This phase I/II trial studies the side effects of imiquimod, cyclophosphamide, and radiation therapy and to see how well they work in treating patients with breast cancer that has spread to the skin. Biological therapies, such as imiquimod, may stimulate the immune system in different ways and stop tumor cells from growing. Low dose cyclophosphamide works as an immunomodulatory agent to improve anti-tumor response. Radiation therapy uses high energy x-rays to kill tumor cells. Radiation therapy may help imiquimod work better by making tumor cells more sensitive to the drug. Giving imiquimod together with cyclophosphamide and radiation therapy may kill more tumor cells.
Additional locations may be listed on ClinicalTrials.gov for NCT01421017.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To estimate the systemic tumor response of topical imiquimod (IMQ) and concurrent local radiation therapy (RT) in breast cancer patients with cutaneous metastases.
II. To estimate the systemic tumor response of topical IMQ and concurrent local RT in breast cancer patients with cutaneous metastases receiving immunomodulatory cyclophosphamide.
III. To estimate the systemic tumor response of local RT in breast cancer patients with metastatic disease receiving immunomodulatory cyclophosphamide.
SECONDARY OBJECTIVES:
I. To determine the local tumor response of the combination of IMQ+RT.
II. To determine the safety of the combination of IMQ+RT, cyclophosphamide (CTX)/RT and CTX/IMQ/RT.
III. To examine whether IMQ+RT augments tumor specific T cell immunity and induces a tumor microenvironment signature consistent with immunological rejection.
IV. To explore treatment-induced changes of circulating immune cell subsets including T-regulatory cells (Treg).
OUTLINE: Skin metastases are divided into two areas (A) and (B) for different treatment.
Patients undergo radiation therapy* on days 1, 3, 5, 8 and 10 and apply topical imiquimod on days 1-5 of each week for total of 8 weeks in the absence of disease progression or unacceptable toxicity. This treatment is closed as of 6/9/2014.
Or:
Patients receive a single dose of cyclophosphamide intravenously (IV). Beginning one week later, patients undergo radiation therapy* on days 1, 3, 5, 8 and 10 and apply topical imiquimod on days 1-5 of each week for total of 8 weeks in the absence of disease progression or unacceptable toxicity.
Or:
Patients with multiple metastases (skin involvement not required) receive a single dose of cyclophosphamide IV. Beginning one week later, patients undergo radiation therapy to one site on days 1, 3, 5, 8 and 10 in the absence of disease progression or unacceptable toxicity and rest for additional 6 weeks.
Patients without clinically significant progression may complete additional courses.
*NOTE: Radiation therapy is applied only to Area A.
After completion of study treatment, patients are followed up periodically.
Lead OrganizationLaura and Isaac Perlmutter Cancer Center at NYU Langone
Principal InvestigatorSylvia Adams
