Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

Combined Vaccine Therapy in Treating Patients with Metastatic Solid Tumors

Protocol: OSU-09138

Full Title

Phase I Active Immunotherapy Trial with a combination of Two Chimeric (Trastuzumab-like and Pertuzumab-like) HER-2 B Cells Peptide Vaccine emulsified in ISA 720 and nor-MDP Adjuvant in Patients with Advanced Solid Tumors

Purpose

This phase I trial studies the side effects and best dose of a combined vaccine therapy and to see how well it works in treating patients with solid tumors that have spread to other parts of the body (metastatic). The cancer vaccine is made up of two proteins (that look like the tumor cells) mixed up with a special compound that may help train and boost the immune system to recognize and fight the tumor cells.

Study Objective

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 ISA 720. (Dose Escalation Phase)

II. To establish whether an optimal biological dose (OBD) of two combination vaccines is achieved. (Dose Escalation Phase)

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. (Dose Escalation Phase)

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. (Dose Escalation Phase)

V. To obtain preliminary estimates of efficacy of the combination of HER-2 vaccines in breast, ovarian and gastrointestinal cancers. (Expansion Phase)

VI. To characterize further the safety profile of immunization with combination of HER-2 epitopes. (Expansion Phase)

VII. To determine both humoral and cellular immune responses including the specificity, class and kinetics of anti-HER-2 peptide. (Expansion Phase)

SECONDARY OBJECTIVES:

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

II. To document any clinical responses that may occur. (Dose Escalation Phase)

III. To collect and analyze post-immune sera and peripheral blood cells for additional six months following the last injection. (Expansion Phase)

IV. To analyze serum biomarkers from cancer patients using Bio-Plex Suspension Array System. (Expansion Phase)

V. To analyze cytokines in response to vaccination. (Expansion Phase)

OUTLINE: This is a dose-escalation study.

Patients receive a HER2/neu peptide vaccine comprising measles virus fusion protein (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 and then every 1-2 months thereafter.

Are you eligible?

Inclusion Criteria:

For the dose escalation phase, patients must have histologically confirmed metastatic solid tumor; the malignancy should be considered incurable using standard treatment; for the extension cohort (N = 12) and for the expansion phase (N = 45), patients with advanced breast cancer (N = 15), advanced colorectal cancer (N = 15) and advanced ovarian cancer (N = 15) will be enrolled; all patients enrolled on the extension and expansion phase will be required to have measurable disease and a biopsy accessible site; patients are required to have both fresh tissue available before enrolling on the study; paraffin embedded tissue will also be obtained and used if available; in addition, all patients will also undergo optional post-treatment tumor biopsy at week 4

For both the extension and expansion cohorts, patients must have received or refused first line standard systemic therapy for their metastases (if applicable) and patients (pancreatic and esophageal cancers) must have received no more than two prior cytotoxic chemotherapy regimens in the last two years after standard therapy; patients (breast and gastrointestinalcolon cancers) must have received no more than three prior cytotoxic chemotherapy regimens in the last two years after standard therapy

Patients are not required to have HER-2 over-expression to be enrolled on this study at the dose escalation cohort; however, patients will be required to have HER-2 overexpression for the extension and expansion cohorts

If the patient has had HER-2 expression measured prior to enrollment, the report alone will be accepted on the expansion phase of the study

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; for the expansion phase, tissue will be made available the fresh biopsy

Patients are not required to have epidermal growth factor receptor (EGFR) over-expression to be on this study at the dose escalation cohort; however, patients will be required to have EGFR overexpression for the extension and expansion cohorts

If the patient has had EGFR expression measured prior to enrollment, the report alone will be accepted the dose escalation phase of the study

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; for the expansion phase, tissue will be made available the fresh biopsy

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

Absolute neutrophil count (ANC) >= 1,000/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 must be at least 3 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 uncontrolled 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; at the discretion of the treating physician, patients who show disease control for at least 6 months may be enrolled

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

Splenectomized patients

Patients with active autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, scleroderma, polymyositis dermato-myositis, or a vasculitic syndrome; at the discretion of the treating physician patients who show disease control for at least 6 months may be enrolled

Patients who have developed anaphylactic responses to other vaccines

Patients who have a history of congestive heart failure, coronary artery disease and myocardial infarction; active or unstable cardiovascular disease or cardiac disease requiring drug or device intervention

Breast Cancer Ovarian Cancer Gynecologic Cancers