Description:
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.
Title
- Brief Title: Vaccine Therapy in Treating Patients With HER2/Neu Positive or Negative Stage IV Breast Cancer or Other HER2/Neu Positive Cancers
- 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
Clinical Trial IDs
- ORG STUDY ID:
CDR0000393552
- SECONDARY ID:
WRI-GEV-007
- NCT ID:
NCT00095862
Conditions
- Breast Cancer
- Unspecified Adult Solid Tumor, Protocol Specific
Interventions
| Drug | Synonyms | Arms |
|---|
| allogeneic GM-CSF-secreting breast cancer vaccine | | |
| recombinant interferon alfa | | |
| cyclophosphamide | | |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
Eligibility Criteria
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
| Maximum Eligible Age: | 120 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Safety, tolerability, and feasibility |
| Time Frame: | |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Terminated |
| Lead Sponsor: | Wiseman Research Initiatives LLC |
Trial Keywords
- recurrent breast cancer
- stage IV breast cancer
- male breast cancer
- unspecified adult solid tumor, protocol specific
Last Updated
February 5, 2018
