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Ad/HER2/Neu Dendritic Cell Cancer Vaccine Testing

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ClinicalTrials.gov Identifier: NCT01730118
Recruitment Status : Recruiting
First Posted : November 21, 2012
Last Update Posted : November 1, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

- HER2/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 AdHER2/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: AdHER2/neu DC Vaccine Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Allocation: Non-Randomized
Intervention Model: Parallel 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
Study Start Date : November 17, 2012
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 1/Part I dose escalation
AdHER DC vaccine administered at escalating doses
Biological: AdHER2/neu DC Vaccine
Autologous AdHER2 transduced dendritic cell vaccine manufactured under GMP conditions from cryopreserved patient monocytes here at the NIH CC 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
AdHER DC vaccine administered at a next lower dose or the highest dose
Biological: AdHER2/neu DC Vaccine
Autologous AdHER2 transduced dendritic cell vaccine manufactured under GMP conditions from cryopreserved patient monocytes here at the NIH CC DTM. Vaccine is administered intradermally at assigned dose level at weeks 0, 4, 8, 16 and 24 of the study.

Experimental: 3/Part II dose escalation
AdHER DC vaccine administered at Dose Level 1
Biological: AdHER2/neu DC Vaccine
Autologous AdHER2 transduced dendritic cell vaccine manufactured under GMP conditions from cryopreserved patient monocytes here at the NIH CC 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 expansion
AdHER DC vaccine administered at Arm 1 MTD
Biological: AdHER2/neu DC Vaccine
Autologous AdHER2 transduced dendritic cell vaccine manufactured under GMP conditions from cryopreserved patient monocytes here at the NIH CC DTM. Vaccine is administered intradermally at assigned dose level at weeks 0, 4, 8, 16 and 24 of the study.




Primary Outcome Measures :
  1. Fraction of subjects with cardiac toxicity [ Time Frame: Through 2 years after receipt of last dose ]
    Determine an approximate estimate of the vaccine immunogenicity.

  2. Increase in anti-HER2/neu antibody concentration or increase in antibody dilution titers [ Time Frame: Through 2 years after receipt of last dose ]
    Determine an approximate estimate of the vaccine immunogenicity.


Secondary Outcome Measures :
  1. ORR by immune related response criteria [ Time Frame: 1 year (weeks 12, 16, 28, 32, 48 and 52 after initial vaccination) ]
    obtain a preliminary estimate of the proportion of patients who may experience tumor shrinkage or stabilization that is sufficient by modified immune response related criteria (irRC) to be considered stable disease, a partial response or better.



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA for PART I
  • 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 with known benefit but for whom anti-HER2 therapy is not clinically indicated:

    • Patients with 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 that is known to be HER2 1+, 2+ or 3+ by IHC OR have a Vysis FISH result greater than or equal to 1.8.
    • Patients with breast cancer that is known to be HER2 1+ or 2+ by IHC or with a Vysis FISH result of 1.8 - less than 2.2.
  • Adults greater than or equal to 18 with HER2+ 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.
    • Tumors that are HER2 1+, 2+ or 3+ by IHC or have a Vysis FISH result greater than 1.8.
    • Status-post primary cystectomy with curative intent.
    • May or may not have received neoadjuvant cisplatin-based combination chemotherapy per 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.
  • Performance Status: ECOG 0-1.
  • Naive to trastuzumab (Herceptin(TM)), pertuzumab (Perjeta(TM)) and lapatinib (Tykerb(TM)), ado-trastuzumab emtansine (Kadcyla(TM)) or other HER2-directed therapies.
  • Recurrent or progressive disease on prior standard therapies with known clinical benefit with the exception of adjuvant bladder cancer population.
  • Patients must have measurable disease, per RECIST 1.1 for the evaluation of measurable disease.
  • Baseline LVEF by 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 tamoxifen or aromatase inhibitors for hormone receptor positive breast cancer.
  • Hematologic parameters: ANC >= 1000 cells/mm^3, ALC >= 300 cells/mm^3, Hemoglobin >= 9.0 gm/dL, WBC >= 2,500 cells/mm^3, platelet count >= 75,000/mm^3, PT/PTT less than or equla to1.5X the upper limits of normal.
  • Chemistry parameters: Creatinine less than 1.5 mg/dL, SGOT and SGPT less than or equal to 3X the upper limits of normal and total bilirubin less than or equal to 1.5 mg/dl, 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 HCG if female and of childbearing potential.
  • Negative serology for anti-HIV-1/2 and anti-HTLV 1/2.
  • 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 AdHER2 DC vaccine. (FDA requested language)
  • Able to understand and provide Informed Consent.

INCLUSION CRITERIA for PART II:

  • Age greater than or equal to 18 years
  • Patients with breast cancer, gastric, gastroesophageal junction or other cancers with 1+ to 3+ HER2/neu expression by IHC or a Vysis FISH result > 2.2.
  • Recurrent or progressive metastatic disease after standard of care HER2-targeted therapies i.e. trastuzumab (Herceptin(TM)), pertuzumab (Perjeta(TM)), lapatinib (Tykerb(TM)), ado-trastuzumab emtansine (TDM1) (Kadcyla(TM)) or other HER2-directed therapies.
  • Perormance Status: ECOG 0-1.
  • Patients must have measurable disease, per RECIST 1.1.
  • Baseline LVEF by 2D Echocardiogram greater than or equal to 53%.
  • Greater than or equal to 1 week since receipt of standard or investigational HER2- directed therapy for metastatic or recurrent disease.
  • Stable, concurrent use of tamoxifen or aromatase inhibitors for hormone receptor positive breast cancer are allowed.
  • Hematologic parameters: ANC >= 1000 cells/mm^3, ALC >= 300 cells/mm^3, absolute Hemoglobin >=9.0 gm/dL, WBC >=2500 cells/mm3, platelet count >=75,000/mm^3, PT/PTT 1.5X the upper limits of normal.
  • Chemistry parameters: Creatinine less than mg/dL, SGOT and SGPT less than or equal to 3X ULN, total bilirubin less than or equal to 1.5X ULN and Alk PO4 less than or equal to 3X ULN (except for patients with documented metastatic disease to bone and/or liver).
  • Negative serum beta HCG if of childbearing potential.
  • Negative serology for anti-HIV-1/2 and anti-HTLV 1/2.
  • Negative serology for hepatitis B and C unless the result is consistent with prior vaccination or prior infection with full recovery.
  • Willingness of female 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 during the study, and for 3 months following receipt of the investigational AdHER2 DC vaccine. (FDA requested language)
  • Able to understand and provide Informed Consent.

EXCLUSION CRITERIA:

-Pregnant women are excluded from this study because AdHER 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 CNS metastases or leptomeningeal involvement by tumor (patients with a history of brain metastases who have been successfully treated for brain metastasis by surgery or radiation and who have not had any evidence of the new or progressive CNS disease fot 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 >= 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.

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


Contacts
Contact: Lee C England, P.A.-C (240) 858-3649 lee.england@nih.gov
Contact: Hoyoung M Maeng, M.D. (240) 781-3253 hoyoung.maeng@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Hoyoung M Maeng, M.D. National Cancer Institute (NCI)

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01730118     History of Changes
Other Study ID Numbers: 130016
13-C-0016
First Posted: November 21, 2012    Key Record Dates
Last Update Posted: November 1, 2018
Last Verified: October 18, 2018

Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by National Institutes of Health Clinical Center (CC) ( 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:
Adenocarcinoma
Breast Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs