Topical Imiquimod and Abraxane in Treating Patients With Advanced Breast Cancer - Full Text View

Sponsor:	Fred Hutchinson Cancer Research Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00821964

Purpose

This phase II trial is studying the side effects of giving topical imiquimod together with Abraxane (paclitaxel albumin-stabilized nanoparticle formulation) to see how well it works in treating patients with advanced breast cancer. Biological therapies, such as imiquimod, may stimulate the immune system to kill tumor cells. Drugs used in chemotherapy, such as Abraxane, 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 Abraxane may kill more tumor cells.

Condition	Intervention	Phase
Male Breast Cancer Recurrent Breast Cancer Skin Metastases Stage IV Breast Cancer	Drug: imiquimod Drug: Abraxane Other: laboratory biomarker analysis Genetic: RNA analysis Other: immunoenzyme technique	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase II Study of Topical Imiquimod and Weekly Abraxane for the Treatment of Breast Cancer Cutaneous Metastases

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Male Breast Cancer

Drug Information available for: Paclitaxel Ribonucleic acid Imiquimod

U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:

Anti-tumor effects of imiquimod as assessed by modified World Health Organization (WHO) criteria [ Time Frame: Baseline and then every 4 weeks until week 24 ] [ Designated as safety issue: No ]
Tumor responses will be determined using the sum of the products of the largest perpendicular dimensions. Target lesions will be evaluated by the following response criteria: complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD).
Safety and systemic toxicity as assessed by a review of medical history, physical exam, systems, performance status, and clinical labs (CBC and CMP) [ Time Frame: Baseline and weeks 5, 9 13, 16, 20, and 24 ] [ Designated as safety issue: Yes ]
Evaluated according to the Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and monitoring of adverse events will be done per Food and Drug Administration (FDA) and National Cancer Institute (NCI) guidelines
Pathologic response as assessed by skin punch biopsy [ Time Frame: Pre-and post-treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Endogenous immunity to common breast tumor antigens (HER2, IGFBP-2, Topoisomerase II-alpha, and p53) in peripheral blood as assessed by IFN-gamma and ELISPOT assay [ Time Frame: Baseline and at weeks 13 and 24 ] [ Designated as safety issue: No ]
Incidence of reduction of serum TGF-beta levels as assessed by ELISA and correlation with Th1 adaptive immunity and clinical response [ Time Frame: Baseline and at weeks 13 and 24 ] [ Designated as safety issue: No ]

Estimated Enrollment:	15
Study Start Date:	December 2008
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment (biological therapy, chemotherapy) Patients receive Abraxane IV over 30 minutes on days 1, 8, and 15 and apply topical imiquimod to cutaneous lesions QD on days 1-4, 8-11, 15-18, and 22-25. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.	Drug: imiquimod Given topically Other Names: Aldara IMQ R 837 Drug: Abraxane Given IV Other Names: Albumin-Stabilized Nanoparticle Paclitaxel nab paclitaxel nab-paclitaxel nanoparticle albumin-bound paclitaxel Nanoparticle Paclitaxel paclitaxel albumin-stabilized nanoparticle formulation Other: laboratory biomarker analysis Correlative studies Genetic: RNA analysis Correlative studies Other: immunoenzyme technique Correlative studies Other Name: immunoenzyme techniques

Arms

Assigned Interventions

Experimental: Treatment (biological therapy, chemotherapy)

Patients receive Abraxane IV over 30 minutes on days 1, 8, and 15 and apply topical imiquimod to cutaneous lesions QD on days 1-4, 8-11, 15-18, and 22-25. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

Drug: imiquimod

Given topically

Other Names:

Aldara
IMQ
R 837

Drug: Abraxane

Given IV

Other Names:

Albumin-Stabilized Nanoparticle Paclitaxel
nab paclitaxel
nab-paclitaxel
nanoparticle albumin-bound paclitaxel
Nanoparticle Paclitaxel
paclitaxel albumin-stabilized nanoparticle formulation

Other: laboratory biomarker analysis

Correlative studies

Genetic: RNA analysis

Correlative studies

Other: immunoenzyme technique

Correlative studies

Other Name: immunoenzyme techniques

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the safety of chemoimmunotherapy with topical imiquimod and Abraxane in breast cancer patients with recurrent chest wall disease or cutaneous metastasis.

II. To evaluate the anti-tumor effects of chemoimmunotherapy with topical imiquimod and Abraxane in breast cancer patients with recurrent chest wall disease or cutaneous metastasis.

SECONDARY OBJECTIVES:

I. To examine whether treatment with chemoimmunotherapy consisting of topical imiquimod and Abraxane augments endogenous tumor specific immunity.

II. To assess the effect of chemoimmunotherapy on circulating transforming growth factor (TGF)-beta levels.

OUTLINE:

Patients receive Abraxane intravenously (IV) over 30 minutes on days 1, 8, and 15 and apply topical imiquimod to cutaneous lesions once daily (QD) on days 1-4, 8-11, 15-18, and 22-25. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1, 4, 8, and 12 weeks.

Eligibility

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

Criteria

Inclusion Criteria:

Patients with advanced stage refractory breast cancer
Progressive or relapsed disease following standard therapy with chemotherapy and/or surgery, and/or radiation
Patients must have measurable (bi-dimensional) chest wall disease and/or cutaneous metastatic lesions
Patients must be at least 7 days from last chemotherapy and 30 days from local radiotherapy and/or systemic steroids
Patients on bisphosphonates, trastuzumab, lapatinib and/or hormonal therapy are eligible
White blood cell count >= 1000/ul
Absolute neutrophil count (ANC) >= 1200/ul
Platelets > 75,000/ul
Serum creatinine =< 2.0 mg/dL, a creatinine clearance > 60 ml/min
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2 X upper limit normal (ULN)
Total bilirubin < 2 X ULN
Patients must have a Performance Status Score (Eastern Cooperative Oncology Group [ECOG] Scale) =< 2
Patients must have recovered from major infections and/or surgical procedures and, in the opinion of the investigator, not have a significant active concurrent medical illness precluding protocol treatment
Men and women of reproductive ability must agree to contraceptive use during the study and for 1 month after imiquimod/Abraxane treatment is discontinued

Exclusion Criteria:

Patients with prior allergic reaction to taxanes
Patients with any clinically significant active autoimmune disease requiring active treatment with systemic steroids or other immunomodulators
Pregnant or breast-feeding women
Patients with peripheral neuropathy >= Grade 2

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
Contact: Stephanie Parker 206-543-6620 TVGTrial@uw.edu
Principal Investigator: Lupe G. Salazar

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Lupe Salazar

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

More Information

No publications provided

Responsible Party:	Salazar, Lupe, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier:	NCT00821964 History of Changes
Other Study ID Numbers:	6578, NCI-2010-00040, R01CA138521, 131
Study First Received:	January 13, 2009
Last Updated:	January 17, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Fred Hutchinson Cancer Research Center:

Breast Cancer
Stage IV
cream
topical

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasm Metastasis
Skin Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Imiquimod
Paclitaxel

Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Interferon Inducers
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 23, 2012