Ad/HER2/Neu Dendritic Cell Cancer Vaccine Testing

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01730118
First received: November 17, 2012
Last updated: July 12, 2014
Last verified: April 2014
  Purpose

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 four doses of the vaccine at study Weeks 0, 4, 8, and 24.
  • Participants will be monitored with physical exams, frequent blood tests and imaging studies....

Condition Intervention Phase
Breast Neoplasms
Breast Cancer
Adenocarcinomas
Metastatic Solid Tumors Characterized by HER2/Neu Expression
Biological: Autologous Ad HER2 dendritic cell vaccine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Fraction of subjecs with cardiac toxicity [ Time Frame: Through 2 years after receipt of last dose ]
  • Increase in anit-HER2/neu antibody concentration or increase in antibody dilution titers [ Time Frame: Through 2 years after receipt of last dose ]

Secondary Outcome Measures:
  • ORR by immune related response criteria [ Time Frame: 1 year (weeks 12, 16, 28, 32, 48 and 52 after initial vaccination) ]

Estimated Enrollment: 65
Study Start Date: November 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
HER2+ metasatic solid tumors and bladder cancer
Biological: Autologous Ad HER2 dendritic cell vaccine
N/A
Experimental: 2
HER2+ breast cancer
Biological: Autologous Ad HER2 dendritic cell vaccine
N/A

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION PART I
  • Adults greater than or equal to 18 with recurrent or progressive, metastatic solid tumors characterized by some HER2/neu expression that have failed standard therapies with known benefit but for whom trastuzumab is not clinically indicated:
  • Patients with ovarian, colon, non-small cell lung, renal cell, bladder and prostate cancer that are known to be HER2 1+, 2+ or 3+ by IHC OR have a Vysis FISH result greater than 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.

2.1.1.3 Life expectancy of greater than or equal to 6 months,

  • Performance Status: ECOG 0-1.
  • Naive to trastuzumab, pertuzumab and lapatnib or other investigational HER2-directed therapies (e.g. T-DM1).
  • Recurrent or progressive disease on prior standard therapies with known clinical benefit (except adjuvant bladder cancer population).
  • For adults with recurrent, metastatic solid tumors: presence of measurable disease, defined as at least one lesion that can be accurately measured by CT scan in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques and/or measurable, clinically visible skin lesions, with the exception of metastatic bladder cancer patients that have completed first line chemotherapy and may not have measurable disease.
  • Baseline LVEF by 2D Echocardiogram greater than or equal to 55%.
  • Greater than or equal to 2 weeks since standard or investigational treatment for metastatic disease.
  • Stable, concurrent use of tamoxifen or aromatase inhibitors for ER+ status allowed.
  • Hematologic parameters: ANC greater than or equal to 1000 cells/mm(3), ALC greater than or equal to 500 cells/mm(3), Hemoglobin greater than or equal to 9.0 gm/dL, WBC greater than or equal to 2,500 cells/mm(3), platelet count greater than or equal to 75,000/mm3, PT/PTT less than or equal to 1.5 times the upper limits of normal.
  • Chemistry paramters: SGOT and SGPT less than or equal to 3 times the upper limits of normal and total bilirubin less than or equal to 1.5 mg/dl, Alk PO4 less than or equal to 3 times the upper limits of normal (except for patients with documented metastatic diseease to bone and or liver).
  • Negative serum HCG if female and of childbearing potential.
  • Negative serology for HIV-1.
  • 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 PART II:

  • Age greater than or equal to 18 years
  • Breast cancer patients with 3+ HER2/neu expression by IHC or a Vysis FISH result greater than 2.2.
  • Recurrent or progressive metastatic disease after at least 1-2 courses of standard therapies with known clinical benefit i.e. trastuzumab or lapatinib, ado-trastuzumab emtansine (TDM1) or other investigational HER2-directed therapies (e.g. MGAH22).
  • Life expectancy of greater than or equal to 6 months.
  • Performance Status: ECOG 0-1.
  • Presence of measurable disease, defined as at least one lesion that can be accurately measured by CT scan in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques and/or measurable clinical visible skin lesions.
  • Baseline LVEF by 2D Echocardiogram greater than or equal to 55%.
  • Greater than or equal to 2 weeks since receipt of standard or investigational HER2- directed therapy for metastatic or recurrent disease.
  • Stable, concurrent use of tamoxifen or aromatase inhibitors for ER+ status allowed.
  • Hematologic parameters: ANC greater than or equal to 1000 cells/mm(3), ALC greater than or equal to 500 cells/mm(3), absolute Hemoglobin greater than or equal to 9.0 gm/dL, WBC greater than or equal to 2,500 cells/mm(3), platelet count greater than or equal to 75,000/mm(3), PT/PTT less than or equal to 1.5 times the upper limits of normal.
  • Chemistry parameters: SGOT and SGPT less than or equal to 3 times ULN, total bilirubin less than or equal to 1.5 times ULN and Alk PO4 less than or equal to 3 times ULN (except for patients with documented metastatic disease to bone and or liver).
  • Negative serum HCG if of childbearing potential.
  • Negative serology for HIV-1.
  • 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:

  • Females who are pregnant or breastfeeding.
  • Patients with active or previously treated CNS metastases or leptomeningeal involvement by tumor.
  • 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 greater than or equal to NYHA Class II symptoms, angina, myocardial infarction or cardiac arrhythmias requiring treatment or discontinuation of chemotherapy.
  • History of changes in baseline LVEF that occurred during prior treatment with trastuzumab.
  • Cumulative doxorubicin dose greater than or equal to 400mg/m(2) or cumulative epirubicin dose greater than or equal to 800mg/m(2).
  • Use of any standard chemotherapy or other investigational agent(s) within 2 weeks 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01730118

Contacts
Contact: Brenda D Roberson, R.N. (301) 435-4733 broberson@mail.nih.gov
Contact: Lauren V Wood, M.D. (301) 402-0199 woodl@mail.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
Investigators
Principal Investigator: Lauren V Wood, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01730118     History of Changes
Other Study ID Numbers: 130016, 13-C-0016
Study First Received: November 17, 2012
Last Updated: July 12, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
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
Breast Diseases
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Skin Diseases

ClinicalTrials.gov processed this record on October 29, 2014