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Topical Imiquimod and Abraxane in Treating Patients With Advanced Breast Cancer

This study has been completed.
ClinicalTrials.gov Identifier:
First Posted: January 14, 2009
Last Update Posted: December 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mary (Nora) Disis, University of Washington
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: Intervention Model: Single Group Assignment
Masking: None (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:

Further study details as provided by Mary (Nora) Disis, University of Washington:

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 ]

    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).

    Evaluation of target lesions per modified WHO response criteria:

    • Complete response (CR): complete clearance (100%) of target lesion(s)
    • Partial response (PR): ≥ 50% decrease in target lesion size
    • Stable disease (SD): < 50% decrease in target lesion size
    • Progressive (PD): ≥ 25% increase in target lesion size Overall Response Rate (ORR) determined at end of study treatment which was 1 week after cycle #3, unless patient was withdrawn from study. If patient was withdrawn from study, then ORR was determined after their last cycle of treatment received.

  • 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 ]

    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 for the time frame below.

    Patients had a physical exam, per the time frame below, where the patient would be asked if they experienced any events under the following CTCAE categories:

    Constitutional (Fatigue) Neurological (Neuropathy (sensory or motor)) Cardiac (Arrhythemia) Pulmonary (Cough, Pharyngitis) GI (Constipation, Diarrhea, Mucositis, Vomiting) Dermatology (Ulceration, Hairloss/alopecia) Pain (Headache, other pain) Syndrome (Flu-like) Visual Changes Hearing/Auditory Edema Other (General)

    In addition they were asked the severity of the event so that a clinician could grade the event.

  • Pathologic Response by Immunohistochemical (IHC)as Assessed by Skin Punch Biopsy of the Target Lesion [ Time Frame: Pre-and post-treatment ]
    This is done by IHC staining reviewed by a pathologist. This is done by comparing the baseline to the post-treatment biopsy tissue. Yes equals absence of residual disease.

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 ]
    Peripheral blood will be obtained at baseline, after cycle 3 (end of study treatment) and at week 24 (end of study) to assess the immune response. A positive antigen-specific T cell immune response will be defined as a T cell precursor frequency more robust than 1:20,000 PBMC if the patients did not have a detectable response prior to treatment. In patients with a pre-existent immune response, the development of an immune response twice baseline will constitute augmentation.

  • 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 ]
    Incidence of reduction of serum TGF-beta levels as assessed by ELISA and correlation with Th1 adaptive immunity and clinical response is defined as a reduction of at least 25% from baseline value to the value measured at week 13.

Enrollment: 15
Study Start Date: December 2008
Study Completion Date: November 29, 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (biological therapy, chemo)
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:


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.


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.


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.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00821964

United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Principal Investigator: Lupe Salazar Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

Responsible Party: Mary (Nora) Disis, Principal Investigator, University of Washington
ClinicalTrials.gov Identifier: NCT00821964     History of Changes
Other Study ID Numbers: 6578
NCI-2010-00040 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
R01CA138521 ( U.S. NIH Grant/Contract )
131 ( Other Identifier: Tumor Vaccine Group )
First Submitted: January 13, 2009
First Posted: January 14, 2009
Results First Submitted: April 14, 2017
Results First Posted: June 28, 2017
Last Update Posted: December 6, 2017
Last Verified: October 2017

Keywords provided by Mary (Nora) Disis, University of Washington:
Breast Cancer
Stage IV

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Neoplasm Metastasis
Neoplasms by Site
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Interferon Inducers