Cyclophosphamide and Vaccine Therapy With or Without Trastuzumab in Treating Patients With Metastatic Breast Cancer
This study is currently recruiting participants.
Verified November 2012 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Sidney Kimmel Comprehensive Cancer Center
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00971737
First received: September 3, 2009
Last updated: November 15, 2012
Last verified: November 2012
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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.
| Condition | Intervention | Phase |
|---|---|---|
|
Breast Cancer |
Biological: allogeneic GM-CSF-secreting breast cancer vaccine Biological: trastuzumab Drug: cyclophosphamide |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:
Primary Outcome Measures:
- Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
- Progression-free survival at 6 months [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- HER-2/neu-specific immune responses [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Pharmacodynamics of peripheral CD4+CD25+ regulatory T cells [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Immune priming in in-vivo vaccine-site biopsies [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Enumeration of CD8+ T cells specific for hTERT by ELISPOT [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Characterization of the T-cell memory pool pre- and post-vaccination [ Time Frame: 3 years ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 60 |
| Study Start Date: | July 2009 |
| Estimated Primary Completion Date: | July 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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.
|
Biological: allogeneic GM-CSF-secreting breast cancer vaccine
Given intradermally
Drug: cyclophosphamide
Given IV
|
|
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.
|
Biological: allogeneic GM-CSF-secreting breast cancer vaccine
Given intradermally
Biological: trastuzumab
Given IV
Drug: cyclophosphamide
Given IV
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00971737
Locations
| United States, Maryland | |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting |
| Baltimore, Maryland, United States, 21231-2410 | |
| Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce 410-955-8804 jhcccro@jhmi.edu | |
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
| Principal Investigator: | Leisha A. Emens, MD, PhD | Sidney Kimmel Comprehensive Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | Sidney Kimmel Comprehensive Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00971737 History of Changes |
| Other Study ID Numbers: | J0947 CDR0000653173, P30CA006973, JHOC-J0947, NA_00024527, GENENTECH-JHOC-J0947 |
| Study First Received: | September 3, 2009 |
| Last Updated: | November 15, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
|
stage IV breast cancer male breast cancer |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Cyclophosphamide Trastuzumab Immunosuppressive Agents Immunologic Factors |
Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists |
ClinicalTrials.gov processed this record on May 22, 2013