Vaccine Therapy in Treating Patients With Metastatic Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Ohio State University Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
Pravin Kaumaya, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01376505
First received: June 9, 2011
Last updated: June 27, 2014
Last verified: June 2014
  Purpose

This phase I trial studies the side effects and best dose of vaccine therapy in treating patients with metastatic solid tumors. Vaccines made from antibodies and peptides combined with tumor cells may help the body build an effective immune response to kill tumor cells.


Condition Intervention Phase
Malignant Solid Tumour
Breast Cancer
Malignant Tumor of Colon
GIST
Ovarian Cancer
Biological: HER-2 vaccine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Type and duration of immune response measured over time to repeat vaccine administration [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
    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.

  • Clinical benefit will be assessed [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
    Will re-evaluate disease status with tumor markers and RESIST criteria,or full evaluation upon development of new symptoms


Secondary Outcome Measures:
  • Evaluation of safety and toxicity at regular intervals by NCI common toxicity criteria (CTCAE v 4.0) [ Time Frame: up to 6 months ] [ Designated as safety issue: Yes ]
    Safety will be defined if patients are able to receive all 3 vaccinations without dose-limiting toxicity (DLT), any incidence of grade 3 hematologic and non-hematologic toxicity or any incidence of Grade 4 toxicity. The development of a positive skin test to the vaccine immediate hypersensitivity


Estimated Enrollment: 36
Study Start Date: June 2011
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HER-2 Vaccine
combination of MVF-HER-2 (597-626) and MVF-HER-2 (266-296) emulsified with nor-MDP and ISA 720
Biological: HER-2 vaccine
Three intramuscular (IM) injections (separated by 21 days) of a mixture of two peptides {MVF-HER-2(597-626) and MVF-HER-2 (266-296)} vaccine emulsified with nor-MDP in ISA 720 vehicle. Increasing doses of the combined vaccine preparation emulsified with nor-MDP (0.025) mg and Montanide ISA 720 will be administered in a final volume of 1.0 ml. Starting at dose level 1, 1.0mg of each peptide will be used for vaccination. In increasing dosing cohorts 1.5mg, 2.0mg and 2.5mg will be used. Patients may also receive 6 months booster shots.
Other Name: Synthetic peptides of HER-2 comprising B cell epitopes with a Promiscuous T cell epitope of Measles Virus.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01376505

Contacts
Contact: Tanios Bekaii-Saab, MD 614-293-9863 Tanios.Bekaii-Saab@osumc.edu
Contact: Pravin Kaumaya, PhD 614-292-7028 pravin.kaumaya@osumc.edu

Locations
United States, Ohio
Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Pravin Kaumaya, PhD    614-292-7028    Pravin.Kaumaya@osumc.edu   
Contact: Tanios Bekaii-Saab, MD    614-293-9863    Tanios.Bekaii-saab@osumc.edu   
Sub-Investigator: William Carson, MD         
Sponsors and Collaborators
Pravin Kaumaya
Investigators
Principal Investigator: Pravin Kaumaya, PhD Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: Pravin Kaumaya, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01376505     History of Changes
Other Study ID Numbers: OSU-09138, NCI-2011-00920
Study First Received: June 9, 2011
Last Updated: June 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Ohio State University Comprehensive Cancer Center:
Vaccine Therapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Colonic Neoplasms
Ovarian Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on July 23, 2014