Topical Imiquimod and Abraxane in Treating Patients With Advanced Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT00821964
First received: January 13, 2009
Last updated: August 13, 2014
Last verified: August 2014
  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:


Further study details as provided by 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 ] [ 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
Primary Completion Date: January 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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

No publications provided

Responsible Party: University of Washington
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: August 13, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Washington:
Breast Cancer
Stage IV
cream
topical

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

ClinicalTrials.gov processed this record on October 19, 2014