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Imiquimod, Cyclophosphamide, and Radiation Therapy in Treating Patients with Breast Cancer with Skin Metastases

Trial Status: Closed to Accrual

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.

Inclusion Criteria

  • Patients with biopsy-confirmed breast cancer
  • Patients with at least one measurable skin metastases and distant, measurable metastases (outside of skin) by Response Evaluation Criteria in Solid Tumors (RECIST); for patients without distant measurable metastases, an area of the skin metastases designated to not receive local therapy can be substituted; patients with multiple (>= 2) metastatic sites (skin involvement not required), with at least one site measurable by RECIST, will be eligible for the CTX/RT cohort
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Patients with skin metastases must agree to tumor fine-needle aspiration (FNA) required by protocol
  • Concurrent systemic cancer therapy (hormones, biologics or chemotherapy) can be continued if distant metastases are non-responsive (i.e. no complete response [CR] or partial response [PR]) on that regimen for >= 8 weeks as assessed by the investigator
  • 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
  • Aspartate aminotransferase (AST) =< 2.5 x institutional upper limit of normal
  • Alanine aminotransferase (ALT) < 2.5 x institutional upper limit of normal
  • Creatinine =< 2 x institutional upper limit of normal if patient has chronic renal insufficiency and creatinine has been stable x > 4 months
  • Informed consent

Exclusion Criteria

  • Brain metastases unless resected or irradiated and stable >= 4 weeks
  • Concurrent treatment with other investigational agents
  • 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
  • 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 (with skin metastases only) 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

New York

New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: CLOSED_TO_ACCRUAL
Contact: Sylvia Adams
Phone: 212-731-5795
NYP / Weill Cornell Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Silvia Chiara Formenti
Phone: 212-746-1006

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.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Laura and Isaac Perlmutter Cancer Center at NYU Langone

Principal Investigator
Sylvia Adams

  • Primary ID NYU 11-00598
  • Secondary IDs NCI-2011-02879, 11-00598
  • Clinicaltrials.gov ID NCT01421017