Breast Cancer Study of Preoperative Pembrolizumab + Radiation
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03366844|
Recruitment Status : Recruiting
First Posted : December 8, 2017
Last Update Posted : March 6, 2020
This study is being done to assess the feasibility of pembrolizumab (study drug) combined with standard radiation to the tumor (tumor boost) before patients undergo standard treatment that can consist of one or more of the following: breast-conserving surgery, radiation to the entire breast/chest wall after surgery, and chemotherapy.
Study participants will receive two doses of the study drug intravenously (through the vein) before their planned breast surgery or chemotherapy. The study drug will be administered three weeks apart. At the time of the second dose, radiation to the tumor in the affected breast will be given. This type of radiation treatment is called a "tumor boost", which is a standard part of radiation therapy for breast cancer that may occur either before or after planned breast-conserving surgery. Patients will receive breast surgery or begin chemotherapy approximately six weeks after your first dose of the study drug.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: Pembrolizumab Radiation: RT Boost||Phase 1 Phase 2|
With more than 1 million new cases diagnosed yearly worldwide, breast cancer is a global public health burden. Over the past decade, molecular subtyping of breast cancer has identified intrinsic subtypes that may be at enhanced risk for both local and distant recurrence. This study focuses on the immunogenicity of high-risk breast cancer subtypes that are likely to display a dense lymphocytic infiltration including including TNBC and HR+/HER2- tumors.
Immune build up via immune co-stimulatory molecules permits the ensuing immune response to strengthen and destroy cancer systemically. Thus, the effect of the anti-tumor immune response initiated by the radiation to an intact tumor by combination with checkpoint blockade is increased.
Pembrolizumab is an optimal immunotherapy agent to study, as this agent has recently been FDA approved for use in multiple tumor types. It is therefore ready to be tested for efficacy in other disease sites and in combination with other treatments.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||
Single Arm with Two Cohorts
|Masking:||None (Open Label)|
|Official Title:||Preoperative Combination of Pembrolizumab and Radiation Therapy in Patients With Operable Breast Cancer|
|Actual Study Start Date :||December 22, 2017|
|Estimated Primary Completion Date :||January 1, 2021|
|Estimated Study Completion Date :||January 1, 2021|
Experimental: Pembrolizumab with RT Boost
Study drug plus "tumor boost" before standard of care treatment
Radiation: RT Boost
The second dose of pembrolizumab will be given in conjunction with an RT boost, consisting of 8 Gy for 3 fractions.
- Number of patients who do not necessitate a delay in standard of care treatment after receiving the investigational combination of preoperative Pembrolizumab and radiation [ Time Frame: 8 weeks after trial initiation ]Feasibility of preoperative radiation and Pembrolizumab in newly diagnosed, non-metastatic patients with triple negative breast cancer.
- Changes in Tumor Infiltrating Lymphocytes (TIL) [ Time Frame: 8 weeks after trial initiation ]An increase in the tumor-infiltrating lymphocyte score as measured by Salgado criteria
- Pembrolizumab-related adverse events [ Time Frame: 15 weeks after trial initiation ]Treatment toxicities
- Immune-related adverse events [ Time Frame: One year post treatment ]Treatment toxicities
- Invasive disease-free survival after preoperative radiation and Pembrolizumab [ Time Frame: From treatment start date until date of documented recurrence or death from breast cancer, assessed up to 19 weeks after start of treatment ]Disease-free survival, as described from time from occurrence of surgery to time from first recurrence from or death from breast cancer
- Pathological complete response rate [ Time Frame: From treatment start date until the time of curative-intent surgery, approximately 8 weeks. ]Absence of invasive disease in the breast and lymph nodes at the time of curative-intent surgery.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03366844
|Contact: Cindi Martin||310-423-2276||Cynthia.Martin@cshs.org|
|United States, California|
|Cedars-Sinai Medical Center||Recruiting|
|Los Angeles, California, United States, 90048|
|Contact: Cindi Martin 310-423-2276 Cynthia.Martin@cshs.org|
|Sub-Investigator: Monica Mita, MD|
|Sub-Investigator: Reva Basho, MD|
|Sub-Investigator: Heather McArthur, MD|
|Sub-Investigator: Stephen Shiao, MD|
|Sub-Investigator: Armando Giuliano, MD|
|Sub-Investigator: Amin Mirhadi, MD|
|Sub-Investigator: Mitchell Kamrava, MD|
|Sub-Investigator: Michele Burnison, MD|
|Sub-Investigator: Farin Amersi, MD|
|Sub-Investigator: Catherine Dang, MD|
|Sub-Investigator: Scott Karlan, MD|
|Sub-Investigator: Alice Chung, MD|
|Sub-Investigator: Dorothy Park, MD|
|Sub-Investigator: Michael Van Scoy-Moser, MD|
|Sub-Investigator: Philomena McAndrew, MD|
|Sub-Investigator: Maryliza El-Masry, MD|
|Sub-Investigator: Nimmi Kapoor, MD|
|Sub-Investigator: Farnaz Dadmanesh, MD|
|Sub-Investigator: Xuemo Fan, MD|
|Principal Investigator:||Stephen Shiao, MD, PHD||Cedars-Sinai Medical Center|