Topical Imiquimod and Abraxane in Treating Patients With Advanced Breast Cancer

Stage IV Breast Cancer Clinical Trial

Official title:

Phase II Study of Topical Imiquimod and Weekly Abraxane for the Treatment of Breast Cancer Cutaneous Metastases

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00821964
• Other study ID #: 6578
• Secondary ID: NCI-2010-00040R0
• Status: Completed
• Phase: Phase 2
• First received: January 13, 2009
• Last updated: December 7, 2017
• Start date: December 2008
• Est. completion date: November 29, 2012

Study information

• Verified date: December 2017
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: November 29, 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Breast Neoplasms, Male
• Male Breast Cancer
• Neoplasm Metastasis
• Recurrent Breast Cancer
• Skin Metastases
• Stage IV Breast Cancer

Intervention

Drug:
• imiquimod
Given topically
• Abraxane
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Genetic:
• RNA analysis
Correlative studies

Other:
• immunoenzyme technique
Correlative studies

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anti-tumor Effects of Imiquimod as Assessed by Modified World Health Organization (WHO) Criteria	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.	Baseline and then every 4 weeks until week 24
Primary	Safety and Systemic Toxicity as Assessed by a Review of Medical History, Physical Exam, Systems, Performance Status, and Clinical Labs (CBC and CMP)	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.; Number of Participants with at Least 1 Adverse Event as Assessed by a Review of Medical History, Physical Exam, Systems, Performance Status, and Clinical Labs (CBC and CMP) 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.	Baseline and weeks 5, 9 13, 16, 20, and 24
Primary	Pathologic Response by Immunohistochemical (IHC)as Assessed by Skin Punch Biopsy of the Target Lesion	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.	Pre-and post-treatment
Secondary	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	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.	Baseline and at weeks 13 and 24
Secondary	Incidence of Reduction of Serum TGF-beta Levels as Assessed by ELISA and Correlation With Th1 Adaptive Immunity and Clinical Response	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.	Baseline and at weeks 13