Phase 1 N=27 Treatment

Ad/HER2/Neu Dendritic Cell Cancer Vaccine Testing

Breast Neoplasms · Breast Cancer · Adenocarcinomas · Metastatic Solid Tumors Characterized by HER2/Neu Expression

Bottom Line

View on ClinicalTrials.gov: NCT01730118 ↗

Enrolled (actual)

Serious AEs

69.7%

Results posted

Sep 2022

Primary outcome: Primary: Number of Participants With Cardiac Toxicity — 6; 7; 6; 6 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: Adenoviral Transduced Autologous Human Epidermal Growth Factor Receptor (AdHER)2/neu Dendritic Cell (DC) Vaccine (Biological)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Cancer Institute (NCI)
Primary completion: Dec 2019

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Cardiac Toxicity	6; 7; 6; 6; 3; 3	—
PRIMARY 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	0; 0; 1; 0; 0; 0	—
SECONDARY 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)	0; 2; 1; 1; 0; 1	—

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.

Eligibility 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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01730118). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.