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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by New York University School of Medicine
Sponsor:
Collaborator:
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT01421017
First received: August 17, 2011
Last updated: June 27, 2014
Last verified: June 2014
  Purpose

This study is to find an optimal dose of Imiquimod (IMQ) in the first part (Phase I) and test the effectiveness of the combination treatment of IMQ, cyclophosphamide (CTX), and radiotherapy (RT) in patients with skin metastases from breast cancer in the second part (Phase II). Currently this trial is in its Phase II part.


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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of TLR7 Agonist Imiquimod, Cyclophosphamide, 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 (Complete Response+Partial Response) [ Time Frame: 9 weeks from the strat of the treatment of RT ] [ Designated as safety issue: No ]
    The systemic tumor response refers to the response at the time of best overall response. The response criteria are specially adapted from Response Evaluation Criteria in Solid Tumor for Immunotherapies (ref. 1).


Secondary Outcome Measures:
  • Local tumor response rates (Clinical Complete Response+Partial Response) [ Time Frame: 9 weeks from the start of the treatment ] [ Designated as safety issue: No ]
    The response refers to the best overall response, based on European Organization for Research and Treatment of Cancer's definitions for chest wall tumors (ref. 2).


Estimated Enrollment: 55
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

This arm has been closed as of 6/4/2014.

  • Weeks 1-2: RT given to one metastatic skin site at 6 Gy on days 1, 3, 5, 8 and 10 (M-W-F-M-W)
  • Weeks 1-8: day 1-5 of each week: imiquimod 5% cream applied to all skin sites overnight, starting on day 1 after RT, day 6-7 of each week: rest period.
  • Week 9: response assessment

Patients may continue to receive additional cycles (same schedule, RT given to a different site), provided that patients wish to continue, are without clinically significant progression and further treatment may be beneficial in the opinion of the investigator.

Radiation: Radiation Drug: Imiquimod
Other Name: ALDARA
Experimental: CTX/IMQ/RT
  • Week -1 (day-7): cyclophosphamide 200mg/m2 IV as single infusion
  • Weeks 1-2: RT given to one metastatic skin site at 6 Gy on days 1, 3, 5, 8 and 10 (M-W-F-M-W)
  • Weeks 1-8: day 1-5 of each week: imiquimod 5% cream applied all sites overnight, starting on day 1 after RT, day 6-7 of each week: rest period.
  • Week 9: response assessment

Patients may continue to receive additional cycles (same schedule, RT given to a different site), provided that patients wish to continue, are without clinically significant progression and further treatment may be beneficial in the opinion of the investigator.

Radiation: Radiation Drug: Imiquimod
Other Name: ALDARA
Drug: Cyclophosphamide
Other Name: Cytoxan
Experimental: CTX/RT

For patients with only non-skin metastatic sites

First cycle (Cycle 1):

  • Week -1 (day -7): cyclophosphamide 200mg/m2 IV as single infusion
  • Weeks 1-2: RT given to one site at 6 Gy on days 1, 3, 5, 8 and 10 (M-W-F-M-W)
  • Week 9: response assessment

Patients may continue to receive additional cycles (same schedule, RT given to a different site), provided that patients wish to continue, are without clinically significant progression and further treatment may be beneficial in the opinion of the investigator.

Radiation: Radiation Drug: Cyclophosphamide
Other Name: Cytoxan

Detailed Description:

By harnessing the cytocidal and immunostimulatory properties of two local treatment modalities, RT and IMQ, an effective, adaptive immune response can be generated, resulting in systemic control of metastatic breast cancer after local treatment of cutaneous metastases. Additionally, based on investigators' recent preclinical data, the investigators intend to estimate in patients with metastatic breast cancer, if the addition of immunomodulatory cyclophosphamide can increase anti-tumor responses.

This trial originally had one treatment arm IMQ/RT(patients were treated with IMQ and RT). Recent evidence has emerged that the addition of immunomodulatory cyclophosphamide (CTX) increased anti-tumor responses, therefore the IMQ/RT arm is closed and the trial will continue with two additional cohorts (CTX/IMQ/RT and CTX/RT) which include cyclophosphamide.

  Eligibility

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

Inclusion Criteria:

  1. Patients with biopsy-confirmed breast cancer.
  2. Patients with 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.
  3. Age >= 18 years.
  4. Eastern Cooperative Oncology Group performance status 0-2.
  5. Patients must agree to tumor fine-needle aspiration required by protocol.
  6. Concurrent systemic cancer therapy (hormones, biologics or chemotherapy) can be continued if distant metastases are non-responsive (i.e. no complete response or partial response) 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 if patient has chronic renal insufficiency and creatinine has been stable for > 4 months)
  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 (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.
  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
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: NCT01421017

Contacts
Contact: Sylvia Adams, MD 212-731-5795 sylvia.adams@nyumc.org
Contact: Maria Fenton-Kerimian, NP 212-731-5035 maria.fenton-kerimian@nyumc.org

Locations
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         
Sub-Investigator: Francisco Esteva, MD         
Sub-Investigator: Komal Jhaveri, MD         
Sub-Investigator: Coral Omene, MD         
Sponsors and Collaborators
New York University School of Medicine
Investigators
Principal Investigator: Sylvia Adams, MD New York University School of Medicine
  More Information

Publications:
Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT01421017     History of Changes
Other Study ID Numbers: NYU 11-00598, 1R01CA161891-01
Study First Received: August 17, 2011
Last Updated: June 27, 2014
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Cyclophosphamide
Imiquimod
Adjuvants, Immunologic
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Interferon Inducers
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014