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Phase I Active Immunotherapy Trial With a Combination of Two Chimeric (Trastuzumab-like and Pertuzumab-like)Human Epidermal Growth Factor Receptor 2 (HER-2) B Cell Peptide Vaccine Emulsified in ISA 720 and Nor-MDP Adjuvant in Patients With Advanced Solid Tumors


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Malignant Solid Tumour, Breast Cancer, Malignant Tumor of Colon, GIST, Ovarian Cancer

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Trial Information

Phase I Active Immunotherapy Trial With a Combination of Two Chimeric (Trastuzumab-like and Pertuzumab-like)Human Epidermal Growth Factor Receptor 2 (HER-2) B Cell Peptide Vaccine Emulsified in ISA 720 and Nor-MDP Adjuvant in Patients With Advanced Solid Tumors


PRIMARY OBJECTIVES:

I. To perform early phase clinical trial assessing safety and clinical toxicity of
immunization, and as well as to establish an optimal biological dose (OBD) of combination
vaccines with n-muramyldipeptide derivative (nor-MDP) as adjuvant emulsified in Montanide
(ISA 720).

II. To establish whether an OBD of two combination vaccines is achieved. III. To measure
both humoral and cellular immune responses including the specificity, class and kinetics of
anti-human epidermal growth factor receptor-2 (HER-2) peptide.

IV. To evaluate whether the combination of HER-2 epitopes show therapeutic benefit, provide
synergistic and/or additive effects and to enumerate mechanisms of action.

SECONDARY OBJECTIVES:

I. To collect and analyze post-immune sera and peripheral blood cells for additional six
months post the last injection.

II. To document any clinical responses that may occur.

OUTLINE: This is a dose-escalation study.

Patients receive a HER2/neu peptide vaccine comprising measles virus epitope MVF-HER-2
(266-296) and MVF-HER-2 (597-626) emulsified with nor-MDP in ISA 720 intramuscularly (IM) on
day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.


Inclusion Criteria:



- Must have histologically confirmed metastatic solid tumor; the malignancy should be
considered incurable using standard treatment

- Patients are not required to have HER-2 over-expression to be on this study

- If the patient has had HER-2 expression measured prior to enrollment, the report
alone will be accepted

- If the patient has not had HER-2 expression measured prior to enrollment on this
study tumor tissue blocks and/or freshly isolated tissue must be available for
determination of HER-2 expression

- Patients are not required to have epidermal growth factor receptor (EGFR)
over-expression to be on this study

- If the patient has had EGFR expression measured prior to enrollment, the report alone
will be accepted

- If the patient has not had EGFR expression measured prior to enrollment on this study
tumor tissue blocks and/or freshly isolated tissue must be available for
determination of EGFR expression

- Patients with prior history of treated brain metastases who are off steroids and have
stable metastatic brain disease for at least 3 months are eligible

- Patients must be ambulatory with an Eastern Cooperative Oncology Group (ECOG)
performance status of 0, 1, or 2

- White blood cells > 3500/mm^3

- Platelet count > 100,000/mm^3

- Serum bilirubin < 1.5 mg %, regardless of whether patients have liver
involvement secondary to tumor

- Alanine aminotransferase (ALT) must be < 2 times upper limit of normal

- Creatinine < 1.5 mg/dL or calculated creatinine clearance > 60 mL/min

- Patients will be tested for reactivity to a panel of four common microbial skin test
antigens: candida, trichophyton, intermediate strength purified protein derivative
(PPD), and tetanus toxoid; determination of patient eligibility for this trial will
proceed independently of these skin test results; patients who have previously been
tested for these antigens but were excluded from participation in the trial due to
non-reactivity may be considered as eligible provided that all other eligibility
criteria are met

- Patients must be at least 4 weeks past any prior surgery, cytotoxic, chemotherapy,
other immunotherapy, hormonal therapy, or radiation therapy; patients having been
treated with monoclonal antibodies may enter the trial after a specified period of
time (2 times the mean half life of the agent); patients must have recovered from any
toxicity of prior therapy prior to enrolling on study except for neuropathy where
patients need to recover to less than grade 2

- Women of child-bearing potential must not be pregnant and must have a negative
pregnancy test; men and women must agree to practice effective contraception while on
this study

- Patients must obtain a base line Echocardiogram or multi gated acquisition scan
(MUGA) and require the left ventricular ejection fraction to be within normal limits
(or 50% or higher)

- Ability to understand and the willingness to sign a written informed consent
document; the patient must be aware that his/her disease is neoplastic in nature and
willingly consent after being informed of the procedure to be followed, the
experimental nature of the therapy, alternatives, potential benefits, side-effects,
risks, and discomforts

Exclusion Criteria:

- Patients who are {MVF-HER-2(266-296) and MVF-HER-2 (597-626)} immediate
hypersensitivity skin test positive

- Patients who have evidence of active infection that requires antibiotic therapy;
patients must have been off antibiotic treatment for at least 3 weeks prior to
initiating treatment and must be confirmed to be clear of the infection; if patient
develops an infection requiring antibiotic treatment while on the treatment portion
of the study patients will be treated for the active infection with antibiotics and
will resume vaccine treatment when the infection is healed

- Patients with known active human immunodeficiency virus (HIV), hepatitis A, hepatitis
B, or hepatitis C infection

- Patients with serious cardiopulmonary disorders, including congestive heart failure,
symptomatic coronary artery disease, serious cardiac arrhythmia, and symptomatic
chronic obstructive pulmonary disease or patients with other serious uncontrolled
medical diseases

- Patients who require or likely to require corticosteroids or other immunosuppressives
for intercurrent disease are NOT eligible

- Splenectomized patients

- Autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus,
scleroderma, polymyositis dermatomyositis, or a vasculitic syndrome

- Patients who have developed anaphylactic responses to other vaccines

- History of congestive heart failure, coronary artery disease and myocardial
infarction; active or unstable cardiovascular disease or cardiac disease requiring
drug or device intervention

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Type and duration of immune response measured over time to repeat vaccine administration

Outcome Description:

Immune response will be defined by Enzyme-linked immunosorbent assay (ELISA), Flow cytometry, T-cell proliferation and cytokine. The magnitude of antibody levels will be assessed to the vaccine and HER-2 over-expressing cells (e.g.,BT474). Lymphoproliferative responses will be assessed by a non radioactive cell proliferation assay Bioplex human isotyping kit will be used to assess antibody types and cytokine profiles.

Outcome Time Frame:

up to 6 months

Safety Issue:

No

Principal Investigator

Pravin Kaumaya, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University

Authority:

United States: Food and Drug Administration

Study ID:

OSU-09138

NCT ID:

NCT01376505

Start Date:

June 2011

Completion Date:

Related Keywords:

  • Malignant Solid Tumour
  • Breast Cancer
  • Malignant Tumor of Colon
  • GIST
  • Ovarian Cancer
  • Vaccine Therapy
  • Breast Neoplasms
  • Neoplasms
  • Colonic Neoplasms
  • Ovarian Neoplasms

Name

Location

Ohio State University Medical CenterColumbus, Ohio  43210