serum IgG. In this Phase I/II trial, patients with
relapsed or refractory breast cancer will undergo a series of four intradermal injections
with a vaccine composed of irradiated allogeneic breast cancer cell lines (HAB-1 and HAB-2)
that have been transduced with a recombinant Moloney murine leukemia virus (MoMLV)-based
retroviral vector expressing the murine alpha (1,3) GT gene. Endpoints of the study include
determination of dose-limiting toxicity (DLT), maximum tolerated dose (MTD), tumor and
- Histological diagnosis of infiltrating breast carcinoma, including infiltrating
ductal carcinoma, lobular carcinoma, medullary carcinoma, colloid, comedocarcinoma,
papillary, inflammatory carcinoma, signet ring carcinoma. The patient's pathology
must be reviewed and confirmed by Iowa Methodist Medical Center's or Mercy Medical
Center's Pathology Department.
- AJCC Stage IV (any T, any N, M1), metastatic, progressive or recurrent breast
carcinoma. Patients may not be eligible for other curative intent treatment (e.g.
surgical resection). Patients must have failed one salvage treatment.
- Eastern Cooperate Oncology Group Performance Status less than or equal to 2.
- Serum albumin greater than or equal to 3.0 gm/dL.
- Expected survival greater than or equal to 6 months.
- Subjects must have a negative serology for Hep B, C and HIV prior to entering study.
- Adequate organ function including: Marrow: Hemoglobin greater than or equal to 10.0
mg/dL, absolute granulocyte count (AGC) greater than or equal to 1,500/mm(3),
platelets greater than or equal to 100,000/mm(3), absolute lymphocyte count greater
than or equal to 475/mm(3). Hepatic: serum total bilirubin less than or equal to 1.5
x upper limit of normal (ULN), ALT (SGPT) and AST (SGOT) less than or equal to 2.5 x
ULN. Renal: serum creatinine less than or equal to 1.5 x ULN or creatinine clearance
greater than or equal to 50 mL/min.
- All on-study tests must be less than or equal to Grade I toxicity for patient to be
eligible for study, excluding serum LDH levels. PT, PTT must be less than or equal to
1.5 x ULN except for patients who are on therapeutic anticoagulant therapy.
- Measurable or non-measurable disease as defined as:
Measurable - those that can be accurately measured in at least one dimension (longest
diameter to be recorded) as greater than or equal to 20 mm with conventional techniques
(CT, MRI, x-ray) or as greater than or equal to 10 mm with spiral CT scan. All tumor
measurements must be recorded in millimeters (or decimal fractions of centimeters).
Non-measurable - All other lesions (or sites of disease), including small lesions (longest
diameter less than 20 mm with conventional techniques or less than 10 mm using spiral CT
scan), are considered non-measurable disease. Bone lesions, leptomeningeal disease,
ascites, pleural or pericardial effusions, lymphangitis cutis or pulmonis, inflammatory
breast disease, abdominal masses (not followed by CT or MRI), and cystic lesions are all
- Prior therapy for breast cancer that may include surgery, radiation therapy, and/or
less than or equal to 2 different cytotoxic chemotherapy regimens (including
neoadjuvant and adjuvant treatment). Patients receiving preoperative (neoadjuvant)
and postoperative (within 12 weeks of surgery) adjuvant chemotherapy with the same
agent(s) will be considered to have received a single chemotherapy regimen.
Patients with previously treated, unresponsive or progressive disease that have failed at
least one salvage regimen.
- Patients must be greater than or equal to 4 weeks since major surgery, radiotherapy,
chemotherapy (6-weeks if they were treated with a nitrosourea or mitomycin) and
recovered from the toxicity of prior treatment to less than or equal to Grade 1,
exclusive of alopecia or fatigue.
- Patients must have the ability to understand the study, its risks, side effects,
potential benefits and is able to give written informed consent to participate.
Patients may not be consented by a durable power of attorney (DPA).
- Male and female subjects of child producing potential must agree to use contraception
or avoidance of pregnancy measures while enrolled on study and receiving the
experimental drug, and for one month after the last immunization.
- Age less than 18-years-old.
- Active CNS metastases or carcinomatous meningitis.
- Hypercalcemia greater than 2.9 mmol/L, unresponsive to standard therapy (e.g., I.V.
hydration, diuretics, calctonin and/or bisphosphate therapy).
- Pregnant or nursing women due to the unknown effects of vaccination on the developing
fetus or newborn infant.
- Other malignancy within five years, unless the probability of recurrence of the prior
malignancy is less than 5%. Patient's curatively treated for squamous and basal cell
carcinoma of the skin and carcinoma in situ of the uterine cervix (CIN) or patients
with a history of malignant tumor in the past that have been disease free for at
least five years are also eligible for this study.
- History of organ transplant or current active immunosuppressive therapy (such as
cyclosporine, tacrolimus, etc.) or history of prior immunotherapy except Herceptin
and/or other monoclonal antibody therapies.
- Subjects taking systemic corticosteroid therapy for any reason including replacement
therapy for hypoadrenalism, are not eligible. Subjects receiving inhaled or topical
corticosteroids are eligible. Subjects who require systemic corticosteroids after
beginning vaccinations, will be removed from the study.
- Significant or uncontrolled congestive heart failure (CHF), myocardial infarction,
significant ventricular arrhythmias within the last six months or significant
- Active infection or antibiotics within 1-week prior to study, including unexplained
fever (temp. greater than 38.1 degrees Celsius).
- Autoimmune disease (e.g., systemic lupus erythematosis, active rheumatoid arthritis,
etc). Patients with a remote history of asthma or mild active asthma are eligible.
- Other serious medical conditions that may be expected to limit life expectancy to
less than 2 years (e.g., liver cirrhosis).
- Any condition, psychiatric or otherwise, that would preclude informed consent
consistent follow-up or compliance with any aspect of the study (e.g., untreated
schizophrenia or other significant cognitive impairment, etc).
- A known allergy to any component of the alpha (1,3) galactosyltransferase tumor
vaccine or cell lines from which it is derived.
- Patients having undergone splenectomy.