Cyclophosphamide and Vaccine Therapy With or Without Trastuzumab in Treating Patients With Metastatic Breast Cancer

Tracking Information
First Submitted Date ICMJE	September 3, 2009
First Posted Date ICMJE	September 4, 2009
Last Update Posted Date	September 25, 2015
Study Start Date ICMJE	July 2009
Estimated Primary Completion Date	March 2016 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: June 28, 2011)	Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: 3 years ]; Progression-free survival at 6 months [ Time Frame: 3 years ]; HER-2/neu-specific immune responses [ Time Frame: 3 years ]; Pharmacodynamics of peripheral CD4+CD25+ regulatory T cells [ Time Frame: 3 years ]
Original Primary Outcome Measures ICMJE; (submitted: September 3, 2009)	Toxicity as assessed by NCI CTCAE v3.0; Progression-free survival at 6 months; HER-2/neu-specific immune responses; Pharmacodynamics of peripheral CD4+CD25+ regulatory T cells
Change History	Complete list of historical versions of study NCT00971737 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: June 28, 2011)	Immune priming in in-vivo vaccine-site biopsies [ Time Frame: 3 years ]; Enumeration of CD8+ T cells specific for hTERT by ELISPOT [ Time Frame: 3 years ]; Characterization of the T-cell memory pool pre- and post-vaccination [ Time Frame: 3 years ]
Original Secondary Outcome Measures ICMJE; (submitted: September 3, 2009)	Immune priming in in-vivo vaccine-site biopsies; Enumeration of CD8+ T cells specific for hTERT by ELISPOT; Characterization of the T-cell memory pool pre- and post-vaccination
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Cyclophosphamide and Vaccine Therapy With or Without Trastuzumab in Treating Patients With Metastatic Breast Cancer
Official Title ICMJE	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
Brief Summary	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.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Breast Cancer
Intervention ICMJE	Biological: allogeneic GM-CSF-secreting breast cancer vaccine Given intradermally; Biological: trastuzumab Given IV; Drug: cyclophosphamide Given IV
Study Arms	Active Comparator: 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. Interventions: Biological: allogeneic GM-CSF-secreting breast cancer vaccine Drug: cyclophosphamide; Experimental: 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. Interventions: Biological: allogeneic GM-CSF-secreting breast cancer vaccine Biological: trastuzumab Drug: cyclophosphamide
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Unknown status
Estimated Enrollment ICMJE; (submitted: September 3, 2009)	60
Original Estimated Enrollment ICMJE	Same as current
Study Completion Date	Not Provided
Estimated Primary Completion Date	March 2016 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 120 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00971737
Other Study ID Numbers ICMJE	J0947 CDR0000653173; P30CA006973 ( U.S. NIH Grant/Contract ); JHOC-J0947; NA_00024527; GENENTECH-JHOC-J0947
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Sidney Kimmel Comprehensive Cancer Center
Study Sponsor ICMJE	Sidney Kimmel Comprehensive Cancer Center
Collaborators ICMJE	National Cancer Institute (NCI)
Investigators ICMJE	Principal Investigator: Leisha A. Emens, MD, PhD Sidney Kimmel Comprehensive Cancer Center
PRS Account	Sidney Kimmel Comprehensive Cancer Center
Verification Date	September 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP