Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Recurrence

Breast Neoplasms

Neoplasm Metastasis

Breast Diseases

Skin Diseases

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Cyclophosphamide

Immunomodulating Agents

Imiquimod

Adjuvants, Immunologic

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Interferons

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.

* 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.

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

Sylvia Adams, MD

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.

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.

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

Phase I/II Study of TLR7 Agonist Imiquimod, Cyclophosphamide, and Radiotherapy in Breast Cancer Patients With Chest Wall Recurrence or Skin Metastases

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 (Wolchok, et al., 2009).

The response refers to the best overall response, based on European Organization for Research and Treatment of Cancer's definitions for chest wall tumors (Kouloulias, et al., 2002).

National Cancer Institute (NCI)

NYU Langone Health

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 Imiquimod

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 Imiquimod Cyclophosphamide

CTX/IMQ/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 Cyclophosphamide

CTX/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

Imiquimod

* 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

Imiquimod

Cyclophosphamide

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

Cyclophosphamide

Total

Mean Age

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Sylvia Adams

Systemic Tumor Response Rates (Complete Response+Partial Response)

Local Area A; irradiated area

Local Area B; non-irradiated area

Arm "CTX/RT" is not applicable, as it includes only patients with non-skin metastatic sites.

Local Skin Tumor Response Rates (Complete Response + Partial Response)

Overall Study

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Neuroendocrine Tumor

Neuroepithelioma

Patients with metastatic melanoma will be given 0.4 mg/kg anti-OX40 on days 1, 3 and 5 of a single treatment cycle.

anti-OX40

Brendan D Curti, MD

In this study, anti-OX40 will be given to patients with melanoma to find out how the immune system responds to treatment with anti-OX40. It is hoped that this treatment will cause an immune response against melanoma resulting in tumor regression, but this is not known at this time. Anti-OX40 is a large protein that can help immune cells that fight bacteria, viruses and cancer cells.

Study of Immune Responses in Patients With Metastatic Melanoma

Phase II Exploratory Study of Immune Responses in Patients With Metastatic Melanoma Treated With Mouse Monoclonal Anti-OX40

T Cells will be harvested by apheresis at baseline and Day 15 following anti-OX40 administration.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Toll-like Receptor (TLR) 7 Agonist, Cyclophosphamide, and Radiotherapy for Breast Cancer With Skin Metastases	NCT01421017	Breast Cancer Metastatic Brea... Recurrent Breas...	Radiation Imiquimod Cyclophosphamid...	18 Years -	NYU Langone Health
Study of Immune Responses in Patients With Metastatic Melanoma	NCT01416844	Metastatic Mela...	anti-OX40	18 Years -	Providence Health & Services
Study of Immune Responses in Patients With Metastatic Melanoma	NCT01416844	Metastatic Mela...	anti-OX40	18 Years -	Providence Health & Services

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