RadiotherapyEarly Phase 1NCT02441270
Evaluation of the Immunological Effects of a Combined Treatment With Radiation and Cyclophosphamide in Metastasized Breast Cancer Patients
A Early Phase 1 study testing Cyclophosphamide and Stereotactic body radiotherapy in people with Radiotherapy and Immunology, run by University Hospital, Ghent at 1 site in Belgium.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Radiotherapy, Immunology
- What is being tested?
- Cyclophosphamide and Stereotactic body radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteBelgium
- Study dates
- Apr 2015to 15 May 2018
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
- Conditions
- Radiotherapy, Immunology
- Being tested
- Cyclophosphamide, Stereotactic body radiotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Stereotactic body radiotherapyRadiation
| Study group | Role | What they receive |
|---|---|---|
| Cyclophosphamide | Experimental | Not described Receives: Drug: Cyclophosphamide; Radiation: Stereotactic body radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of the immunological effects, in peripheral blood and tumor biopsies, of the combined treatment with radiation and cyclophosphamide
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.
Immune monitoring:
Before the first session of radiation, 4 weeks after radiotherapy and 3 months after radiotherapy.
Measured: 1.5 years
Secondary outcomes (2)
Evaluation of the clinical/radiographical response of irradiated metastases
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.
Measured: 1.5 years
Evaluation of the response of non-irradiated metastases (the so-called "abscopal effect").
Evaluation of the "abscopal effect" will be done by using the RECIST criteria and the immune related response criteria (irRC) 3 months post-radiotherapy.
Measured: 1.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2015 (estimated)
- Study startApr 2015
- Primary completion15 May 2018
- Study completion15 May 2018
Why it stopped: Study was never started.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RadiotherapyStudies of the same condition, open and under way.
- More trials run by University Hospital, GhentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Ghent
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02441270
- Sponsor's protocol ID
- EC 2015/0204
- Status last verified
- Jul 2021
- First submitted
- 24 Apr 2015
- Last updated
- 13 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Immunological Effects of a Combined Treatment With Radiation and Cyclophosphamide in Metastasized Breast Cancer Patients
- ClinicalTrials.gov ID
- NCT02441270
- Acronym / sponsor ID
- EC 2015/0204
- Conditions
- Radiotherapy, Immunology
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study was never started.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Hospital, GhentUniversity, hospital or other
- Study start
- Apr 2015
- Primary completion
- 15 May 2018 (actual)
- Study completion
- 15 May 2018 (actual)
- First posted
- 12 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cyclophosphamide | Experimental | Drug: Cyclophosphamide, Radiation: Stereotactic body radiotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cyclophosphamide | Drug | Cyclophosphamide |
| Stereotactic body radiotherapy | Radiation | Cyclophosphamide |
Primary outcome
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. Immune monitoring: Before the first session of radiation, 4 weeks after radiotherapy and 3 months after radiotherapy.
2 secondary outcomes
Evaluation of the clinical/radiographical response of irradiated metastases
Time frame: 1.5 years
Evaluation of the response of non-irradiated metastases (the so-called "abscopal effect").
Time frame: 1.5 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Cyclophosphamide and Stereotactic body radiotherapy in people with Radiotherapy and Immunology, run by University Hospital, Ghent at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 13 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of the immunological effects, in peripheral blood and tumor biopsies, of the combined treatment with radiation and cyclophosphamide (time frame: 1.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2021.