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

NCT ID: NCT01421017

Last Updated: 2021-11-18

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

31 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-08-19

Study Completion Date

2016-08-06

Brief Summary

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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

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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.

Conditions

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Breast Cancer Metastatic Breast Cancer Recurrent Breast Cancer

Keywords

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radiation therapy combination therapy immunotherapy immune response modifier immunostimulatory immunomodulator

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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IMQ+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.

Group Type EXPERIMENTAL

Radiation

Intervention Type RADIATION

Imiquimod

Intervention Type DRUG

CTX/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.

Group Type EXPERIMENTAL

Radiation

Intervention Type RADIATION

Imiquimod

Intervention Type DRUG

Cyclophosphamide

Intervention Type DRUG

CTX/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.

Group Type EXPERIMENTAL

Radiation

Intervention Type RADIATION

Cyclophosphamide

Intervention Type DRUG

Interventions

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Radiation

Intervention Type RADIATION

Imiquimod

Intervention Type DRUG

Cyclophosphamide

Intervention Type DRUG

Other Intervention Names

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ALDARA Cytoxan

Eligibility Criteria

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Inclusion Criteria

1. Patients with biopsy-confirmed breast cancer.
2. 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.
3. Age \>= 18 years.
4. Eastern Cooperative Oncology Group performance status 0-2.
5. Patients must agree to tumor fine-needle aspiration required by protocol.
6. 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.
7. 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)
8. Informed consent.

Exclusion Criteria

1. Brain metastases unless resected or irradiated and stable \>= 4 weeks.
2. Concurrent treatment with other investigational agents.
3. 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.
4. Patients who have received hyperthermia to the target area within 10 weeks prior to first dosing of study agent.
5. Patients with an uncontrolled bleeding disorder.
6. 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.
7. Patients with known immunodeficiency or receiving immunosuppressive therapies.
8. History of allergic reactions to imiquimod or its excipients.
9. Uncontrolled intercurrent medical illness or psychiatric illness/social situations that would limit compliance with study requirements.
10. Pregnancy or lactation.
11. Women of childbearing potential not using a medically acceptable means of contraception.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

NYU Langone Health

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sylvia Adams, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Locations

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New York University Medical Center

New York, New York, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 19934295 (View on PubMed)

Kouloulias 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.

Reference Type BACKGROUND
PMID: 11839652 (View on PubMed)

Adams 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.

Reference Type DERIVED
PMID: 40187749 (View on PubMed)

Other Identifiers

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1R01CA161891-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

11-00598

Identifier Type: -

Identifier Source: org_study_id