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Ad/HER2/Neu Dendritic Cell Cancer Vaccine Testing

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01730118
Recruitment Status : Completed
First Posted : November 21, 2012
Results First Posted : September 10, 2022
Last Update Posted : September 10, 2022
Sponsor:
Information provided by (Responsible Party):
Hoyoung M. Maeng, M.D., National Cancer Institute (NCI)

Brief Summary:

Background:

- Human epidermal growth factor receptor 2 (HER2, also known as c-erbB2 or neu)/neu (HER2) is a tumor protein that appears in almost a third of breast cancers and in several other types of cancers such as colon, prostate and non-small cell lung. Tumors that overexpress HER2 can be associated with a more aggressive cancer, higher recurrence rates, and reduced survival rates. Researchers are testing a therapeutic cancer vaccine designed to stimulate the immune system to recognize HER2. The vaccine, called adenoviral transduced autologous human epidermal growth factor receptor (AdHER)/neu dendritic cell vaccine, is custom-made using an individual's own immune cells. These cells will be collected and used to produce the vaccine.

Objectives:

- To test the safety and effectiveness of AdHER2 vaccination.

Eligibility:

- Individuals at least 18 years of age who have HER2-expressing tumors.

Design:

  • Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies will also be performed.
  • Participants will have an apheresis procedure to collect immune cells to create the vaccine.
  • Participants will receive five doses of the vaccine at study Weeks 0, 4, 8, 16 and 24.
  • Participants will be monitored with physical exams, frequent blood tests and imaging studies.

Condition or disease Intervention/treatment Phase
Breast Neoplasms Breast Cancer Adenocarcinomas Metastatic Solid Tumors Characterized by HER2/Neu Expression Biological: Adenoviral Transduced Autologous Human Epidermal Growth Factor Receptor (AdHER)2/neu Dendritic Cell (DC) Vaccine Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of an Adenoviral Transduced Autologous Dendritic Cell Vaccine Expressing Human HER2/Neu ECTM in Adults With Tumors With 1-3+ HER2/Neu Expression
Actual Study Start Date : March 4, 2013
Actual Primary Completion Date : December 3, 2019
Actual Study Completion Date : December 3, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaccines

Arm Intervention/treatment
Experimental: 1/Part I dose escalation
Adenoviral Transduced Autologous Human epidermal growth factor receptor (AdHER) dendritic cell (DC) vaccine administered at escalating doses
Biological: Adenoviral Transduced Autologous Human Epidermal Growth Factor Receptor (AdHER)2/neu Dendritic Cell (DC) Vaccine
autologous AdHER2 transduced dendritic cell vaccine manufactured under Good Manufacturing Practices (GMP) conditions from cryopreserved patient monocytes here at the National Institutes of Health (NIH) Clinical Center (CC) Department of Transfusion Medicine (DTM). Vaccine is administered intradermally at assigned dose level at weeks 0, 4, 8, 16 and 24 of the study.

Experimental: 2/Part I dose expansion
Adenoviral Transduced Autologous Human epidermal growth factor receptor (AdHER) dendritic cell (DC) vaccine administered at a next lower dose or the highest dose
Biological: Adenoviral Transduced Autologous Human Epidermal Growth Factor Receptor (AdHER)2/neu Dendritic Cell (DC) Vaccine
autologous AdHER2 transduced dendritic cell vaccine manufactured under Good Manufacturing Practices (GMP) conditions from cryopreserved patient monocytes here at the National Institutes of Health (NIH) Clinical Center (CC) Department of Transfusion Medicine (DTM). Vaccine is administered intradermally at assigned dose level at weeks 0, 4, 8, 16 and 24 of the study.

Experimental: 3/Part 1 dose escalation
Adenoviral Transduced Autologous Human epidermal growth factor receptor (AdHER) dendritic cell (DC) vaccine administered at Dose Level 1
Biological: Adenoviral Transduced Autologous Human Epidermal Growth Factor Receptor (AdHER)2/neu Dendritic Cell (DC) Vaccine
autologous AdHER2 transduced dendritic cell vaccine manufactured under Good Manufacturing Practices (GMP) conditions from cryopreserved patient monocytes here at the National Institutes of Health (NIH) Clinical Center (CC) Department of Transfusion Medicine (DTM). Vaccine is administered intradermally at assigned dose level at weeks 0, 4, 8, 16 and 24 of the study.

Experimental: 4/Part II dose escalation
Adenoviral Transduced Autologous Human epidermal growth factor receptor (AdHER) dendritic cell (DC) vaccine administered at Dose Level 1
Biological: Adenoviral Transduced Autologous Human Epidermal Growth Factor Receptor (AdHER)2/neu Dendritic Cell (DC) Vaccine
autologous AdHER2 transduced dendritic cell vaccine manufactured under Good Manufacturing Practices (GMP) conditions from cryopreserved patient monocytes here at the National Institutes of Health (NIH) Clinical Center (CC) Department of Transfusion Medicine (DTM). Vaccine is administered intradermally at assigned dose level at weeks 0, 4, 8, 16 and 24 of the study.

Experimental: 5/Part II dose expansion
Adenoviral Transduced Autologous Human epidermal growth factor receptor (AdHER) dendritic cell (DC) vaccine administered at Arm 1 maximum tolerated dose (MTD)
Biological: Adenoviral Transduced Autologous Human Epidermal Growth Factor Receptor (AdHER)2/neu Dendritic Cell (DC) Vaccine
autologous AdHER2 transduced dendritic cell vaccine manufactured under Good Manufacturing Practices (GMP) conditions from cryopreserved patient monocytes here at the National Institutes of Health (NIH) Clinical Center (CC) Department of Transfusion Medicine (DTM). Vaccine is administered intradermally at assigned dose level at weeks 0, 4, 8, 16 and 24 of the study.




Primary Outcome Measures :
  1. Number of Participants With Cardiac Toxicity [ Time Frame: Baseline through receipt of last dose of vaccine, up to 24 weeks ]
    Cardiac toxicity defined as cardiac dysfunction due to damage to the heart muscles or valves. Cardiac toxicity was assessed by serial echocardiography to determine left ventricular ejection fraction (LVEF) at baseline and following receipt of the last dose of vaccine. Cardiac toxicity is at least a 10% decline from the baseline in cardiac function. Normal LVEF is >-53%. Below 53% is a cardiac dysfunction.

  2. Number of Participants Who Develop at Least a 4-fold or 2.5- Fold Increase in Anti-Human Epidermal Growth Factor Receptor (HER2)/Neu Antibody Dilution Titers [ Time Frame: Baseline through last dose of vaccine, up to 24 weeks ]
    Vaccine immunogenicity was determined by the number of participants who develop at least a 4-fold increase in antibody dilution titers over baseline at the time points measured. The antibody response following the vaccination was assessed using peptide-array and reported as fold increase compared to the baseline values using the cut-off of 4 fold per study definition of the vaccine immunogenicity and also of 2.5 fold to aid the interpretation of the result.


Secondary Outcome Measures :
  1. Number of Participants Who Experienced Tumor Shrinkage or Stabilization That is Sufficient by Modified Immune Response Related Criteria (irRC) to be Considered Stable Disease (SD), a Partial Response (PR) or Better (Complete Response (CR) [ Time Frame: At 8, 16, 24, 36, 48, 76, 100, and 124 weeks after initial vaccination ]
    Number of participants who experienced tumor shrinkage or stabilization that is sufficient by modified immune response related criteria (irRC) to be considered stable disease (SD), a partial response (PR) or better (complete response (CR). SD is neither partial response nor progressive disease (PD). PR is ≥ 30% decrease in tumor burden compared with baseline, confirmation required. CR is disappearance of all target and non-target lesions. Lymph nodes must regress to <10mm short axis. No new lesions, confirmation required. PD ≥ 20% increase in tumor burden compared with baseline, with nadir, or reset baseline. New lesions added to the tumor burden, confirmation required.


Other Outcome Measures:
  1. Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) [ Time Frame: Date treatment consent signed to date off study, approximately 29 months and 13 days, 28 months and 28 days, 40 months and 2 days, 24 months and 23 days, 25 months and 30 days, and 28 months and 3 days for each group respectively. ]
    Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.



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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • ELIGIBILITY CRITERIA:

Common Eligibility for Parts I and II

  • Adults greater than or equal to 18 with malignant soft tissue and bone tumors and recurrent or progressive, metastatic solid tumors who have progressed on standard therapies except in adjuvant for high risk bladder cancer in Part I.
  • Recurrent or progressive disease on prior standard therapies with known clinical benefit with the exception of adjuvant bladder cancer population.
  • Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-1.
  • Baseline left ventricular ejection fraction (LVEF) by two-dimensional (2D) Echocardiogram greater than or equal to 53%.
  • Greater than or equal to 1 week since standard or investigational treatment for metastatic disease.
  • Stable, concurrent use of hormone therapy for hormone receptor positive breast cancer is permitted.
  • Hematologic parameters: absolute neutrophil count (ANC) greater than or equal to 1000 cells/mm^3, absolute lymphocyte count (ALC) greater than or equal to 300 cells/mm^3, Hemoglobin greater than or equal to 9.0 gm/dL, white blood cell (WBC) greater than or equal to 2,500 cells/mm^3, platelet count greater than or equal to 75,000/mm^3, prothrombin time (PT)/partial thromboplastin time (PTT) less than or equal to 1.5X the upper limits of normal.
  • Chemistry parameters: Creatinine less than or equal to 1.5 mg/dL, serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) less than or equal to 3X the upper limits of normal and total bilirubin less than or equal to 1.5 mg/dl, Alkaline phosphatase (Alk PO4) less than or equal to 3X the upper limits of normal (except for patients with documented metastatic disease to bone and/or liver).
  • Negative serum beta human chorionic gonadotropin (HCG) if female and of childbearing potential.
  • Negative human immunodeficiency virus (HIV) 1/2 serology and sample drawn for human T-cell lymphotropic virus (HTLV). Patients with HIV are excluded from participating on this clinical trial because their immunodeficiency would confound the evaluation of adverse events which would hinder meeting the primary objective.
  • Negative serology for hepatitis B and C unless the result is consistent with prior vaccination or prior infection with full recovery.
  • Willingness of female and male subjects to use effective contraception e.g., oral contraceptives, barrier device, intrauterine device, or condoms, during the study and for three months following the last dose of study vaccine. We suggest that subjects do not become pregnant or father a child during the study, and for 3 months following receipt of the investigational adenoviral transduced autologous human epidermal growth factor receptor (AdHER) dendritic cell (DC) vaccine.
  • Able to understand and provide Informed Consent.
  • Patients with 1+ to 3+ human epidermal growth factor receptor 2 (HER2)/neu expression by immunohistochemistry (IHC) or an equivocal or positive fluorescence in situ hybridization (FISH) result by 2013 American Society of Clinical Oncology (ASCO)/Corrective Action Plan (CAP) guideline.
  • Patients must have measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Part I Eligibility

  • Naive to trastuzumab (Herceptin), pertuzumab (Perjeta) and lapatinib (Tykerb), ado-trastuzumab emtansine (Kadcyla) or other HER2-directed therapies.
  • Malignancy as follows:
  • Malignant soft tissue and bone tumors and recurrent or progressive, metastatic solid tumors who have progressed on standard therapies; or,
  • Bladder cancer in the adjuvant setting (adjuvant bladder cancer patients):

    • Tumor stage T3a, T3b, T4a, T4b and any node positive disease regardless of tumor stage.
    • Status-post primary cystectomy with curative intent.
    • May or may not have received neoadjuvant cisplatin-based combination chemotherapy per National Comprehensive Cancer Network (NCCN) guidelines.
    • May or may not have received adjuvant radiotherapy or chemotherapy based on pathologic risk per NCCN guidelines.
    • Greater than or equal to 6 weeks s/p primary surgery with curative intent.
  • NOTE: Patients with breast, ovarian, cervical, colon, gastric/gastroesophageal junction, non-small cell lung, renal cell, bladder, malignant soft tissue and bone tumor, prostate cancer or other solid tumors.

Part II Eligibility

  • Malignant soft tissue and bone tumors and recurrent or progressive, metastatic solid tumors who have progressed on standard therapies.
  • Recurrent or progressive metastatic disease after standard of care HER2-targeted therapies, i.e., trastuzumab (Herceptin), pertuzumab (Perjeta), lapatinib (Tykerb), ado-trastuzumab emtansine (TDM1) (Kadcyla) or other HER2-directed therapies.
  • Stable, concurrent use of tamoxifen or aromatase inhibitors for hormone receptor positive breast cancer is permitted.

EXCLUSION CRITERIA:

  • Pregnant women are excluded from this study because Adenoviral Transduced Autologous Human epidermal growth factor receptor (AdHER) dendritic cell (DC) vaccine may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AdHER DC vaccine, breastfeeding should be discontinued if the mother is treated with AdHER DC vaccine.
  • Patients with active central nervous system (CNS) metastases or leptomeningeal involvement by tumor (patients with a history of brain metastases who have successfully treated for brain metastasis by surgery or radiation and who have not had any evidence of the new or progressive CNS disease for more than 12 months are eligible).
  • Patients with rapidly progressing disease in the opinion of the Principal Investigator.
  • Patients with inadequate bilateral peripheral venous or central venous catheter access for the required apheresis to allow generation of the autologous AdHER2 DC vaccine product.
  • Clinically significant cardiac dysfunction defined as a history of > New York Heart Association (NYHA) Class II symptoms, angina, congestive heart failure, myocardial infarction, arrhythmias or cardiac dysfunction requiring treatment or discontinuation of chemotherapy.
  • History of changes in baseline LVEF that occurred during prior treatment with anti-HER2 treatment.
  • Cumulative doxorubicin dose > 400mg/m^2 (>450 mg/m^2 for malignant soft tissue and bone tumor patients) or cumulative epirubicin dose > 800mg/m^2.
  • Use of any standard chemotherapy or other investigational agent(s) within 1 week of study enrollment.
  • Use of systemic corticosteroid therapy within 2 weeks of study enrollment, including patients receiving replacement corticosteroid therapy. Note: only topical, inhaled and intranasal steroid therapy is permitted.
  • Active systemic viral, bacterial or fungal infection requiring treatment.
  • A medical history which the treating physician believes causes the patient to be excluded. This includes a remote history of cancer. Please note: Squamous cell carcinoma, basal cell carcinoma and remote history of cancer with no evidence of recurrence for the past 5 years are eligible.

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): NCT01730118


Locations
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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Hoyoung M Maeng, M.D. National Cancer Institute (NCI)
  Study Documents (Full-Text)

Documents provided by Hoyoung M. Maeng, M.D., National Cancer Institute (NCI):
Informed Consent Form: Standard Consent  [PDF] August 19, 2019

Additional Information:
Publications:
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Responsible Party: Hoyoung M. Maeng, M.D., Principal Investigator, National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01730118    
Other Study ID Numbers: 130016
13-C-0016
First Posted: November 21, 2012    Key Record Dates
Results First Posted: September 10, 2022
Last Update Posted: September 10, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. All collected IPD will be shared with collaborators under the terms of collaborative agreements.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Clinical data available during the study and indefinitely.
Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hoyoung M. Maeng, M.D., National Cancer Institute (NCI):
Metastatic Solid Tumors
Human Epidermal Growth Factor Receptor 2 Expression (HER2/neu)
Trastuzumab Exposure
Dendritic Cell Vaccine
Breast Cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action