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Trial record 1 of 1 for:    02204098
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Safety and Immune Response to a Mammaglobin-A DNA Vaccine In Breast Cancer Patients Undergoing Neoadjuvant Endocrine Therapy

This study is currently recruiting participants.
Verified July 2017 by Washington University School of Medicine
Sponsor:
ClinicalTrials.gov Identifier:
NCT02204098
First Posted: July 30, 2014
Last Update Posted: July 19, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Washington University School of Medicine
  Purpose
The purpose of this research study is to find out about the safety of injecting the gene (DNA) for mammaglobin-A into people with breast cancer. The DNA used in this study was purified from bacteria and contains the gene for mammaglobin-A. Mammaglobin-A is a protein that is highly expressed by breast cancer cells. Injection of mammaglobin-A DNA may be a way to generate an immune response to breast cancer cells. There is evidence that an immune response may be a way to fight cancer. In addition to evaluating the safety of the mammaglobin-A injection, this study is also looking at the immune response that the participant's body has after each injection.

Condition Intervention Phase
Breast Cancer Breast Carcinoma Malignant Neoplasm of Breast Biological: Mammaglobin-A DNA Vaccine Drug: Anastrozole Drug: Letrozole Drug: Tamoxifen Drug: Exemestane Drug: Goserelin Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1B Randomized Clinical Trial to Evaluate the Safety and Immune Response to a Mammaglobin-A DNA Vaccine in Breast Cancer Patients Undergoing Neoadjuvant Endocrine Therapy

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Safety [ Time Frame: Day 126 (+/- 7days) ]

    Assessment of plasmid DNA safety will include both clinical observation and laboratory evaluation. Safety will be closely monitored after injection with eight or more clinical and laboratory assessments in the first 24 weeks of the trial. The following parameters will be assessed following vaccination:

    1. Local signs and symptoms
    2. Systemic signs and symptoms
    3. Laboratory evaluations, including blood counts and serum chemistries
    4. Adverse and serious adverse events

    Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0



Secondary Outcome Measures:
  • Immune response [ Time Frame: Week 52 ]
    ELISPOT analyses and intracellular cytokine expression analyses using multi-parameter flow cytometry, and peptide MHC tetramer analyses will be performed. Peripheral blood will be obtained at two independent time points before vaccination (Pre-study, and Day 28 +/- 7 days), and at four independent time points following vaccination (Day 56 +/- 7 days, Day 84 +/- 7 days, Day 112 +/- 7 days, and Day 365 +/- 28 days).

  • Objective tumor response rate (ORR) [ Time Frame: 5 years ]

    -ORR=complete response (CR) + partial response (PR)

    • Complete response: disappearance of all lesions and normalization of tumor marker level
    • Partial response: at least a 30% decrease in the sum of the diameters of target lesions and no new lesions

  • Progression-free survival (PFS) [ Time Frame: 5 years ]
    ◦Progressive disease - At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, appearance of one more new lesions PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

  • Overall survival (OS) [ Time Frame: 5 years ]

Estimated Enrollment: 60
Actual Study Start Date: January 7, 2015
Estimated Study Completion Date: October 31, 2024
Estimated Primary Completion Date: February 28, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: Endocrine Therapy & Mammaglobin-A DNA Vaccine

Participants will be treated with neoadjuvant endocrine therapy, with the dose and agent to be determined by the treating physician

The schedule of vaccination is day 28 ± 7, day 56 ± 7 and day 84 ± 7 with at least 21 days between injection days.

All study injections will be given intramuscularly using an integrated electroporation administration system.

At each vaccination timepoint, patients will receive two injections of the mammaglobin-A DNA vaccine, one injection into each deltoid or lateralis.

Biological: Mammaglobin-A DNA Vaccine Drug: Anastrozole

Anastrozole is in a class of drugs called nonsteroidal aromatase inhibitors and is considered endocrine therapy.

The treating physician will decide what type and dose of endocrine therapy the participant will receive.

Other Name: Arimidex
Drug: Letrozole

Letrozole is in a class of drugs called nonsteroidal aromatase inhibitors and is considered endocrine therapy.

The treating physician will decide what type and dose of endocrine therapy the participant will receive.

Other Name: Femara
Drug: Tamoxifen

Tamoxifen is in a class of drugs called selective estrogen receptor modulators and is considered endocrine therapy.

The treating physician will decide what type and dose of endocrine therapy the participant will receive.

Other Names:
  • Nolvadex
  • Apo-Tamox
  • Clonoxifen
  • Dignotamoxi
  • Ebefen
  • Emblon
  • Estroxyn
  • Fentamox
  • Genox
  • Gen-Tamoxifen
  • Jenoxifen
  • Kessar
  • Ledertam
  • Lesporene
  • Nolgen
  • Noltam
  • Nolvadex-D
  • Nourytam
  • Novofen
  • Novo-Tamoxifen
  • Oestrifen
  • Oncotam
  • PMS-Tamoxifen
  • Soltamox
  • Tamax
  • Tamaxin
  • Tamifen
  • Tamizam
  • Tamofen
  • Tamoxasta
  • Zemide
Drug: Exemestane

Exemestane is in a class of drugs called aromatase inhibitors and is considered endocrine therapy.

The treating physician will decide what type and dose of endocrine therapy the participant will receive.

Other Name: Aromasin
Drug: Goserelin

Letrozole is in a class of drugs called gonadotropin-releasing hormone (GnRH) agonists and is considered endocrine therapy. This drug is given to women who are pre-menopausal.

The treating physician will decide what type and dose of endocrine therapy the participant will receive.

Other Name: Zoladex
Active Comparator: Arm 2 - Endocrine Therapy Only
Participants will be treated with neoadjuvant endocrine therapy, with the dose and agent to be determined by the treating physician.
Drug: Anastrozole

Anastrozole is in a class of drugs called nonsteroidal aromatase inhibitors and is considered endocrine therapy.

The treating physician will decide what type and dose of endocrine therapy the participant will receive.

Other Name: Arimidex
Drug: Letrozole

Letrozole is in a class of drugs called nonsteroidal aromatase inhibitors and is considered endocrine therapy.

The treating physician will decide what type and dose of endocrine therapy the participant will receive.

Other Name: Femara
Drug: Tamoxifen

Tamoxifen is in a class of drugs called selective estrogen receptor modulators and is considered endocrine therapy.

The treating physician will decide what type and dose of endocrine therapy the participant will receive.

Other Names:
  • Nolvadex
  • Apo-Tamox
  • Clonoxifen
  • Dignotamoxi
  • Ebefen
  • Emblon
  • Estroxyn
  • Fentamox
  • Genox
  • Gen-Tamoxifen
  • Jenoxifen
  • Kessar
  • Ledertam
  • Lesporene
  • Nolgen
  • Noltam
  • Nolvadex-D
  • Nourytam
  • Novofen
  • Novo-Tamoxifen
  • Oestrifen
  • Oncotam
  • PMS-Tamoxifen
  • Soltamox
  • Tamax
  • Tamaxin
  • Tamifen
  • Tamizam
  • Tamofen
  • Tamoxasta
  • Zemide
Drug: Exemestane

Exemestane is in a class of drugs called aromatase inhibitors and is considered endocrine therapy.

The treating physician will decide what type and dose of endocrine therapy the participant will receive.

Other Name: Aromasin
Drug: Goserelin

Letrozole is in a class of drugs called gonadotropin-releasing hormone (GnRH) agonists and is considered endocrine therapy. This drug is given to women who are pre-menopausal.

The treating physician will decide what type and dose of endocrine therapy the participant will receive.

Other Name: Zoladex

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

A patient will be eligible for inclusion in this study only if ALL of the following criteria apply:

  • Newly diagnosed histologically confirmed invasive breast cancer.
  • Clinical T2-T4c, any N, M0 invasive ER+ (Allred Score of 6-8) and HER2- (0 or 1+ by IHC or FISH negative for amplification) breast cancer by AJCC 7th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node. Patients with T1c tumors are eligible if they are considered candidates for neoadjuvant endocrine therapy.
  • At least 1 measurable lesion.
  • Candidate for neoadjuvant endocrine therapy.
  • At least 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
  • Adequate organ and marrow function no more than 28 days prior to the start of neoadjuvant endocrine therapy as defined below:

    • WBC ≥3,000/μL
    • absolute neutrophil count ≥1,500/μL
    • platelets ≥100,000/μL
    • total bilirubin ≤institutional upper limit of normal
    • AST/ALT ≤2.5 X institutional upper limit of normal
    • creatinine ≤ institutional upper limit of normal OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine above IULN
  • Postmenopausal or premenopausal. NOTE: Postmenopausal women, verified by: (1) bilateral surgical oophorectomy, or (2) no spontaneous menses ≥ 1 year or (3) no menses for <1 year with FSH and estradiol levels in postmenopausal range, according to institutional standards. Premenopausal women, verified by: (1) regular menses, or (2) FSH and estradiol levels in premenopausal range, according to institutional standards.
  • Able to understand, and willing to sign a written informed consent document.
  • Confirmation that primary tumor expresses mammaglobin-A by IHC.
  • Tumor Ki67 value is ≤ 10% after 14 days of endocrine therapy.

Exclusion Criteria:

A patient will be ineligible for inclusion in this study if ANY of the following criteria apply:

  • Received any of the following for treatment of this cancer (except for the neoadjuvant endocrine therapy specified within this protocol):

    • Surgery
    • Radiation therapy
    • Chemotherapy
    • Biotherapy
    • Hormonal therapy
    • Investigational agent
  • Receiving any other investigational agent(s) or has received an investigational agent within the last 30 days.
  • Known metastatic disease.
  • Known allergy, or history of serious adverse reaction to vaccines such as anaphylaxis, hives, or respiratory difficulty.
  • Prior axillary lymph node sampling (sentinel lymph node biopsy or axillary lymph node dissection). FNA of axillary lymph node is acceptable.
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
  • Prior or currently active autoimmune disease requiring management with immunosuppression. This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication (e.g., corticosteroids) which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines. Asthma or chronic obstructive pulmonary disease that does not require daily systemic corticosteroids is acceptable. Any patients receiving steroids should be discussed with the PI to determine if eligible.
  • Pregnant or breastfeeding. A negative serum or pregnancy test is required no more than 7 days before study entry, and patients must be willing to employ adequate contraception. Women of childbearing potential must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
  • Known HIV-positive status. These patients are ineligible because of the potential inability to generate an immune response to vaccines.
  • Subjects with a strong likelihood of non-adherence such as difficulties in adhering to follow-up schedule due to geographic distance from the Siteman Cancer Center should not knowingly be registered.
  • Individuals in whom a skinfold measurement of the cutaneous and subcutaneous tissue for the eligible injection sites (left and right medial deltoid region) exceeds 40 mm
  • Individuals in whom the ability to observe possible local reactions at the eligible injection sites (deltoid region) is, in the opinion of the investigator, unacceptably obscured due to a physical condition or permanent body art
  • Therapeutic or traumatic metal implant in the skin or muscle of either deltoid region.
  • Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, or hepatic or renal functional abnormality as determined by the investigator based on medical history, physical examination, EKG, and/or laboratory screening test
  • Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child
  • Syncopal episode within 12 months of screening
  • Current use of any electronic stimulation device, such as cardiac demand pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep brain stimulators.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02204098


Contacts
Contact: William Gillanders, M.D. 314-747-0072 gillandersw@wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: William Gillanders, M.D.    314-747-0072    gillandersw@wustl.edu   
Principal Investigator: William Gillanders, M.D.         
Sub-Investigator: Foluso Ademuyiwa, M.D.         
Sub-Investigator: Rebecca Aft, M.D.         
Sub-Investigator: Amy Cyr, M.D.         
Sub-Investigator: Timothy Eberlein, M.D.         
Sub-Investigator: Timothy Fleming, Ph.D.         
Sub-Investigator: Peter Goedegebuure, Ph.D.         
Sub-Investigator: A. Craig Lockhart, M.D.         
Sub-Investigator: Julie Margenthaler, M.D.         
Sub-Investigator: Thallachallour Mohanakumar, Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: William Gillanders, M.D. Washington University School of Medicine
  More Information

Additional Information:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02204098     History of Changes
Other Study ID Numbers: 201407100
First Submitted: July 23, 2014
First Posted: July 30, 2014
Last Update Posted: July 19, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Vaccines
Letrozole
Exemestane
Anastrozole
Tamoxifen
Goserelin
Aromatase Inhibitors
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents


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