Imiquimod for Breast Cancer Patients With Chest Wall Recurrence or Skin Metastases

Breast Cancer Clinical Trial

Official title:

Phase II Evaluation of Imiquimod, a Topical Toll-like Receptor 7 (TLR7) Agonist in Breast Cancer Patients With Chest Wall Recurrence or Skin Metastases

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00899574
• Other study ID #: NYU 09-0225
• Status: Completed
• Phase: Phase 2
• First received: May 11, 2009
• Last updated: November 6, 2015
• Start date: May 2009
• Est. completion date: June 2013

Study information

• Verified date: November 2015
• Source: New York University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to determine the safety and efficacy of Imiquimod, a Toll-like receptor 7 agonist in breast cancer (for chestwall recurrences or metastases to the skin).

Description:

TLR agonists are novel agents for cancer therapy which modify the immune response. Imiquimod, a synthetic TLR7 agonist has proven immunomodulatory activity when applied topically, leading to clearance of human papilloma virus (HPV)-induced genital warts and primary skin malignancies. Its effects will now be examined in breast cancer metastatic to the skin. If effective, it will add a relatively non-toxic approach to the treatment armamentarium for this patient population frequently resistant to conventional therapies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: June 2013
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with biopsy-confirmed breast cancer (prior histological documentation is acceptable).

• Patients with measurable skin metastases (chest wall recurrence and/or non-chest wall skin metastases are eligible).

• Skin metastases not suitable for or patient refusing definitive surgical resection and radiation.

• (Cohort 1) Concurrent systemic cancer therapy (hormones, biologics or chemotherapy) is allowed if distant metastases have been non-progressing (stable or responding) on that regimen for > or = 12 weeks and skin metastases are non-responsive (stable or progressing) as assessed by the investigator.

(Cohort 2) Any concurrent systemic therapy is allowed

• Age at least 18 years.

• Eastern Cooperative Oncology Group (ECOG) performance status < or = 2.

• Patients must have biopsy-accessible tumor (skin metastases) and agree to biopsies required by protocol.

• Patients must have adequate organ and bone marrow function as defined below:

• absolute neutrophil count > or = 1,500/microliter

• hemoglobin > or = 9.5 grams/deciliter

• platelets >or = 75,000/microliter

• total bilirubin < or = 1.5 X institutional upper limit of normal

• Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) < or = 2.5X institutional upper limit of normal

• creatinine < or = 1.5 X institutional upper limit of normal

• Informed consent.

Exclusion Criteria:

• Brain metastases unless resected or irradiated and stable > or = 8 weeks.

• Treatment with other investigational agents.

• Patients who have received radiotherapy, high-potency corticosteroids, intralesional therapy, laser therapy or surgery other than biopsy to the target area within 4 weeks prior to first dosing of study agent.

• Patients who have received hyperthermia to the target area within 10 weeks prior to first dosing of study agent.

• Patients with an uncontrolled bleeding disorder.

• Patients who will be therapeutically anticoagulated with heparins or coumadin at the time of the biopsy (they are eligible if anticoagulation can be held prior to biopsy as per investigator). Patients on aspirin and other platelet agents are eligible.

• Patients with known immunodeficiency or receiving immunosuppressive therapies.

• History of allergic reactions to imiquimod or its excipients.

• Uncontrolled intercurrent medical illness or psychiatric illness/social situations that would limit compliance with study requirements.

• Pregnancy or lactation.

• Women of childbearing potential not using a medically acceptable means of contraception.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Imiquimod
Each treatment cycle consists of 8 weeks. Weeks 1-8: day 1-5 of each week: 1 packet imiquimod 5% cream applied overnight, day 6-7 of each week: rest period. Patients with responding or stable local disease (non-progressors) may continue to receive treatment following the same schedule (as outlined above for the first cycle) until complete tumor regression, unacceptable toxicity or progression of disease.

Locations

Country	Name	City	State
United States	NYU Cancer Institute	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
New York University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (1)

Adams S, Kozhaya L, Martiniuk F, Meng TC, Chiriboga L, Liebes L, Hochman T, Shuman N, Axelrod D, Speyer J, Novik Y, Tiersten A, Goldberg JD, Formenti SC, Bhardwaj N, Unutmaz D, Demaria S. Topical TLR7 agonist imiquimod can induce immune-mediated rejection — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response (Complete Clinical Response+ Partial Response)	This is defined as percentage of patients who achieved complete clinical response or partial response at end of cycle 1 of treatment. The tumor size will be measured as lesion surface area (region of interest, ROI). The response to the treatment is then evaluated as a function of post-treatment over pre-treatment ROI, expressed in percentage. Response criteria for this study are based on European Organisation for Research and Treatment of Cancer definitions for chest wall tumors: complete clinical response: absence of any detectable residual disease; partial response: <50% of ROI change.	9 weeks	No
Secondary	Clinical Benefits	This outcome measure is defined as number of patients with improvement of symptoms after 8 weeks of treatment.	9 weeks	No