Breast CancerPhase 1/2NCT01421017
Toll-like Receptor (TLR) 7 Agonist, Cyclophosphamide, and Radiotherapy for Breast Cancer With Skin Metastases
A Phase 1/2 study testing Radiation, Imiquimod and Cyclophosphamide in people with Breast Cancer and Metastatic Breast Cancer, run by NYU Langone Health at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, Metastatic Breast Cancer, Recurrent Breast Cancer
- What is being tested?
- Radiation, Imiquimod and Cyclophosphamide
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Aug 2011to 6 Aug 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients with biopsy-confirmed breast cancer.
- Patients with at least 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.
- Age >= 18 years.
- Eastern Cooperative Oncology Group performance status 0-2.
- Patients must agree to tumor fine-needle aspiration required by protocol.
- 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.
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- 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 (aspartate aminotransferase) =< 2.5 X institutional upper limit of normal
- ALT (alanine aminotransferase) =< 2.5 X institutional upper limit of normal
- creatinine =< 2 X institutional upper limit of normal if patient has chronic renal insufficiency and creatinine has been stable for > 4 months)
- Informed consent.
Who cannot join
- Brain metastases unless resected or irradiated and stable >= 4 weeks.
- Concurrent treatment with other investigational agents.
- 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.
- Patients who have received hyperthermia to the target area within 10 weeks prior to first dosing of study agent.
- Patients with an uncontrolled bleeding disorder.
- 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.
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- Patients with known immunodeficiency or receiving immunosuppressive therapies.
- History of allergic reactions to imiquimod or its excipients.
- Uncontrolled intercurrent medical illness or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnancy or lactation.
- Women of childbearing potential not using a medically acceptable means of contraception.
Trial locations and contacts
1 site in 1 country.
United States1 site
New York University Medical Center
New York, New York, 10016
About this study
Official title: Phase I/II Study of TLR7 Agonist Imiquimod, Cyclophosphamide, and Radiotherapy in Breast Cancer Patients With Chest Wall Recurrence or Skin Metastases
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.
Read the 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.
- Being tested
- Radiation, Imiquimod, Cyclophosphamide
- Keywords
- radiation therapy, combination therapy, immunotherapy, immune response modifier, immunostimulatory, immunomodulator
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadiationRadiation
ImiquimodDrug
Also called ALDARA
CyclophosphamideDrug
Also called Cytoxan
| Study group | Role | What they receive |
|---|---|---|
| IMQ+RT | Experimental | 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. Receives: Radiation: Radiation; Drug: Imiquimod |
| CTX/IMQ/RT | Experimental | * 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. Receives: Radiation: Radiation; Drug: Imiquimod; Drug: Cyclophosphamide |
| CTX/RT | Experimental | 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. Receives: Radiation: Radiation; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Systemic Tumor Response Rates (Complete Response+Partial Response)
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).
Measured: 9 weeks from the start of the treatment of RT
Secondary outcomes (1)
Local Skin Tumor Response Rates (Complete Response + Partial Response)
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).
Measured: 9 weeks from the start of the treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2011 (estimated)
- Study start19 Aug 2011
- Primary completion1 Jul 2016
- Study completion6 Aug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe 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
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Sylvia Adams, MD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01421017
- Sponsor's protocol ID
- 11-00598
- Other IDs
- 1R01CA161891-01
- Status last verified
- Oct 2021
- First submitted
- 17 Aug 2011
- Last updated
- 18 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbe C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009 Dec 1;15(23):7412-20. doi: 10.1158/1078-0432.CCR-09-1624. Epub 2009 Nov 24.
PubMed 19934295Kouloulias VE, Dardoufas CE, Kouvaris JR, Gennatas CS, Polyzos AK, Gogas HJ, Sandilos PH, Uzunoglu NK, Malas EG, Vlahos LJ. Liposomal doxorubicin in conjunction with reirradiation and local hyperthermia treatment in recurrent breast cancer: a phase I/II trial. Clin Cancer Res. 2002 Feb;8(2):374-82.
PubMed 11839652Adams S, Demaria S, Rinchai D, Wang E, Novik Y, Oratz R, Fenton-Kerimian M, Levine PG, Li X, Marincola F, Jin P, Stroncek D, Goldberg J, Bedognetti D, Formenti SC. Topical TLR7 agonist and radiotherapy in patients with metastatic breast cancer. J Immunother Cancer. 2025 Apr 5;13(4):e011173. doi: 10.1136/jitc-2024-011173.
PubMed 40187749
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of TLR7 Agonist Imiquimod, Cyclophosphamide, and Radiotherapy in Breast Cancer Patients With Chest Wall Recurrence or Skin Metastases
- ClinicalTrials.gov ID
- NCT01421017
- Acronym / sponsor ID
- 11-00598
- Keywords
- radiation therapy, combination therapy, immunotherapy, immune response modifier, immunostimulatory, immunomodulator
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 19 Aug 2011 (actual)
- Primary completion
- 1 Jul 2016 (actual)
- Study completion
- 6 Aug 2016 (actual)
- First posted
- 22 Aug 2011 (estimated)
- Results
- Posted 18 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| IMQ+RT | Experimental | Radiation: Radiation, Drug: ImiquimodThis 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. |
| CTX/IMQ/RT | Experimental | Radiation: Radiation, Drug: Imiquimod, Drug: Cyclophosphamide* 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. |
| CTX/RT | Experimental | Radiation: Radiation, Drug: CyclophosphamideFor 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients with biopsy-confirmed breast cancer.
- Patients with at least 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.
- Age >= 18 years.
- Eastern Cooperative Oncology Group performance status 0-2.
- Patients must agree to tumor fine-needle aspiration required by protocol.
Key exclusion criteria (11 listed)
- Brain metastases unless resected or irradiated and stable >= 4 weeks.
- Concurrent treatment with other investigational agents.
- 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.
- Patients who have received hyperthermia to the target area within 10 weeks prior to first dosing of study agent.
- Patients with an uncontrolled bleeding disorder.
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 |
|---|---|---|
| Radiation | Radiation | CTX/IMQ/RT, CTX/RT, IMQ+RT |
| ImiquimodAlso: ALDARA | Drug | CTX/IMQ/RT, IMQ+RT |
| CyclophosphamideAlso: Cytoxan | Drug | CTX/IMQ/RT, CTX/RT |
Primary outcome
Systemic Tumor Response Rates (Complete Response+Partial Response)
Time frame: 9 weeks from the start of the treatment of RT
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).
1 secondary outcome
Local Skin Tumor Response Rates (Complete Response + Partial Response)
Time frame: 9 weeks from the start of the treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19934295Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbe C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009 Dec 1;15(23):7412-20. doi: 10.1158/1078-0432.CCR-09-1624. Epub 2009 Nov 24.
- Background: PubMed 11839652Kouloulias VE, Dardoufas CE, Kouvaris JR, Gennatas CS, Polyzos AK, Gogas HJ, Sandilos PH, Uzunoglu NK, Malas EG, Vlahos LJ. Liposomal doxorubicin in conjunction with reirradiation and local hyperthermia treatment in recurrent breast cancer: a phase I/II trial. Clin Cancer Res. 2002 Feb;8(2):374-82.
- Derived from this study: PubMed 40187749Adams S, Demaria S, Rinchai D, Wang E, Novik Y, Oratz R, Fenton-Kerimian M, Levine PG, Li X, Marincola F, Jin P, Stroncek D, Goldberg J, Bedognetti D, Formenti SC. Topical TLR7 agonist and radiotherapy in patients with metastatic breast cancer. J Immunother Cancer. 2025 Apr 5;13(4):e011173. doi: 10.1136/jitc-2024-011173.
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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.
Sylvia Adams, MD principal investigator
NYU Langone Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Radiation, Imiquimod and Cyclophosphamide in people with Breast Cancer and Metastatic Breast Cancer, run by NYU Langone Health at 1 site in United States.
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 15 inclusion and 11 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: finished, as of the sponsor's last update on 18 Nov 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 United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Systemic Tumor Response Rates (Complete Response+Partial Response) (time frame: 9 weeks from the start of the treatment of RT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01421017, which also lists 3 linked publications.
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 18 Nov 2021.