Topical Imiquimod and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced Breast Cancer - Full Text View

Sponsors and Collaborators:	Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00821964

Purpose

RATIONALE: Biological therapies, such as imiquimod, may stimulate the immune system to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving imiquimod together with paclitaxel albumin-stabilized nanoparticle formulation may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects of giving topical imiquimod together with paclitaxel albumin-stabilized nanoparticle formulation and to see how well it works in treating patients with advanced breast cancer.

Condition	Intervention	Phase
Breast Cancer Metastatic Cancer	Drug: imiquimod Drug: paclitaxel albumin-stabilized nanoparticle formulation Genetic: RNA analysis Other: immunoenzyme technique Other: laboratory biomarker analysis	Phase II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Paclitaxel S 26308

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
Official Title:	Phase II Study of Topical Imiquimod and Weekly Abraxane for the Treatment of Breast Cancer Cutaneous Metastases

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety and systemic toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
Response as assessed by modified WHO criteria at baseline and then every 4 weeks until week 24 [ Designated as safety issue: No ]
Pathologic response as assessed by skin punch biopsy before and after treatment [ Designated as safety issue: No ]

Secondary Outcome Measures:

Endogenous immunity to common breast tumor antigens (i.e., HER2, IGFBP-2, Topoisomerase II-α, and p53) as assessed by IFN-γ ELISPOT assay at baseline, at week 12, and at week 24 [ Designated as safety issue: No ]
Circulating TGF-β levels in serum samples as assessed by ELISA at baseline, at week 12, and at week 24 [ Designated as safety issue: No ]

Estimated Enrollment:	15
Study Start Date:	February 2009
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To evaluate the safety of topical imiquimod and paclitaxel albumin-stabilized nanoparticle formulation in patients with advanced stage refractory breast cancer with recurrent chest wall disease or cutaneous metastasis.
To evaluate the antitumor effects of this regimen in these patients.

Secondary

To examine whether treatment with this regimen augments endogenous tumor-specific immunity in these patients.
To assess the effect of this regimen on circulating TGF-β levels in these patients.

OUTLINE: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15 and apply topical imiquimod to cutaneous lesions once daily on days 1-4, 8-12, 15-18, and 22-25. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline, after course 3, and after completion of the study for correlative immunological analyses. Samples are assessed for endogenous immunity to common breast tumor antigens (i.e., HER2, IGFBP-2, topoisomerase II-α, and p53) by IFN-γ ELISPOT, circulating TGF-β levels by ELISA, and global mRNA expression by RNA analysis. Patients also undergo measurement, photo documentation, and punch biopsies of cutaneous lesions of lesions periodically for evaluation of response.

After completion of study treatment, patients are followed at 4, 8, and 12 weeks.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of breast cancer
- Advanced stage disease
Refractory, progressive or relapsed disease following standard therapy with chemotherapy and/or surgery, and/or radiotherapy
Measurable bidimensional chest wall disease and/or cutaneous metastatic lesions

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
WBC ≥ 3,000/μL
ANC ≥ 1,000/μL
Platelet count > 100,000/μL
Serum creatinine < 2.0 mg/dL
ALT and AST < 2 times upper limit of normal (ULN)
Total bilirubin < 2 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 1 month after completion of study treatment
Recovered from major infections and, in the opinion of the investigator, has no significant active concurrent medical illness that would preclude study treatment
No peripheral neuropathy ≥ grade 2
No active autoimmune disease
No prior allergic reactions to taxanes

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from major surgical procedures
At least 14 days since prior chemotherapy
At least 30 days since prior local radiotherapy and/or systemic steroids
Concurrent bisphosphonates, trastuzumab (Herceptin®), and/or hormonal therapy allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00821964

Locations

United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Recruiting
Seattle, Washington, United States, 98109-1024
Contact: Nicole Bates 206-543-6620

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Lupe G. Salazar, MD

Fred Hutchinson Cancer Research Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Fred Hutchinson Cancer Research Center ( Lupe G. Salazar )
Study ID Numbers:	CDR0000632200, UWCC-6578, FHCRC-6578, IR-6578
Study First Received:	January 13, 2009
Last Updated:	April 18, 2009
ClinicalTrials.gov Identifier:	NCT00821964 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage IV breast cancer
recurrent breast cancer
skin metastases
male breast cancer

Study placed in the following topic categories:

Skin Diseases
Immunologic Factors
Interferons
Adjuvants, Immunologic
Breast Neoplasms
Imiquimod
Antimitotic Agents
Breast Cancer, Male

Recurrence
Breast Neoplasms, Male
Paclitaxel
Tubulin Modulators
Neoplasm Metastasis
Antineoplastic Agents, Phytogenic
Breast Diseases

Additional relevant MeSH terms:

Interferon Inducers
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Skin Diseases
Antineoplastic Agents
Mitosis Modulators
Physiological Effects of Drugs
Adjuvants, Immunologic
Breast Neoplasms
Imiquimod
Antimitotic Agents

Pharmacologic Actions
Neoplasms
Neoplastic Processes
Neoplasms by Site
Pathologic Processes
Paclitaxel
Therapeutic Uses
Tubulin Modulators
Neoplasm Metastasis
Antineoplastic Agents, Phytogenic
Breast Diseases

ClinicalTrials.gov processed this record on May 06, 2009