Toll-like Receptor (TLR) 7 Agonist and Radiotherapy for Breast Cancer With Skin Metastases
The cell killing and immunostimulatory properties of two local treatment modalities, radiotherapy (RT) and Imiquimod (IMQ), may generate an effective immune response and lead to systemic control of breast cancer after local treatment of the cancer on the skin spread from the breast (skin metastases). This study is to find an optimal dose of IMQ in the first part and test the effectiveness of the combination treatment of RT and IMQ in patients with skin metastases from breast cancer in the second part.
Metastatic Breast Cancer
Recurrent Breast Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of TLR7 Agonist Imiquimod and Radiotherapy in Breast Cancer Patients With Chest Wall Recurrence or Skin Metastases|
- systemic tumor response rates (CR+PR) at the time of best overall response (Ph II) [ Time Frame: 9 weeks from the strat of the treatment ] [ Designated as safety issue: No ]
- local tumor response rates (CCR+PR) at best overall response (Ph II) [ Time Frame: 9 weeks from the start of the treatment ] [ Designated as safety issue: No ]
|Study Start Date:||August 2011|
|Estimated Study Completion Date:||February 2016|
|Estimated Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
At trial entry, all skin metastases will be divided into two areas (A) and (B) for differential treatment. Area A will receive IMQ + RT while area B will only receive IMQ. The size and location of cutaneous metastases for RT (area A) will be chosen by the radiation oncologist, to assure avoidance of overtreatment by radiation in pre-irradiated patients. All cutaneous metastases outside of area A will be included in area B.
Radiotherapy will be administered to Area A at a dose of 6 Gy given at five fractions on days 1, 3, 5, 8 and 10 (M-W-F-M-W) during a 8-week treatment cycle. All patients may continue to receive additional cycles (same schedule, RT given to a different cutaneous area, which may comprise all the prior area B), provided that patients wish to continue, are without clinically significant progression and further treatment may be beneficial in the opinion of the investigatorDrug: Imiquimod
Treatment with topical imiquimod 5% to all skin metastases (Areas A and B) starts the evening after the first radiation dose (day 1). IMQ treatment is given 5 days/week or Days 1, 3, 5/week for a total of 8 weeks (=1 cycle). The treatment dose is determined by tumor area: One single-use packet of imiquimod 5% (250 mg cream) per day is used for tumors <100cm^2, an additional package/d is added for each additional 100cm^2 area, not to exceed 6 packets/d. Patients self-apply a thin layer of IMQ 5% topically in the evening and wash it off the next morning (6-10 hours after initial application) with mild soap and water to remove any residual cream.
Other Name: ALDARA
This is a single arm, open label Phase I/II clinical trial to treat breast cancer with skin metastases (chest wall or other sites).
A brief Phase I part is conducted, to allow dose optimization in the event of unanticipated adverse events (3-3 design). In the Phase II part, efficacy is the primary endpoint. Twenty five patients will be enrolled to Phase II.
|Contact: Sylvia Adams, MDemail@example.com|
|Contact: Maria Fenton-Kerimian, NPfirstname.lastname@example.org|
|United States, New York|
|New York University Medical Center||Recruiting|
|New York, New York, United States, 10016|
|Principal Investigator: Silvia Formenti, MD|
|Sub-Investigator: Yelena Novik, MD|
|Sub-Investigator: James Speyer, MD|
|Sub-Investigator: Franco Muggia, MD|
|Sub-Investigator: Ruth Oratz, MD|
|Sub-Investigator: Nelly Huppert, MD|
|Principal Investigator: Sylvia Adams, MD|
|Principal Investigator:||Sylvia Adams, MD||New York University School of Medicine|