Breast Cancer, Breast Neoplasms
Conditions
Keywords
toll-like receptor, toll-like receptor agonist, recurrent breast cancer, breast cancer metastasized to skin and/or chestwall, immunomodulator
Brief summary
The purpose of this trial is to determine the safety and efficacy of Imiquimod, a Toll-like receptor 7 agonist in breast cancer (for chestwall recurrences or metastases to the skin).
Detailed description
TLR agonists are novel agents for cancer therapy which modify the immune response. Imiquimod, a synthetic TLR7 agonist has proven immunomodulatory activity when applied topically, leading to clearance of human papilloma virus (HPV)-induced genital warts and primary skin malignancies. Its effects will now be examined in breast cancer metastatic to the skin. If effective, it will add a relatively non-toxic approach to the treatment armamentarium for this patient population frequently resistant to conventional therapies.
Interventions
DRUGImiquimod
Each treatment cycle consists of 8 weeks. Weeks 1-8: day 1-5 of each week: 1 packet imiquimod 5% cream applied overnight, day 6-7 of each week: rest period. Patients with responding or stable local disease (non-progressors) may continue to receive treatment following the same schedule (as outlined above for the first cycle) until complete tumor regression, unacceptable toxicity or progression of disease.
Sponsors
NYU Langone Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with biopsy-confirmed breast cancer (prior histological documentation is acceptable). * Patients with measurable skin metastases (chest wall recurrence and/or non-chest wall skin metastases are eligible). * Skin metastases not suitable for or patient refusing definitive surgical resection and radiation. * (Cohort 1) Concurrent systemic cancer therapy (hormones, biologics or chemotherapy) is allowed if distant metastases have been non-progressing (stable or responding) on that regimen for \> or = 12 weeks and skin metastases are non-responsive (stable or progressing) as assessed by the investigator. (Cohort 2) Any concurrent systemic therapy is allowed * Age at least 18 years. * Eastern Cooperative Oncology Group (ECOG) performance status \< or = 2. * Patients must have biopsy-accessible tumor (skin metastases) and agree to biopsies required by protocol. * Patients must have adequate organ and bone marrow function as defined below: * absolute neutrophil count \> or = 1,500/microliter * hemoglobin \> or = 9.5 grams/deciliter * platelets \>or = 75,000/microliter * total bilirubin \< or = 1.5 X institutional upper limit of normal * Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) \< or = 2.5X institutional upper limit of normal * creatinine \< or = 1.5 X institutional upper limit of normal * Informed consent.
Exclusion criteria
* Brain metastases unless resected or irradiated and stable \> or = 8 weeks. * Treatment with other investigational agents. * Patients who have received 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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response (Complete Clinical Response+ Partial Response) | 9 weeks | This is defined as percentage of patients who achieved complete clinical response or partial response at end of cycle 1 of treatment. The tumor size will be measured as lesion surface area (region of interest, ROI). The response to the treatment is then evaluated as a function of post-treatment over pre-treatment ROI, expressed in percentage. Response criteria for this study are based on European Organisation for Research and Treatment of Cancer definitions for chest wall tumors: complete clinical response: absence of any detectable residual disease; partial response: \<50% of ROI change. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefits | 9 weeks | This outcome measure is defined as number of patients with improvement of symptoms after 8 weeks of treatment. |
Countries
United States
Participant flow
Recruitment details
Ten patients were enrolled to this study between Nov. 2009 and Nov. 2010 at New York University Medical Center and affiliated hospital.
Participants by arm
| Arm | Count |
|---|---|
| Imiquimod Each treatment cycle consists of 8 weeks.
Weeks 1-8: day 1-5 of each week: 1 packet imiquimod 5% cream applied overnight, day 6-7 of each week: rest period.
Patients with responding or stable local disease (non-progressors) may continue to receive treatment following the same schedule (as outlined above for the first cycle) until complete tumor regression, unacceptable toxicity or progression of disease. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Imiquimod |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 50 years |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Objective Response (Complete Clinical Response+ Partial Response)
This is defined as percentage of patients who achieved complete clinical response or partial response at end of cycle 1 of treatment. The tumor size will be measured as lesion surface area (region of interest, ROI). The response to the treatment is then evaluated as a function of post-treatment over pre-treatment ROI, expressed in percentage. Response criteria for this study are based on European Organisation for Research and Treatment of Cancer definitions for chest wall tumors: complete clinical response: absence of any detectable residual disease; partial response: \<50% of ROI change.
Time frame: 9 weeks
Population: Patients who completed 1 cycle of treatment (8 weeks) and response evaluation at week 9.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imiquimod | Objective Response (Complete Clinical Response+ Partial Response) | 20 percentage of patients |
Secondary
Clinical Benefits
This outcome measure is defined as number of patients with improvement of symptoms after 8 weeks of treatment.
Time frame: 9 weeks
Population: Patients who completed 1 cycle of treatment (8 weeks) and response evaluation at week 9.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Imiquimod | Clinical Benefits | Pain improvement | 4 patients |
| Imiquimod | Clinical Benefits | Pruritus improvement | 5 patients |
| Imiquimod | Clinical Benefits | Dermatology Life Quality Index (DLQI) improvement | 0 patients |