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

NCT01421017 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 11-005981R01CA161891-01
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief 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). Currently this trial is in its Phase II part.

Conditions

Breast Cancer; Metastatic Breast Cancer; Recurrent Breast Cancer

Keywords

radiation therapy; combination therapy; immunotherapy; immune response modifier; immunostimulatory; immunomodulator

Outcome Measures

Primary Outcomes (1)

• 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).

  9 weeks from the start of the treatment of RT

Secondary Outcomes (1)

• Local Skin Tumor Response Rates (Complete Response + Partial Response)

  9 weeks from the start of the treatment

Study Arms (3)

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.

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.

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.

Radiation: Radiation; Drug: Cyclophosphamide

Interventions

Radiation RADIATION

CTX/IMQ/RT; CTX/RT; IMQ+RT

Imiquimod DRUG

Also known as: ALDARA

CTX/IMQ/RT; IMQ+RT

Cyclophosphamide DRUG

Also known as: Cytoxan

CTX/IMQ/RT; CTX/RT

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• NYU Langone Health: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

New York University Medical Center

New York, New York, 10016, United States

Location

Related Publications (3)

• 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.

  PMID: 19934295 BACKGROUND

• 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.

  PMID: 11839652 BACKGROUND

• 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.

  PMID: 40187749 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Radiation; Imiquimod; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Sylvia Adams
• Organization: NYU Langone Health

sylvia.adams@nyumc.org

212-731-5795

Study Officials

• Sylvia Adams, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2011
• First Posted: August 22, 2011
• Study Start: August 19, 2011
• Primary Completion: July 1, 2016
• Study Completion: August 6, 2016
• Last Updated: November 18, 2021
• Results First Posted: November 18, 2021

Record last verified: 2021-10

Locations

US (1)