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Vaccine Therapy in Treating Patients With Metastatic Solid Tumors

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ClinicalTrials.gov Identifier: NCT01376505
Recruitment Status : Recruiting
First Posted : June 20, 2011
Last Update Posted : July 26, 2019
Sponsor:
Information provided by (Responsible Party):
Pravin Kaumaya, Ohio State University Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE June 9, 2011
First Posted Date  ICMJE June 20, 2011
Last Update Posted Date July 26, 2019
Actual Study Start Date  ICMJE June 21, 2011
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 11, 2012)
  • Type and duration of immune response measured over time to repeat vaccine administration [ Time Frame: up to 6 months ]
    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 ]
    Will re-evaluate disease status with tumor markers and RESIST criteria,or full evaluation upon development of new symptoms
Original Primary Outcome Measures  ICMJE
 (submitted: June 16, 2011)
  • Type and duration of immune response measured over time to repeat vaccine administration [ Time Frame: Days 22, 43, 71 and 6 months ]
    Immune response will be defined by 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: 30 days after last vaccination and every 6 months ]
    Will re-evaluate disease status with tumor markers and RESIST criteria,or full evaluation upon development of new symptoms
Change History Complete list of historical versions of study NCT01376505 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 27, 2012)
Evaluation of safety and toxicity at regular intervals by NCI common toxicity criteria (CTCAE v 4.0) [ Time Frame: up to 6 months ]
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
Original Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2011)
Evaluation of safety and toxicity at regular intervals by NCI common toxicity criteria (CTCAE v 4.0) [ Time Frame: Day 1, 22, 43 and 6 month ]
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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vaccine Therapy in Treating Patients With Metastatic Solid Tumors
Official Title  ICMJE 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
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Malignant Solid Tumour
  • Breast Cancer
  • Malignant Tumor of Colon
  • GIST
  • Ovarian Cancer
Intervention  ICMJE
  • 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.
  • Biological: Extension HER-2 vaccine trial at OBD
    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. The dose level has been determined to be cohort 2. The combined vaccine preparation consists of 1.5mg of each of the HER-2 vaccine emulsified with nor-MDP (0.025) mg and Montanide ISA 720 will be administered in a final volume of 1.0 ml. Patients may also receive 6 months booster shots.
Study Arms  ICMJE
  • Experimental: HER-2 Vaccine

    combination 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

    Intervention: Biological: HER-2 vaccine
  • Experimental: EXTENSION HER-2 Vaccine at OBD

    Combination 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

    Intervention: Biological: Extension HER-2 vaccine trial at OBD
Publications * Bekaii-Saab T, Wesolowski R, Ahn DH, Wu C, Mortazavi A, Lustberg M, Ramaswamy B, Fowler J, Wei L, Overholser J, Kaumaya PTP. Phase I Immunotherapy Trial with Two Chimeric HER-2 B-Cell Peptide Vaccines Emulsified in Montanide ISA 720VG and Nor-MDP Adjuvant in Patients with Advanced Solid Tumors. Clin Cancer Res. 2019 Jun 15;25(12):3495-3507. doi: 10.1158/1078-0432.CCR-18-3997. Epub 2019 Feb 25.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 24, 2019)
100
Original Estimated Enrollment  ICMJE
 (submitted: June 16, 2011)
36
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 with ICH of 0
  • Patients on targeted therapies, such as Cycline Dependent Kinase (CDK) 4/6 or mammalian target of rapamycin (mTOR) inhibitors in combination with endocrine therapy.
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pravin Kaumaya, PhD 614-292-7028 pravin.kaumaya@osumc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01376505
Other Study ID Numbers  ICMJE OSU-09138
NCI-2011-00920 ( Registry Identifier: Clinical Trial Reporting Program )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Pravin Kaumaya, Ohio State University Comprehensive Cancer Center
Study Sponsor  ICMJE Pravin Kaumaya
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Pravin Kaumaya, PhD Ohio State University
PRS Account Ohio State University Comprehensive Cancer Center
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP