Topical Imiquimod and Abraxane in Treating Patients With Advanced Breast Cancer
|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 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|
- 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Overall Response Rate (ORR) determined at end of study treatment which was 1 week after cycle #3, unless patient was withdrawn from study. If patient was withdrawn from study, then ORR was determined after their last cycle of treatment received.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.
- 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 and 24 ]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.
|Study Start Date:||December 2008|
|Study Completion Date:||November 29, 2012|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
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.
Other Names:Drug: Abraxane
Other Names:Other: laboratory biomarker analysis
Correlative studiesGenetic: RNA analysis
Correlative studiesOther: immunoenzyme technique
Other Name: immunoenzyme techniques
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00821964
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Lupe Salazar||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|