Vaccine Therapy in Treating Patients With HER2/Neu Positive or Negative Stage IV Breast Cancer or Other HER2/Neu Positive Cancers

NCT ID: NCT00095862

Last Updated: 2018-02-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-11-30

Brief Summary

RATIONALE: Vaccines made from gene-modified tumor cells may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Interferon alfa may interfere with the growth of tumor cells. Combining vaccine therapy with cyclophosphamide and interferon alfa may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining vaccine therapy with interferon alfa and cyclophosphamide in treating patients who have stage IV breast cancer.

Detailed Description

OBJECTIVES:

• Determine the safety, tolerability, and feasibility of vaccine therapy comprising an allogeneic (non-self) tumor cell line transfected with the sargramostim (GM-CSF) gene combined with low-dose interferon alfa and low-dose cyclophosphamide in patients with stage IV breast cancer or other solid tumors.
• Determine the clinical response, time to progression, and survival of patients treated with this regimen.
• Correlate clinical response with immunological response in patients treated with this regimen.

OUTLINE: Patients receive low-dose cyclophosphamide IV once 2-3 days before each tumor vaccine. Patients then receive tumor vaccine comprising HER2/neu-positive allogeneic (non-self) breast cancer cells transfected with the sargramostim (GM-CSF) gene intradermally (ID) on day 1. Patients also receive low-dose interferon alfa ID approximately 48 and 96 hours after each tumor vaccine. Treatment repeats every 2 weeks for 3 vaccinations and then monthly for 3 vaccinations in the absence of disease progression or unacceptable toxicity.

Patients are followed at 2 weeks and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 9-24 patients will be accrued for this study.

Conditions

Breast Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

allogeneic GM-CSF-secreting breast cancer vaccine

Intervention Type: BIOLOGICAL

recombinant interferon alfa

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with no HLA-A2 allele are eligible
• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female or male

Menopausal status

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• At least 4 months

Hematopoietic

• Absolute granulocyte count ≥ 1,000/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 2 mg/dL
• Alkaline phosphatase ≤ 5 times upper limit of normal (ULN)
• ALT and AST ≤ 2 times ULN

Renal

• BUN ≤ 30 mg/dL
• Creatinine ≤ 2 mg/dL
• ≤ 1 g protein on 24-hour urine collection OR
• ≤ 1+ proteinuria on urinalysis

Cardiovascular

• Hypertension controlled by agents (except beta-blockers) allowed

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No history of anaphylactic reaction to any known or unknown antigen
• No history of clinical hypersensitivity to sargramostim (GM-CSF), interferon, yeast, beef, or to any components used in preparation of study vaccine
• No clinical or laboratory features indicative of AIDS
• No rheumatological, psychiatric, or other clinically progressive major medical problems requiring treatment
• No other malignancy within the past 2 years

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 3 weeks since prior biological therapy, including trastuzumab (Herceptin^®)
• More than 3 weeks since prior immunotherapy
• No concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• More than 3 weeks since prior chemotherapy (8 weeks for nitrosoureas or mitomycin)
• No concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics
• More than 3 weeks since prior hormonal therapy
• No concurrent hormonal therapy
• No concurrent systemic steroids

• Concurrent inhalation steroids for respiratory hypersensitivity (e.g., triamcinolone nasal or pulmonary inhalers) allowed

Radiotherapy

• See Disease Characteristics
• More than 3 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• More than 3 weeks since prior major surgery with general anesthesia
• No concurrent major surgery

Other

• Recovered from prior therapy
• Patients receiving pamidronate, bisphosphonates, or other supportive measures must continue therapy during study participation
• No concurrent anticoagulants
• No concurrent beta-blockers for control of mild hypertension or other indications

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wiseman Research Initiatives LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Wiseman Research Initiatives, LLC

Principal Investigators

Charles L. Wiseman, MD, FACP

Role: STUDY_CHAIR

Locations

Glendale Memorial Hospital Comprehensive Cancer Center

Glendale, California, United States

Hollywood Presbyterian Medical Center

Los Angeles, California, United States

Los Angeles, California, United States

Countries

United States

References

Lacher MD, Bauer G, Fury B, Graeve S, Fledderman EL, Petrie TD, Coleal-Bergum DP, Hackett T, Perotti NH, Kong YY, Kwok WW, Wagner JP, Wiseman CL, Williams WV. SV-BR-1-GM, a Clinically Effective GM-CSF-Secreting Breast Cancer Cell Line, Expresses an Immune Signature and Directly Activates CD4+ T Lymphocytes. Front Immunol. 2018 May 15;9:776. doi: 10.3389/fimmu.2018.00776. eCollection 2018.

Reference Type: DERIVED

PMID: 29867922 (View on PubMed)

Other Identifiers

WRI-GEV-007

Identifier Type: -

Identifier Source: secondary_id

CDR0000393552

Identifier Type: -

Identifier Source: org_study_id