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

Sponsor

Wiseman Research Initiatives LLC (Industry)

Overall Status

Terminated

CT.gov ID

NCT00095862

Collaborator

(none)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Unspecified Adult Solid Tumor, Protocol Specific	Biological: allogeneic GM-CSF-secreting breast cancer vaccine Biological: recombinant interferon alfa Drug: cyclophosphamide	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1-2 Study for Stage IV Breast and HER2/Neu Positive Cancers to Evaluate the Safety and Efficacy of a Vaccine Using Whole Cells From the SVBR- 1-GM Cell Line Genetically Engineered To Produce Granulocyte- Macrophage Colony Stimulating Factor

Study Start Date :

Nov 1, 2004

Outcome Measures

Primary Outcome Measures

Safety, tolerability, and feasibility []
Clinical response []
Time to progression []
Survival []
Correlation of clinical response with immunological response []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed breast cancer meeting 1 of the following criteria:
Recurrent and/or metastatic lesions that are HER2/neu-positive or negative
Recurrent or progressive cancer of the lung, ovary, pancreas, prostate, bladder, or other primary site associated with HER2/neu-positive tumor by histochemistry
Bone-only metastatic breast cancer, cytologically confirmed malignant effusions, histologically confirmed marrow involvement, or other evaluable (but non-measurable) metastatic disease allowed
Failed prior first-line chemotherapy (e.g., anthracycline- or taxane-based therapy) with or without adjuvant chemotherapy or hormonal therapy
No curative or reliably effective palliative surgery, radiotherapy, or medical therapy available
Stable brain metastases allowed provided the following criteria are met*:
Previously treated
No concurrent requirement for corticosteroids
No radiological or clinical deterioration within the past 6 weeks NOTE: *Patients who had recent treatment with gamma knife or intensity-modulated radiotherapy for brain metastases are eligible provided there has been recovery from known or anticipated toxic effects
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Glendale Memorial Hospital Comprehensive Cancer Center	Glendale	California	United States	91204
2	Hollywood Presbyterian Medical Center	Los Angeles	California	United States	90027-0902
3		Los Angeles	California	United States	90057