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

NCT ID: NCT00093834

Last Updated: 2023-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-31

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.

Detailed Description

OBJECTIVES:

Primary

• Determine the safety of vaccination comprising allogeneic sargramostim (GM-CSF)-secreting breast cancer cells with or without immunomodulation using cyclophosphamide and doxorubicin in women with stage IV breast cancer.
• Determine the doses of cyclophosphamide and doxorubicin that maximize vaccine-induced immunity, in terms of immune response to HER2/neu, in patients treated with these regimens.
• Compare in vivo immune response induced by these regimens, as measured by immunohistochemical analysis of vaccine site biopsies from these patients, with responses seen in prior preclinical and clinical studies.

Secondary

• Determine the time to disease progression in patients treated with these regimens.

OUTLINE: This is a dose-finding study.

The first 6 patients receive 1 of 2 doses of vaccine comprising allogeneic sargramostim (GM-CSF)-secreting breast cancer cells intradermally (ID) on day 0. Subsequent patients receive cyclophosphamide IV on day -1, vaccine at the higher dose ID on day 0, and doxorubicin IV on day 7. Treatment in all patients repeats every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease after the third course receive a fourth course of treatment at approximately 4 months after completion of the third course.

Cohorts of 2-3 patients receive a fixed dose of vaccine in combination with escalating doses of doxorubicin and cyclophosphamide. Doses of cyclophosphamide and doxorubicin are escalated until an optimal dose of combination chemotherapy with a fixed dose of vaccine is achieved.

Patients are followed at 1 month and 4 months after completion of study therapy and then annually thereafter.

PROJECTED ACCRUAL: A total of 6-60 patients will be accrued for this study.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

cyclophosphamide

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

Intervention Type: DRUG

doxorubicin hydrochloride

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

Intervention Type: DRUG

allogeneic GM-CSF-secreting breast cancer vaccine

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Leisha A. Emens, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 15018740 (View on PubMed)

Other Identifiers

R01CA093714

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

JHOC-J0085

Identifier Type: -

Identifier Source: secondary_id

JHOC-RPN-01012502

Identifier Type: -

Identifier Source: secondary_id

JHOC-RAC-0304-578

Identifier Type: -

Identifier Source: secondary_id

J0085 CDR0000391826

Identifier Type: -

Identifier Source: org_study_id