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Topical Imiquimod and Abraxane in Treating Patients With Advanced Breast Cancer

Primary Purpose

Male Breast Cancer, Recurrent Breast Cancer, Skin Metastases

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
imiquimod
Abraxane
laboratory biomarker analysis
RNA analysis
immunoenzyme technique
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Male Breast Cancer focused on measuring Breast Cancer, Stage IV, cream, topical

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (biological therapy, chemo)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.
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.

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
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
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.

Full Information

First Posted
January 13, 2009
Last Updated
December 7, 2017
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00821964
Brief Title
Topical Imiquimod and Abraxane in Treating Patients With Advanced Breast Cancer
Official Title
Phase II Study of Topical Imiquimod and Weekly Abraxane for the Treatment of Breast Cancer Cutaneous Metastases
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
December 2008 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 29, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Male Breast Cancer, Recurrent Breast Cancer, Skin Metastases, Stage IV Breast Cancer
Keywords
Breast Cancer, Stage IV, cream, topical

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (biological therapy, chemo)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
imiquimod
Other Intervention Name(s)
Aldara, IMQ, R 837
Intervention Description
Given topically
Intervention Type
Drug
Intervention Name(s)
Abraxane
Other Intervention Name(s)
Albumin-Stabilized Nanoparticle Paclitaxel, nab paclitaxel, nab-paclitaxel, nanoparticle albumin-bound paclitaxel, Nanoparticle Paclitaxel, paclitaxel albumin-stabilized nanoparticle formulation
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Genetic
Intervention Name(s)
RNA analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
immunoenzyme technique
Other Intervention Name(s)
immunoenzyme techniques
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Anti-tumor Effects of Imiquimod as Assessed by Modified World Health Organization (WHO) Criteria
Description
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.
Time Frame
Baseline and then every 4 weeks until week 24
Title
Safety and Systemic Toxicity as Assessed by a Review of Medical History, Physical Exam, Systems, Performance Status, and Clinical Labs (CBC and CMP)
Description
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.
Time Frame
Baseline and weeks 5, 9 13, 16, 20, and 24
Title
Pathologic Response by Immunohistochemical (IHC)as Assessed by Skin Punch Biopsy of the Target Lesion
Description
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.
Time Frame
Pre-and post-treatment
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Baseline and at weeks 13 and 24
Title
Incidence of Reduction of Serum TGF-beta Levels as Assessed by ELISA and Correlation With Th1 Adaptive Immunity and Clinical Response
Description
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.
Time Frame
Baseline and at weeks 13

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lupe Salazar
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
28114604
Citation
Salazar LG, Lu H, Reichow JL, Childs JS, Coveler AL, Higgins DM, Waisman J, Allison KH, Dang Y, Disis ML. Topical Imiquimod Plus Nab-paclitaxel for Breast Cancer Cutaneous Metastases: A Phase 2 Clinical Trial. JAMA Oncol. 2017 Jul 1;3(7):969-973. doi: 10.1001/jamaoncol.2016.6007.
Results Reference
derived

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Topical Imiquimod and Abraxane in Treating Patients With Advanced Breast Cancer

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