Evaluation of the Immunological Effects of a Combined Treatment With Radiation and Cyclophosphamide in Metastasized Breast Cancer Patients
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|ClinicalTrials.gov Identifier: NCT02441270|
Recruitment Status : Unknown
Verified May 2015 by University Hospital, Ghent.
Recruitment status was: Recruiting
First Posted : May 12, 2015
Last Update Posted : May 12, 2015
In metastasized of locally advanced breast cancer patients, local problems often occur like skin metastases, ulcerations or lymph node metastases. These problems are related to a worse quality of life, while overall survival is generally in the order of months to years. Treatment of these lesions is challenging, especially after failure of first or second line systemic therapy. Local treatments, like radiation, are able to give short-term palliation, but the effect is often disappointing in the long run. Therefore, the search for new therapeutic strategies like the combination of local and systemic treatments is emerging.
Recent investigations clearly show that radiation is capable of inducing a systemic anti-tumor response. Both in mouse models and in patients, it was reported that irradiating one metastasis can slow down the growth of other non-irradiated metastases. This effect is called the "abscopal effect" and is immune-mediated. There are also several chemotherapeutics that are capable of influencing the immune response like cyclophosphamide. Cyclophosphamide is a known inducer of immunogenic cell death, which leads to the activation of dendritic cells and thus the presentation of antigens.
In this pilot study the investigators wish to identify the immunological effects of combined treatment with radiation and cyclophosphamide in breast cancer patients. Five patients with metastasized breast carcinoma will be treated with the combined treatment and the immunological effects will be monitored using repeat blood draws and biopsies. These effects will be correlated to the clinical response.
|Condition or disease||Intervention/treatment||Phase|
|Radiotherapy Immunology||Drug: Cyclophosphamide Radiation: Stereotactic body radiotherapy||Early Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Evaluation of the Immunological Effects of a Combined Treatment With Radiation and Cyclophosphamide in Metastasized Breast Cancer Patients|
|Study Start Date :||April 2015|
|Estimated Primary Completion Date :||October 2016|
Radiation: Stereotactic body radiotherapy
- Identification of the immunological effects, in peripheral blood and tumor biopsies, of the combined treatment with radiation and cyclophosphamide [ Time Frame: 1.5 years ]
Biopsies will be divided for 1) flowcytometric analysis (CD4 and CD8 tumor infiltrating lymphocytes, Tregs, dendritic cell subsets) and 2) immune histochemistry (CD8 tumor infiltrating lymphocytes, Foxp3+ Tregs).
Immunomonitoring in peripheral blood by flow-cytometric analysis of leukocyte subsets involved in tumor-related immune responses: NK and T-cell subsets, dendritic cell subsets and myeloid-derived suppressor cells. Cytokine secretion patterns will be investigated using FACS and ELISA.
Before the first session of radiation, 4 weeks after radiotherapy and 3 months after radiotherapy.
- Evaluation of the clinical/radiographical response of irradiated metastases [ Time Frame: 1.5 years ]
Evaluation of the clinical response of irradiated metastases will be done by monthly photographic documentation of all skin lesions.
Evaluation of the radiographical response of irradiated metastases by 3-monthly imaging.
- Evaluation of the response of non-irradiated metastases (the so-called "abscopal effect"). [ Time Frame: 1.5 years ]Evaluation of the "abscopal effect" will be done by using the RECIST criteria and the immune related response criteria (irRC) 3 months post-radiotherapy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02441270
|University Hospital - Radiotherapy Department||Recruiting|
|Ghent, Belgium, 9000|
|Contact: Liv Veldeman, MD, PhD email@example.com|
|Principal Investigator: Liv Veldeman, MD, PhD|
|Sub-Investigator: Katrien De Wolf, MD|