Toll-like Receptor (TLR) 7 Agonist and Radiotherapy for Breast Cancer With Skin Metastases

This study is currently recruiting participants.
Verified November 2013 by New York University School of Medicine
Information provided by (Responsible Party):
New York University School of Medicine Identifier:
First received: August 17, 2011
Last updated: November 7, 2013
Last verified: November 2013

The cell killing and immunostimulatory properties of two local treatment modalities, radiotherapy (RT) and Imiquimod (IMQ), may generate an effective immune response and lead to systemic control of breast cancer after local treatment of the cancer on the skin spread from the breast (skin metastases). This study is to find an optimal dose of IMQ in the first part and test the effectiveness of the combination treatment of RT and IMQ in patients with skin metastases from breast cancer in the second part.

Condition Intervention Phase
Breast Cancer
Metastatic Breast Cancer
Recurrent Breast Cancer
Radiation: Radiation
Drug: Imiquimod
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of TLR7 Agonist Imiquimod and Radiotherapy in Breast Cancer Patients With Chest Wall Recurrence or Skin Metastases

Resource links provided by NLM:

Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • systemic tumor response rates (CR+PR) at the time of best overall response (Ph II) [ Time Frame: 9 weeks from the strat of the treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • local tumor response rates (CCR+PR) at best overall response (Ph II) [ Time Frame: 9 weeks from the start of the treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 37
Study Start Date: August 2011
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IMQ+RT
At trial entry, all skin metastases will be divided into two areas (A) and (B) for differential treatment. Area A will receive IMQ + RT while area B will only receive IMQ. The size and location of cutaneous metastases for RT (area A) will be chosen by the radiation oncologist, to assure avoidance of overtreatment by radiation in pre-irradiated patients. All cutaneous metastases outside of area A will be included in area B.
Radiation: Radiation
Radiotherapy will be administered to Area A at a dose of 6 Gy given at five fractions on days 1, 3, 5, 8 and 10 (M-W-F-M-W) during a 8-week treatment cycle. All patients may continue to receive additional cycles (same schedule, RT given to a different cutaneous area, which may comprise all the prior area B), provided that patients wish to continue, are without clinically significant progression and further treatment may be beneficial in the opinion of the investigator
Drug: Imiquimod
Treatment with topical imiquimod 5% to all skin metastases (Areas A and B) starts the evening after the first radiation dose (day 1). IMQ treatment is given 5 days/week or Days 1, 3, 5/week for a total of 8 weeks (=1 cycle). The treatment dose is determined by tumor area: One single-use packet of imiquimod 5% (250 mg cream) per day is used for tumors <100cm^2, an additional package/d is added for each additional 100cm^2 area, not to exceed 6 packets/d. Patients self-apply a thin layer of IMQ 5% topically in the evening and wash it off the next morning (6-10 hours after initial application) with mild soap and water to remove any residual cream.
Other Name: ALDARA

Detailed Description:

This is a single arm, open label Phase I/II clinical trial to treat breast cancer with skin metastases (chest wall or other sites).

A brief Phase I part is conducted, to allow dose optimization in the event of unanticipated adverse events (3-3 design). In the Phase II part, efficacy is the primary endpoint. Twenty five patients will be enrolled to Phase II.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with biopsy-confirmed breast cancer.
  2. Patients with measurable skin metastases and distant, measurable metastases (outside of skin) by RECIST. For patients without distant measurable metastases, an area of the skin metastases designated to not receive local therapy can be substituted.
  3. Age >= 18 years.
  4. ECOG performance status 0-2.
  5. Patients must agree to tumor FNA required by protocol.
  6. Concurrent systemic cancer therapy (hormones, biologics or chemotherapy) can be continued if distant metastases are non-responsive (i.e. no CR or PR) on that regimen for >= 8 weeks as assessed by the investigator.
  7. Patients must have adequate organ and bone marrow function as defined below:

    • absolute neutrophil count >= 1,300/microliter
    • hemoglobin >= 9.0 grams/deciliter
    • platelets >= 75,000/microliter
    • total bilirubin =< 1.5 X institutional upper limit of normal
    • AST =< 2.5 X institutional upper limit of normal
    • ALT < 2.5 X institutional upper limit of normal
    • creatinine =< 1.5 X institutional upper limit of normal
  8. Informed consent.

Exclusion Criteria:

  1. Brain metastases unless resected or irradiated and stable >= 4 weeks.
  2. Concurrent treatment with other investigational agents.
  3. Patients who have received any local therapy (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.
  4. Patients who have received hyperthermia to the target area within 10 weeks prior to first dosing of study agent.
  5. Patients with an uncontrolled bleeding disorder.
  6. 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.
  7. Patients with known immunodeficiency or receiving immunosuppressive therapies.
  8. History of allergic reactions to imiquimod or its excipients.
  9. Uncontrolled intercurrent medical illness or psychiatric illness/social situations that would limit compliance with study requirements.
  10. Pregnancy or lactation.
  11. Women of childbearing potential not using a medically acceptable means of contraception.
  Contacts and Locations
Please refer to this study by its identifier: NCT01421017

Contact: Sylvia Adams, MD 212-263-6485
Contact: Maria Fenton-Kerimian, NP 212-731-5035

United States, New York
New York University Medical Center Recruiting
New York, New York, United States, 10016
Principal Investigator: Silvia Formenti, MD         
Sub-Investigator: Yelena Novik, MD         
Sub-Investigator: James Speyer, MD         
Sub-Investigator: Franco Muggia, MD         
Sub-Investigator: Ruth Oratz, MD         
Sub-Investigator: Nelly Huppert, MD         
Principal Investigator: Sylvia Adams, MD         
Sponsors and Collaborators
New York University School of Medicine
Principal Investigator: Sylvia Adams, MD New York University School of Medicine
  More Information

No publications provided

Responsible Party: New York University School of Medicine Identifier: NCT01421017     History of Changes
Other Study ID Numbers: NYU 11-00598, 1R01CA161891-01
Study First Received: August 17, 2011
Last Updated: November 7, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by New York University School of Medicine:
radiation therapy
combination therapy
immune response modifier

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Neoplasms by Site
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Interferon Inducers processed this record on April 17, 2014