Vaccine Therapy With or Without Cyclophosphamide and Doxorubicin in Women With Stage IV Breast Cancer

NCT00093834 | Completed Phase 1

• 6 other identifiers: J0085 CDR0000391826R01CA093714P30CA006973JHOC-J0085JHOC-RPN-01012502JHOC-RAC-0304-578
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Vaccines made from a person's tumor cells may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide and doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining vaccine therapy with cyclophosphamide and doxorubicin may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of cyclophosphamide and doxorubicin when given with vaccine therapy in treating women with stage IV breast cancer.

Conditions

Breast Cancer

Keywords

stage IV breast cancer; recurrent breast cancer

Outcome Measures

Primary Outcomes (5)

• Toxicity of vaccine w/ & w/o cyclophosphamide+doxorubicin by history and phys. exam. at 28-42 days after each vaccination, 56-84 days after third vaccination, 6 months after first vaccination, and annually after first vaccination

  4 years

• Toxicity of vaccine w/ & w/o cyclophosphamide+doxorubicin by CBC w/ differential at days 7, 14, 21, and 28-42 days after each vaccination, 56-84 days after third vaccination, 6 months after first vaccination, and annually after first vaccination

  4 years

• Toxicity of vaccine w/ & w/o cyclophosphamide+doxorubicin by comprehensive metabolic panel at day 7 and 28-42 days after each vaccination, 56-84 days after third vaccination, 6 months after first vaccination, and annually after first vaccination

  4 years

• Immune resp. of HER-2/neu by serum antibody titers, delayed hypersensitivity to HER-2/neu-derived peptides, and CD4+ T-cell resp. by ELISPOT at days 28-42 after each vaccination and days 56-84 after third vaccination

  4 years

• Immune responses by immunohistochemical analysis of vaccine site biopsies at days 3 and 7 after the first and third vaccinations

  4 years

Secondary Outcomes (1)

• Time to disease progression by history and physical examination, computed tomography, bone scans, and tumor markers as appropriate at days 28-42 after third and fourth vaccinations and days 56-84 after third vaccination

  4 years

Interventions

allogeneic GM-CSF-secreting breast cancer vaccine BIOLOGICAL

The first three patients will receive a dose of 5 X 107 cells, and the next three will receive a dose of 5 X 108 cells. Then, if these two doses of vaccine alone are found to be safe, a fixed vaccine dose of 5 X 108 cells will be tested in combination with chemotherapy based on the safety of the allogeneic breast vaccine alone and the safety and bioactivity of a dose of 5 X 108 cells in the allogeneic pancreatic vaccine trial

cyclophosphamide DRUG

This trial will be a dose ranging study of a fixed sequence of drug doses in a three by three factorial matrix modeled after the theories of Plackett and Burman (Plackett et al., 1946), and is designed to determine the doses of CY and DOX that maximize the immunologic response to vaccination

doxorubicin hydrochloride DRUG

This trial will be a dose ranging study of a fixed sequence of drug doses in a three by three factorial matrix modeled after the theories of Plackett and Burman (Plackett et al., 1946), and is designed to determine the doses of CY and DOX that maximize the immunologic response to vaccination

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma of the breast * Stage IV disease * Stable disease for ≥ 28 days * Measurable or evaluable disease OR no evidence of disease * Not eligible for potentially curative therapy * Adequately treated CNS metastases are allowed * Hormone receptor status: * Not specified * HER-2/neu status: * Not specified PATIENT CHARACTERISTICS: Age * 18 and over Sex * Female Menopausal status * Not specified Performance status * ECOG 0-1 Life expectancy * Not specified Hematopoietic * Absolute neutrophil count \> 1,000/mm\^3 * Platelet count \> 100,000/mm\^3 Hepatic * Bilirubin ≤ 2.0 mg/dL (unless due to Gilbert's syndrome) * AST and ALT ≤ 2 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 5 times ULN Renal * Creatinine \< 2.0 mg/dL Cardiovascular * Ejection fraction ≥ 45% by echocardiogram or MUGA Pulmonary * Asthma or chronic obstructive pulmonary disease allowed provided daily systemic corticosteroid therapy is not required Immunologic * No active autoimmune disease requiring systemic immunosuppressive therapy, including any of the following: * Inflammatory bowel disease * Systemic vasculitis * Scleroderma * Psoriasis * Multiple sclerosis * Hemolytic anemia * Immune-mediated thrombocytopenia * Rheumatoid arthritis * Systemic lupus erythematosus * Sjögren's syndrome * Sarcoidosis * Other rheumatologic disease * HIV negative * No active acute or chronic infection * No allergy to corn Other * No other malignancy within the past 5 years except carcinoma in situ of the cervix, superficial nonmelanoma skin cancer, or superficial bladder cancer * No active major medical or psychosocial problem that would preclude study participation * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy * More than 28 days since prior biologic therapy * No other concurrent biologic therapy, including trastuzumab (Herceptin®) Chemotherapy * Prior adjuvant chemotherapy allowed * Prior doxorubicin and cyclophosphamide allowed * Prior doxorubicin dose combined with planned study therapy dose must not exceed a lifetime cumulative dose of ≥ 450 mg/m\^2 * More than 28 days since prior systemic chemotherapy * No other concurrent systemic chemotherapy Endocrine therapy * More than 28 days since prior systemic corticosteroids * Concurrent hormonal or endocrine therapy allowed * No concurrent systemic corticosteroids Radiotherapy * More than 28 days since prior radiotherapy * No concurrent radiotherapy Surgery * Not specified Other * More than 28 days since prior participation in another investigational drug trial * No other concurrent investigational drugs * Concurrent bisphosphonates allowed

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Related Publications (1)

• Emens LA, Armstrong D, Biedrzycki B, Davidson N, Davis-Sproul J, Fetting J, Jaffee E, Onners B, Piantadosi S, Reilly RT, Stearns V, Tartakovsky I, Visvanathan K, Wolff A. A phase I vaccine safety and chemotherapy dose-finding trial of an allogeneic GM-CSF-secreting breast cancer vaccine given in a specifically timed sequence with immunomodulatory doses of cyclophosphamide and doxorubicin. Hum Gene Ther. 2004 Mar;15(3):313-37. doi: 10.1089/104303404322886165. No abstract available.

  PMID: 15018740 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Leisha A. Emens, MD, PhD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2004
• First Posted: October 8, 2004
• Study Start: January 1, 2004
• Primary Completion: August 1, 2008
• Last Updated: July 3, 2023

Record last verified: 2023-06

Locations

US (1)