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Breast CancerPhase 1NCT00093834

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

A Phase 1 study testing allogeneic GM-CSF-secreting breast cancer vaccine, cyclophosphamide and doxorubicin hydrochloride in people with Breast Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 120 years, women only
Conditions the study is for
Breast Cancer
What is being tested?
allogeneic GM-CSF-secreting breast cancer vaccine, cyclophosphamide and doxorubicin hydrochloride
Type of treatment
Vaccines
How many people
60 participants
Where
1 siteUnited States
Study dates
Jan 2004to Aug 2008
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231-2410

Other trials in United States

About this study

Official title: 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

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.

Read the 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
Being tested
allogeneic GM-CSF-secreting breast cancer vaccine, cyclophosphamide, doxorubicin hydrochloride
Keywords
stage IV breast cancer, recurrent breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • allogeneic GM-CSF-secreting breast cancer vaccineBiological

    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

  • cyclophosphamideDrug

    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 hydrochlorideDrug

    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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 4 years

  2. 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

    Measured: 4 years

  3. 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

    Measured: 4 years

  4. 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

    Measured: 4 years

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

    Measured: 4 years

Secondary outcomes (1)

  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

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Oct 2004 (estimated)
  2. Study startJan 2004
  3. Primary completionAug 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00093834
Sponsor's protocol ID
J0085 CDR0000391826
Other IDs
R01CA093714, P30CA006973, JHOC-J0085, JHOC-RPN-01012502, JHOC-RAC-0304-578
Status last verified
Jun 2023
First submitted
6 Oct 2004
Last updated
3 Jul 2023
Results posted
No

Publications

  • 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.

    PubMed 15018740

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing allogeneic GM-CSF-secreting breast cancer vaccine, cyclophosphamide and doxorubicin hydrochloride in people with Breast Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 4 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00093834, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2023.

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