Clinical Trials /

Vaccine Therapy in Treating Patients With Metastatic Solid Tumors

NCT01376505

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Vaccine Therapy in Treating Patients With Metastatic Solid Tumors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: OSU-09138
  • SECONDARY ID: NCI-2011-00920
  • NCT ID: NCT01376505

Conditions

  • Malignant Solid Tumour
  • Breast Cancer
  • Malignant Tumor of Colon
  • GIST
  • Ovarian Cancer

Interventions

DrugSynonymsArms
HER-2 vaccineSynthetic peptides of HER-2 comprising B cell epitopes with a Promiscuous T cell epitope of Measles Virus.HER-2 Vaccine
Extension HER-2 vaccine trial at OBDEXTENSION HER-2 Vaccine at OBD

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.

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.

      OUTLINE: EXTENSION TRIAL AT OBD

      The dose-escalation (4 cohorts) has successfully completed with the accrual of 24 patients
      and the Optimum biological dose (OBD) has been determined as the dose at cohort level 2.

      The next phase of the study progresses directly into an extension trial at the OBD. 12
      patients will be accrued at that level. The extension cohort will be open to only HER-2
      and/or EGFR overexpressing cancers. Patients (all gastrointestinal,ovarian and breast must
      have received no more than three prior cytotoxic chemotherapy regimens in the last two years
      after standard therapy. Patients (breast, ovarian and gastrointestinal cancers) must have
      received no more than three prior cytotoxic chemotherapy regimens in the last two years after
      standard therapy.
    

Trial Arms

NameTypeDescriptionInterventions
HER-2 VaccineExperimentalcombination of MVF-HER-2 (597-626) and MVF-HER-2 (266-296) emulsified with nor-MDP and ISA 720 This escalation arm has completed. The trial has moved on to the extension arm
  • HER-2 vaccine
EXTENSION HER-2 Vaccine at OBDExperimentalCombination of MVF-HER-2 (597-626) and MVF-HER-2 (266-296) emulsified with nor-MDP and ISA 720 at dose level cohort 2 This extension arm is ongoing
  • Extension HER-2 vaccine trial at OBD

Eligibility 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

        ADDITIONAL KEY ELIGIBILITY CRITERIA FOR EXTENSION & EXPANSION COHORT:

          -  Histologically documented metastatic or unresectable breast, ovarian and
             gastrointestinal cancers

          -  Progressive disease after at least one line of standard therapy

          -  Patients must have received or refused first line standard systemic therapy for their
             metastases (if applicable)

          -  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 gastrointestinal cancers) must have received no more than three prior
             cytotoxic chemotherapy regimens in the last two years after standard therapy.

          -  Measurable disease, defined as ≥ 1 lesions that can be accurately measured in ≥ 1
             dimensions as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan

          -  Disease that is amenable to biopsy and be willing to undergo tumor biopsy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Type and duration of immune response measured over time to repeat vaccine administration
Time Frame:up to 6 months
Safety Issue:
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.

Secondary Outcome Measures

Measure:Evaluation of safety and toxicity at regular intervals by NCI common toxicity criteria (CTCAE v 4.0)
Time Frame:up to 6 months
Safety Issue:
Description: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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pravin Kaumaya

Trial Keywords

  • Vaccine Therapy

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