Description:
RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an effective
immune response to kill tumor cells. Biological therapies, such as cyclophosphamide and
trastuzumab, may increase the number of immune cells and make the immune response stronger.
It is not yet known whether giving cyclophosphamide together with vaccine therapy is more
effective with or without trastuzumab in treating patients with metastatic breast cancer.
PURPOSE: This randomized phase II trial is studying the side effects of giving
cyclophosphamide together with vaccine therapy and to see how well it works compared with
giving cyclophosphamide and vaccine therapy together with trastuzumab in treating patients
with metastatic breast cancer.
Title
- Brief Title: Cyclophosphamide and Vaccine Therapy With or Without Trastuzumab in Treating Patients With Metastatic Breast Cancer
- Official Title: A Randomized, Open-Label Comparative Study of Combination Therapy With Cyclophosphamide and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine With or Without Trastuzumab for the Treatment of Metastatic Breast Cancer That Does NOT Over-express HER-2/Neu
Clinical Trial IDs
- ORG STUDY ID:
J0947
- SECONDARY ID:
P30CA006973
- SECONDARY ID:
JHOC-J0947
- SECONDARY ID:
NA_00024527
- SECONDARY ID:
GENENTECH-JHOC-J0947
- SECONDARY ID:
CDR0000653173
- NCT ID:
NCT00971737
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| allogeneic GM-CSF-secreting breast cancer vaccine | | Cyclophosphamide and Vaccine only |
| trastuzumab | | Cyclophosphamide, Vaccine and Trastuzumab |
| cyclophosphamide | | Cyclophosphamide and Vaccine only |
Purpose
RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an effective
immune response to kill tumor cells. Biological therapies, such as cyclophosphamide and
trastuzumab, may increase the number of immune cells and make the immune response stronger.
It is not yet known whether giving cyclophosphamide together with vaccine therapy is more
effective with or without trastuzumab in treating patients with metastatic breast cancer.
PURPOSE: This randomized phase II trial is studying the side effects of giving
cyclophosphamide together with vaccine therapy and to see how well it works compared with
giving cyclophosphamide and vaccine therapy together with trastuzumab in treating patients
with metastatic breast cancer.
Detailed Description
OBJECTIVES:
Primary
- To evaluate the safety of cyclophosphamide-modulated vaccination with vs without
trastuzumab in patients with breast cancer that does not overexpress HER-2/neu.
- To compare the clinical benefit of cyclophosphamide-modulated vaccination with vs
without trastuzumab in these patients.
- To measure HER-2/neu-specific CD4+ and CD8+ T-cell immunity by delayed-type
hypersensitivity (DTH) and ELISPOT.
- To measure the pharmacodynamics of CD4+CD25+ regulatory T cells by flow cytometry.
Secondary
- To assess the impact of trastuzumab on immune priming in vivo by immunohistochemistry of
vaccine-site biopsies at day +3 and day +7 of courses 1 and 3 on the two study arms,
comparing cellular infiltrates to those seen in previous preclinical and clinical
models.
- To measure hTERT-specific CD8+ T-cell immunity by ELISPOT.
- To characterize the peripheral-memory T-cell pool.
Tertiary
- To determine baseline and change in vaccine site-draining lymph node immunohistology and
gene expression profile.
- To develop the tandem tetramer/CD107a cytotoxicity assay for HER-2/neu-specific CD8+ T
cells.
- To measure novel T-cell responses induced by trastuzumab and cyclophosphamide-modulated
vaccination.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic
GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6
weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Patients then receive a fourth vaccination at 6-8 months.
- Arm II: Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV
over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the
absence of disease progression or unacceptable toxicity. Patients then receive a fourth
vaccination at 6-8 months.
Skin punch and lymph node biopsies are collected at baseline and on days +3 and +7 of courses
1 and 3 for biomarker analysis.
After completion of study treatment, patients are followed periodically.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Cyclophosphamide and Vaccine only | Active Comparator | Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. | - allogeneic GM-CSF-secreting breast cancer vaccine
- cyclophosphamide
|
| Cyclophosphamide, Vaccine and Trastuzumab | Experimental | Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. | - allogeneic GM-CSF-secreting breast cancer vaccine
- trastuzumab
- cyclophosphamide
|
Eligibility Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma of the breast
- Does not overexpress HER-2/neu, defined as FISH negative or 0, 1+, or 2+ by IHC
- Stage IV disease
- Must not be eligible for therapy of known curative potential for metastatic breast
cancer
- Measurable or evaluable disease
- Stable CNS disease allowed provided that it's adequately treated and not under active
treatment
- Hormone receptor status not specified
PATIENT CHARACTERISTICS:
- Menopausal status not specified
- ECOG performance status 0-1
- ANC > 1,000/mm^3
- Platelets > 100,000/mm^3
- Serum bilirubin < 2.0 mg/dL (unless due to Gilbert syndrome)
- AST and ALT < 2 times upper limit of normal (ULN)
- Alkaline phosphatase < 5 times ULN
- Serum creatinine < 2.0 mg/dL
- Ejection fraction normal by MUGA OR ≥ 50% by echocardiogram
- Not pregnant or nursing
- Fertile patients must use effective contraception
- HIV negative
- Asthma or chronic obstructive pulmonary disease that does not require daily systemic
corticosteroids allowed
- No prior or concurrent autoimmune disease requiring management with systemic
immunosuppression, including any of the following:
- Inflammatory bowel disease
- Systemic vasculitis
- Scleroderma
- Psoriasis
- Multiple sclerosis
- Hemolytic anemia or immune-mediated thrombocytopenia
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Sjogren syndrome
- Sarcoidosis
- Other rheumatologic disease
- No other malignancies within the past 5 years, except carcinoma in situ of the cervix,
superficial nonmelanoma skin cancer, superficial bladder cancer, or tamoxifen-related
endometrial cancer that has been adequately treated
- No active major medical or psychosocial problems that could be complicated by study
participation
- No symptomatic intrinsic lung disease or extensive tumor involvement of the lungs
resulting in dyspnea at rest
- No uncontrolled medical problems
- No evidence of active acute or chronic infection
- No known severe hypersensitivity to trastuzumab, except mild to moderate infusion
reactions that are easily managed and do not recur
- No allergy to corn
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- More than 28 days since prior and no other concurrent chemotherapy, radiation therapy,
or biologic therapy (except trastuzumab)
- Concurrent endocrine therapy and supportive therapy with bisphosphonates allowed
- More than 28 days since prior and no other concurrent participation in an
investigational new drug trial
- More than 28 days since prior and no other concurrent systemic oral steroids
- Topical, ocular, and nasal steroids allowed
- No prior vaccination with the allogeneic GM-CSF-secreting breast tumor vaccine
| Maximum Eligible Age: | 120 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Toxicity as Assessed by Number of Grade 3 or 4 Adverse Events |
| Time Frame: | 3 years |
| Safety Issue: | |
| Description: | Number of grade 3 or 4 nonhematologic toxicity (except alopecia), or any grade 4 hematologic toxicity as defined by NCI CTCAE v3.0 |
Secondary Outcome Measures
| Measure: | Immune Priming in In-vivo Vaccine-site Biopsies |
| Time Frame: | 3 years |
| Safety Issue: | |
| Description: | |
| Measure: | Enumeration of CD8+ T Cells Specific for hTERT by ELISPOT |
| Time Frame: | 3 years |
| Safety Issue: | |
| Description: | |
| Measure: | Characterization of the T-cell Memory Pool Pre- and Post-vaccination |
| Time Frame: | 3 years |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
Trial Keywords
- stage IV breast cancer
- male breast cancer
Last Updated
April 24, 2019
