- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04454528
BreastVAX: Radiation Boost to Enhance Immune Checkpoint Blockade Therapy (BreastVAX)
Preoperative Use of Radiation Boost to Enhance Effectiveness of Immune Checkpoint Blockade Therapy in Operable Breast Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Julia C Tchou, MD
- Phone Number: 215-615-7575
- Email: Julia.tchou@pennmedicine.upenn.edu
Study Contact Backup
- Name: Michelle Gelman
- Phone Number: 215-882-2702
- Email: michelle_gelman@pennmedicine.upenn.edu
Study Locations
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104
- Recruiting
- Perelman Center for Advanced Medicine
-
Contact:
- Julia Tchou, MD, PhD
- Phone Number: 800-789-7366
-
Contact:
- Carolina Reyes, BS
- Phone Number: 6093153901
- Email: Carolina.Reyes1@Pennmedicine.upenn.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Men and women age ≥ 18 years old (unless otherwise specified) Willing and able to provide written informed consent/assent ECOG Performance Status 0 - 1
Patients with:
Newly diagnosed breast cancer with tumor size < 5 cm who are not eligible for I-SPY2 (to prevent recruitment competition), or not recommended to undergo standard of care neoadjuvant chemotherapy with at least one of the following features:
- Triple negative breast cancer (TNBC) defined using the ASCO CAP guidelines with the following modification supported by a recent publication as ER ≤ 10%, PR ≤ 10%, HER2- determined by immunohistochemistry and/or fluorescence in situ hybridization analyses and with tumor size ≤ 2.5 cm;
- HR+ HER2- breast cancer regardless of nodal status and age of diagnosis ≥ 50
- HR+ HER2- breast cancer and age of diagnosis <50 with tumor size ≤ 2.5 cm and clinically node (+)
- HR+ or HR- and HER2+ breast cancer with tumor size ≤ 2.5 cm
- Ductal carcinoma in situ (DCIS) with microinvasion
OR
- Locally recurrent breast cancer of any receptor subtype with no prior radiation, not recommended to receive neoadjuvant chemotherapy and expecting surgical excision as part of treatment.
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 of the study protocol OR
A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during the treatment period and for at least 120 days for study treatments with risk of genotoxicity after the last dose of study treatment.
- Female participants of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Medically accepted methods of birth control include a diaphragm, cervical cap, latex condoms, surgical sterility, intrauterine devices (IUDs), hormonal implants, injectable contraceptives, or birth control pills. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Ability to tolerate radiation therapy (e.g., lie flat and hold position)
- Demonstrate adequate hematologic, renal, hepatic, thyroid, and bone marrow function
Inclusion Criteria:
- Men and women age ≥ 18 years old (unless otherwise specified)
- Willing and able to provide written informed consent/assent
- ECOG Performance Status 0 - 1
Patients with:
Newly diagnosed breast cancer with tumor size < 5 cm who are not eligible for I-SPY2 (to prevent recruitment competition), or not recommended to undergo standard of care neoadjuvant chemotherapy with at least one of the following features:
- Triple negative breast cancer (TNBC) defined using the ASCO CAP guidelines with the following modification supported by a recent publication as ER ≤ 10%, PR ≤ 10%, HER2- determined by immunohistochemistry and/or fluorescence in situ hybridization analyses and with tumor size ≤ 2.5 cm;
- HR+ HER2- breast cancer regardless of nodal status and age of diagnosis ≥ 50
- HR+ HER2- breast cancer and age of diagnosis <50 with tumor size ≤ 2.5 cm and clinically node (+)
- HR+ or HR- and HER2+ breast cancer with tumor size ≤ 2.5 cm
- Ductal carcinoma in situ (DCIS) with microinvasion
OR
Locally recurrent breast cancer of any receptor subtype with no prior radiation, not recommended to receive neoadjuvant chemotherapy and expecting surgical excision as part of treatment.
• A female participant is eligible to participate if she is not pregnant (see Appendix 2), not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in Appendix 2. OR
A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during the treatment period and for at least 120 days for study treatments with risk of genotoxicity after the last dose of study treatment.
• Female participants of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Medically accepted methods of birth control include a diaphragm, cervical cap, latex condoms, surgical sterility, intrauterine devices (IUDs), hormonal implants, injectable contraceptives, or birth control pills. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Ability to tolerate radiation therapy (e.g., lie flat and hold position)
- Demonstrate adequate hematologic, renal, hepatic, thyroid, and bone marrow function
Exclusion criteria:
• A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• A history of prior radiotherapy to the ipsilateral breast/chest wall that precludes delivery of hypofractionated radiotherapy.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks
• Has not adequately recovered from major surgery or has ongoing surgical complications
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid)
• Participants with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Participants that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Participants with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study. Steroid prep due to dye allergies prior to staging scans or use in anti-emetic prophylaxis is allowed.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
Note: please refer to Section 5.7 for information on COVID-19 vaccines • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has had an allogenic tissue/solid organ transplant.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Arm 1
Arm 1 will receive radiotherapy on day -14 and pembrolizumab on day -7.
Subjects in all arms will undergo surgery on day 0 and follow the same postoperative blood sampling and safety schedule.
|
Radiation boost (RT) 7 Gy x 1 fraction on Day -14/Day -7 (arm 1) or Day -7/Day -14
Other Names:
Pembrolizumab infusion flat dosing 200 mg delivered over 30 minutes.
Other Names:
Blood will be collected for laboratory studies and complete correlative studies to examine how the subject's immune system is responding to treatment.
On day 0, samples of tumor and any lymph nodes removed from armpit will be analyzed by the UPenn Department of Pathology according to standard practice.
Other Names:
|
Active Comparator: Arm 2
Arm 2 will receive pembrolizumab on day -14 and radiotherapy on day -7.
Subjects in all arms will undergo surgery on day 0 and follow the same postoperative blood sampling and safety schedule.
|
Radiation boost (RT) 7 Gy x 1 fraction on Day -14/Day -7 (arm 1) or Day -7/Day -14
Other Names:
Pembrolizumab infusion flat dosing 200 mg delivered over 30 minutes.
Other Names:
Blood will be collected for laboratory studies and complete correlative studies to examine how the subject's immune system is responding to treatment.
On day 0, samples of tumor and any lymph nodes removed from armpit will be analyzed by the UPenn Department of Pathology according to standard practice.
Other Names:
|
Other: Arm 4 (Historical Controls)
Arm 4 will not receive any study treatment.
Subjects will undergo surgery on day 0 and follow a preoperative (Day 0) and postoperative blood (Day 30) and tissue (Day 0) sampling schedule.
|
Blood will be collected for laboratory studies and complete correlative studies to examine how the subject's immune system is responding to treatment.
On day 0, samples of tumor and any lymph nodes removed from armpit will be analyzed by the UPenn Department of Pathology according to standard practice.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Feasibility of preoperative pembrolizumab administration combined with radiation boost in patients with operable breast cancer
Time Frame: 2 years
|
Feasibility is defined as patient tolerability of the investigational treatment and no excessive delay in surgery in our participants.
The interval to breast-conserving surgery and mastectomy was based on review of our records in patients undergoing breast cancer surgery in 2016.
The average time to breast conservation surgery is 24.3 days (80% between 9 and 51 days) and for mastectomy with reconstruction 41.6 days (80% between 10 and 67 days).
|
2 years
|
Assess clinical response of treatment
Time Frame: 2 years
|
Evaluate clinical response using the following assessments:
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Assess immune response on pre- and post-treatment blood and tissue samples
Time Frame: 2 years
|
Assess immune response on pre- and post-treatment blood and tissue samples This study will track change in Ki67 + CD8 T cells in peripheral blood and in extent of tumor infiltrating lymphocytes (TIL).
|
2 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Julia C Tchou, MD, University of Pennsylvania
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- UPCC 04119
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Breast Cancer
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); Rutgers Cancer Institute of New JerseyActive, not recruitingStage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative Breast CancerUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedMale Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
Northwestern UniversityEisai Inc.UnknownMale Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative...United States
-
University of WashingtonTerminatedBreast Cancer | Breast Cancer Stage I | Breast Cancer Stage II | Breast Cancer Stage III | Breast Cancer Stage IIB | Breast Cancer Stage IIA | Breast Cancer Stage IIIA | Breast Cancer Stage IIIB | Breast Cancer Stage IIIcUnited States
-
CelgeneCompletedBreast Cancer | Metastatic Breast Cancer | Stage IV Breast Cancer | Triple-negative Breast Cancer | Recurrent Breast Cancer | Breast Tumor | Cancer of the Breast | Triple-negative Metastatic Breast Cancer | Estrogen Receptor- Negative Breast Cancer | HER2- Negative Breast Cancer | Progesterone Receptor- Negative...United States, United Kingdom, Italy, Germany, Spain, Canada, Portugal, Australia, Austria, Greece, Brazil, France
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedHER2-positive Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Estrogen Receptor-negative Breast Cancer | Estrogen Receptor-positive Breast Cancer | Progesterone Receptor-negative Breast Cancer | Progesterone Receptor-positive Breast...United States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Male Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...Susan G. Komen Breast Cancer FoundationCompletedStage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative Breast CancerUnited States
-
Ohio State University Comprehensive Cancer CenterCompletedStage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Stage III Breast CancerUnited States
Clinical Trials on Hypofractionated radiotherapy
-
Maria Sklodowska-Curie National Research Institute...RecruitingRecurrent Soft Tissue Sarcoma | Recurrent Sarcoma | Radiation Induced Neoplasms | Radiation-Induced CancerPoland
-
Hospital da BaleiaUnknownBreast Cancer | Radiation Toxicity
-
University of UtahNational Cancer Institute (NCI)RecruitingCervical Carcinoma | Endometrial CarcinomaUnited States
-
University Hospital HeidelbergRecruitingProstate CancerGermany
-
University of UtahActive, not recruitingStage 0 Breast Cancer | Stage I Breast Cancer | Stage II Breast Cancer | Invasive Breast Carcinoma | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Ductal Breast Carcinoma In SituUnited States
-
Cancer Institute and Hospital, Chinese Academy...RecruitingBreast CarcinomaChina
-
Medical University of GrazTerminatedProstate Cancer | Radiotherapy Side EffectAustria
-
Sunnybrook Health Sciences CentreCanadian Association of Radiation OncologyCompleted
-
Mayo ClinicNational Cancer Institute (NCI)Active, not recruitingAnatomic Stage I Breast Cancer AJCC v8 | Anatomic Stage IA Breast Cancer AJCC v8 | Anatomic Stage IB Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Prognostic Stage I Breast Cancer AJCC v8 | Prognostic Stage IA Breast Cancer AJCC v8 | Prognostic Stage IB Breast Cancer AJCC v8 | Prognostic Stage IIA Breast Cancer AJCC...United States
-
North China Petroleum Bureau General HospitalRecruiting