Vaccination of High Risk Breast Cancer Patients

Study Overview
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Brief Summary
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Objective - Determine the safety and tolerability of a peptide mimotope-based vaccine upon immunization of breast cancer subjects.

Detailed Description
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After signing Institutional Review Board (IRB) approved consent, cohorts of 3-6 stage IV breast cancer subjects will be enrolled into the study. The vaccine doses will be prepared and dispensed by the University of Arkansas for Medical Sciences (UAMS) Pharmacy following the manufacturer's instructions. Subjects will receive 1.0 mL subcutaneous (SC) injections of the vaccine on 5 separate occasions during Weeks 1, 2, 3, 7, and 19. The first cohort will begin with the 300 mg dose, and then the subsequent cohorts will escalate to 500 mg or de-escalate to 100 mg as determined by the toxicity criteria. The immunization at week 19 is considered a booster immunization. The vaccine will be administered at rotating sites on the limbs or abdomen. The study will last for approximately 12 - 24 months.

Official Title
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Phase 1 Safety Study of a Carbohydrate Mimotope Based Vaccine With MONTANIDE ISA 51 VG Adjuvant

Conditions
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Stage IV Breast Cancer

Intervention / Treatment
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* Biological: Vaccination with Mimotope P10s-PADRE/MONTANIDE ISA 51 VG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects of all races with histologically or cytologically confirmed stage IV breast cancer are eligible. The cancer may be newly diagnosed metastatic or relapsed after primary or adjunctive therapy and must not have required a treatment change for 2 months. Treatments with anti-estrogen therapy or chemotherapy are allowed. The chemotherapy regimen cannot contain steroids in the pre or post supportive care medications. If a subject is on an investigational drug, the drug must be cleared from the body over a period of 4 weeks. Disease staging will be done according to the American Joint Commission on Cancer (AJCC), sixth edition. Age 18 years and older of all races and ethnicity. ECOG Performance Status 0 or 1. Subjects must not have an active infection requiring treatment with antibiotics. Subjects must not have other significant medical, surgical or psychiatric conditions, or require any medication or treatment, which may interfere with compliance of the treatment regimen. Subjects must not have a diagnosis or evidence of organic brain syndrome, significant impairment of basal cognitive function or any psychiatric disorder that might preclude participation in the full protocol. Subjects must have no other current malignancies. Subjects with prior history at any time of any in situ cancer, including lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or Clark I melanoma in situ or basal or squamous skin cancer are eligible, provided they are disease-free at the time of registration. Subjects with other malignancies are eligible if they have been continuously disease free for ≥ 5 years prior to the time of registration. Subjects must not have autoimmune disorders or conditions of immunosuppression. This includes, but is not limited to being treated with corticosteroids, including oral steroids (i.e. prednisone, dexamethasone), continuous use of topical steroid creams or ointments or any steroid-containing inhalers. Subjects who have been on systemic steroids will require a 6-week washout period. Subjects who discontinue the use of these classes of medication for at least 6 weeks prior to registration are eligible if, in the judgment of the treating physician, the subject is not likely to require these classes of drugs during the treatment period. Replacement doses of steroids for subjects with adrenal insufficiency are allowed. Women of childbearing potential must not be pregnant (negative serum pregnancy test must be done 48 hours prior to receiving the first dose of study drug) or breastfeeding,due to the unknown effects of peptide/mimotope vaccines on a fetus or infant. Women of childbearing potential must be counseled to use an accepted and effective method of contraception (including abstinence) while on treatment and for a period of 18 months after completing or discontinuing treatment. Accepted methods include oral contraceptives, barrier method, Intrauterine Devices (IUDs), and abstinence. Subjects must have obtained a white blood cell (WBC) count ≥ 3,000/mm3 and platelet count ≥ 100,000/mm3 within 2 weeks prior to registration. Subjects must have a serum glutamic-oxaloacetic transaminase (SGOT)/aspartate aminotransferase test (AST) and bilirubin ≤ 2 x institutional upper limit (IUL) of normal and serum creatinine ≤ 1.8 mg/dl, all obtained within 2 weeks prior to registration. Subjects must be immunocompetent as measured by responsiveness to two recall antigens by skin testing. All subjects who wish to participate in the study must sign an informed consent approved by the UAMS Institutional Review Board (IRB). Laboratory tests must be completed within 2 weeks before the first dose.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Initial Cohort<br>Vaccination with Mimotope P10s-PADRE/MONTANIDE ISA 51 VG Subcutaneous administration 5 doses of 300 micrograms | Biological: Vaccination with Mimotope P10s-PADRE/MONTANIDE ISA 51 VG<br>* All research participants will receive the Mimotope P10s-PADRE/MONTANIDE ISA 51 VG vaccine via subcutaneous (SC) injection following the schedule<br>|
| Active Comparator: Escalation Cohort<br>Vaccination with Mimotope P10s-PADRE/MONTANIDE ISA 51 VG Subcutaneous administration of 5 doses of 500 micrograms | Biological: Vaccination with Mimotope P10s-PADRE/MONTANIDE ISA 51 VG<br>* All research participants will receive the Mimotope P10s-PADRE/MONTANIDE ISA 51 VG vaccine via subcutaneous (SC) injection following the schedule<br>|
| Active Comparator: De-escalation Cohort<br>Vaccination with Mimotope P10s-PADRE/MONTANIDE ISA 51 VG Subcutaneous administration of 5 doses of 100 micrograms | Biological: Vaccination with Mimotope P10s-PADRE/MONTANIDE ISA 51 VG<br>* All research participants will receive the Mimotope P10s-PADRE/MONTANIDE ISA 51 VG vaccine via subcutaneous (SC) injection following the schedule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Dose-limiting Toxicity (Defined as an Adverse Event of Grade 3 or Higher) | The safety and tolerability of the P10s-PADRE/MONTANIDE ISA51 VG vaccine will be determined by toxicity assessments throughout the duration of the study. Subjects will be evaluated for toxicity using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. | 9 weeks per subject |