Evaluation of the Immunological Effects of a Combined Treatment With Radiation and Cyclophosphamide in Metastasized Breast Cancer Patients

Ghent University Hospital (UZ)

Status and phase

Withdrawn

Early Phase 1

Conditions

Immunology

Radiotherapy

Treatments

Drug: Cyclophosphamide

Radiation: Stereotactic body radiotherapy

Study type

Interventional

Funder types

Other

Identifiers

NCT02441270

EC 2015/0204

Details and patient eligibility

About

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.

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically proven diagnosis of breast cancer
Evidence of metastasized disease on imaging or during clinical examination
Progressive disease during last systemic treatment
Multiple (≥2) measurable lesions accessible for repeat biopsy, in particular:
Skin- or subcutaneous metastases
Lymph node metastases cervical, supraclavicular, axillary or inguinal
Superficial lesions in the breast or on the thoracic wall
Age ≥ 18 years
Adequate organ and bone marrow function:
ANC > 1500/µL
haemoglobin > 9 g/dL (potentially after transfusion)
thrombocytes ≥ 100 000/µL
total bilirubin ≤ 1.5 X maximum reference value
AST ≤ 2.5 X maximum reference value
ALT ≤ 2.5 X maximum reference value
creatinin ≤ 1.5 X maximum reference value
Informed consent
Chemotherapy or targeted therapy should be stopped for at least 1 month before the start of cyclophosphamide. Hormone therapy can be continued if it was not changed in the last 3 months

Exclusion criteria

Life expectancy of less than 3 months or Karnofsky performance status < 70
New line of systemic therapy planned
Concomitant treatment with other experimental drugs
Local therapies (radiation, surgery, topical anti-cancer treatment, intralesional therapy, laser treatment) at the target lesion(s) less than 4 weeks before the start of cyclophosphamide. Biopsy is allowed.
Chemotherapy or targeted therapy < 4 weeks before the start of cyclophosphamide
Hormone therapy change within the last 3 months
Uncontrolled coagulation disorders
Patients receiving therapeutic anticoagulants that cannot be stopped temporarily for repeat biopsy. Aspirin or anti-aggregants are allowed.
Patients with a known immune-deficiency disorder or receiving immune-suppressive treatment
Known allergy or intolerance for cyclophosphamide
Pregnant or breastfeeding
Women in the reproductive age not using a medically accepted method of contraception
Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study
Patient unlikely to comply with the protocol; i.e. uncooperative attitude, inability to return for follow-up visits, and unlikely to complete the study