ACTIVE_NOT_RECRUITING

Pre-op Pembro + Radiation Therapy in Breast Cancer (P-RAD)

Conditions

Triple Negative Breast Cancer Hormone Receptor Positive (HR+), HER2-negative Breast Cancer Biopsy-proven, Positive Lymph Node(s)Hormone Receptor Positive breast cancer Estrogen Receptor Positive breast cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This research trial is studying a combination of neoadjuvant radiotherapy (RT), immunotherapy (pembrolizumab) and chemotherapy for lymph node-positive, triple negative (TN) or hormone receptor positive/HER2-negative breast cancer. The names of the study interventions involved in this study are: * Radiation Therapy (RT) * Immunotherapy: Pembrolizumab (MK-3475) * Chemotherapies: * Paclitaxel * Doxorubicin (also called Adriamycin) * Cyclophosphamide * Carboplatin (optional, and in TN only) * Capecitabine (optional, and in TN only)

Official Title

P-RAD: A Randomized Study of Preoperative Chemotherapy, Pembrolizumab and No, Low or High Dose RADiation in Node-Positive, HER2-Negative Breast Cancer

Quick Facts

Study Start:2020-12-16

Study Completion:2027-08

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04443348

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Age ≥18 years old * Participant has non-metastatic, T1\-T2 and N1-3 and one of the following histologically confirmed disease subtypes: High-risk HR+/HER2-negative breast cancer is defined as ER≥1%, HER2-negative (\<2+ Her2 IHC or \<2.2 HER2/CEP17 ratio by FISH) and either histologic grade II-III or a high-risk genomic assay score (Oncotype RS\>25, high risk Mammaprint, PAM-50, EndoPredict or ProSigna score). * Note: Eligibility requires primary tumor size ≥1.0 cm in maximum diameter and axillary node-positive breast cancer * Primary breast tumor measuring ≥1.5 cm in maximal diameter as measured by any available standard of care imaging (mammogram, breast ultrasound, breast MRI). * Biopsy-proven, axillary lymph node-positive breast cancer at diagnosis. Note: Clinically node-positive disease is classified as cN1-3. cN1: without matted nodes, even if several/multiple appear matted on ultrasound or MRI; cN2: clinically fixed or matted nodes on examination or clinically or imaging-detected internal mammary node involvement. * Clips or fiducial placement within the biopsy-proven axillary lymph node and breast primary tumor are required. * Multifocal and multicentric disease is permitted; however only one breast tumor may be preoperatively boosted. * Synchronous bilateral invasive breast cancer is permitted; however only one breast tumor may be preoperatively boosted. * No indication of distant metastases. Staging scans are not required and are per the discretion of the treating physician. * Neoadjuvant chemotherapy (NAC) with paclitaxel, dose-dense doxorubicin and cyclophosphamide (dd AC) is planned. Note: For TNBC patients, administration of carboplatin is optional, as per MD choice. For HR+ patients, carboplatin will not be administered. * The boost volume is determined to be able to meet study dose constraints by the treating radiation oncologist. * Breast-conserving surgery or mastectomy +/- reconstruction is planned following NAC. * ECOG performance status score of 0 or 1. * Have adequate organ function as defined in the following table. Bloodwork must be collected within 10 days prior to the start of study treatment. * Hematological --- Absolute neutrophil count (ANC) ≥1500/µL * Platelets ≥100 000/µL * Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La * Renal * Hepatic * Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN * AST (SGOT) and ALT (SGPT) ≤2.5 × ULN * Coagulation * International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) * ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants * ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal. * Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks. * Creatinine clearance (CrCl) should be calculated per institutional standard. * Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies. * A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: * A male participant must agree to use a contraception as detailed in Appendix A of this protocol during the treatment period and for at least 4 months after the last dose of after the last dose of study treatment and refrain from donating sperm during this period. * Willingness to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol. * Willingness to undergo mandatory research biopsy of the breast tumor between weeks 2-3 of Cycle 1. * Written informed consent obtained from participant and ability for participant to comply with the requirements of the study. * Patients unable to read/write English are eligible to participate in the overall study, but will not be required to participate in the Patient-Reported Outcome questionnaires.	* HER2-positive breast cancer by ASCO/CAP guidelines (HER2 IHC 3+ or ≥ 2.2 HER2/CEP17 ratio by FISH) * Inflammatory (cT4d) breast cancer * Metastatic breast cancer (M1) * Contraindication(s) to breast-conserving therapy or mastectomy * Contraindication to radiation therapy including: prior ipsilateral breast or mantle RT, active scleroderma, systemic lupus erythematosis and pregnancy. * Prior ipsilateral breast, chest wall or thoracic radiotherapy * Prior ipsilateral invasive breast cancer, contralateral breast cancer or a known additional, invasive malignancy that is progressing or required active treatment in the last 5 years. * Has a known history of active tuberculosis (Bacillus tuberculosis * 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 prior to randomization. * Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. * Has known severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. * Participants with active, known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authorities. * Known active Hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (defined as HCV RNA \[qualitative\] is detected). Note: Testing for hepatitis B or hepatitis C is not required, unless mandated by local health authorities or institutional guidelines. * Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed. * Has had an allogenic tissue/solid organ transplant * A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of study treatment (see Appendix A). If the urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. * Prohibited Treatments and/or Therapies:Use of immunosuppressants and/or systemic corticosteroids is exclusionary, except the following in the absence of active autoimmune disease: * As premedication for chemotherapy * For the prevention of nausea in the three days following chemotherapy * Participants are permitted the use of corticosteroids with minimal systemic absorption (e.g. topical, ocular, intra-articular, intranasal and inhaled) * Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent permitted * Adrenal replacement steroid doses including doses \>10 mg daily prednisone is permitted * A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g. CT scan premedication against contrast dye allergy) or for treatment of non-autoimmune conditions (e.g. delayed-type hypersensitivity reaction caused by a contact allergen is permitted (used in the management of cancer or non-cancer-related illnesses). However, use of corticosteroids is allowed for the treatment of immune-related Adverse Events (irAEs), or adrenal insufficiency.

Inclusion Criteria

Exclusion Criteria

* Age ≥18 years old
* Participant has non-metastatic, T1\*-T2 and N1-3 and one of the following histologically confirmed disease subtypes:
* High-risk HR+/HER2-negative breast cancer is defined as ER≥1%, HER2-negative (\<2+ Her2 IHC or \<2.2 HER2/CEP17 ratio by FISH) and either histologic grade II-III or a high-risk genomic assay score (Oncotype RS\>25, high risk Mammaprint, PAM-50, EndoPredict or ProSigna score).
* Note: Eligibility requires primary tumor size ≥1.0 cm in maximum diameter and axillary node-positive breast cancer
* Primary breast tumor measuring ≥1.5 cm in maximal diameter as measured by any available standard of care imaging (mammogram, breast ultrasound, breast MRI).
* Biopsy-proven, axillary lymph node-positive breast cancer at diagnosis. Note: Clinically node-positive disease is classified as cN1-3. cN1: without matted nodes, even if several/multiple appear matted on ultrasound or MRI; cN2: clinically fixed or matted nodes on examination or clinically or imaging-detected internal mammary node involvement.
* Clips or fiducial placement within the biopsy-proven axillary lymph node and breast primary tumor are required.
* Multifocal and multicentric disease is permitted; however only one breast tumor may be preoperatively boosted.
* Synchronous bilateral invasive breast cancer is permitted; however only one breast tumor may be preoperatively boosted.
* No indication of distant metastases. Staging scans are not required and are per the discretion of the treating physician.
* Neoadjuvant chemotherapy (NAC) with paclitaxel, dose-dense doxorubicin and cyclophosphamide (dd AC) is planned. Note: For TNBC patients, administration of carboplatin is optional, as per MD choice. For HR+ patients, carboplatin will not be administered.
* The boost volume is determined to be able to meet study dose constraints by the treating radiation oncologist.
* Breast-conserving surgery or mastectomy +/- reconstruction is planned following NAC.
* ECOG performance status score of 0 or 1.
* Have adequate organ function as defined in the following table. Bloodwork must be collected within 10 days prior to the start of study treatment.
* Hematological --- Absolute neutrophil count (ANC) ≥1500/µL
* Platelets ≥100 000/µL
* Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La
* Renal
* Hepatic
* Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN
* AST (SGOT) and ALT (SGPT) ≤2.5 × ULN
* Coagulation
* International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT)
* ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
* ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.
* Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
* Creatinine clearance (CrCl) should be calculated per institutional standard.
* Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.
* A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
* A male participant must agree to use a contraception as detailed in Appendix A of this protocol during the treatment period and for at least 4 months after the last dose of after the last dose of study treatment and refrain from donating sperm during this period.
* Willingness to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.
* Willingness to undergo mandatory research biopsy of the breast tumor between weeks 2-3 of Cycle 1.
* Written informed consent obtained from participant and ability for participant to comply with the requirements of the study.
* Patients unable to read/write English are eligible to participate in the overall study, but will not be required to participate in the Patient-Reported Outcome questionnaires.

* HER2-positive breast cancer by ASCO/CAP guidelines (HER2 IHC 3+ or ≥ 2.2 HER2/CEP17 ratio by FISH)
* Inflammatory (cT4d) breast cancer
* Metastatic breast cancer (M1)
* Contraindication(s) to breast-conserving therapy or mastectomy
* Contraindication to radiation therapy including: prior ipsilateral breast or mantle RT, active scleroderma, systemic lupus erythematosis and pregnancy.
* Prior ipsilateral breast, chest wall or thoracic radiotherapy
* Prior ipsilateral invasive breast cancer, contralateral breast cancer or a known additional, invasive malignancy that is progressing or required active treatment in the last 5 years.
* Has a known history of active tuberculosis (Bacillus tuberculosis
* 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 prior to randomization.
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* Has known severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
* Participants with active, known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
* Known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authorities.
* Known active Hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (defined as HCV RNA \[qualitative\] is detected). Note: Testing for hepatitis B or hepatitis C is not required, unless mandated by local health authorities or institutional guidelines.
* Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed.
* Has had an allogenic tissue/solid organ transplant
* A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of study treatment (see Appendix A). If the urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
* Prohibited Treatments and/or Therapies:Use of immunosuppressants and/or systemic corticosteroids is exclusionary, except the following in the absence of active autoimmune disease:
* As premedication for chemotherapy
* For the prevention of nausea in the three days following chemotherapy
* Participants are permitted the use of corticosteroids with minimal systemic absorption (e.g. topical, ocular, intra-articular, intranasal and inhaled)
* Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent permitted
* Adrenal replacement steroid doses including doses \>10 mg daily prednisone is permitted
* A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g. CT scan premedication against contrast dye allergy) or for treatment of non-autoimmune conditions (e.g. delayed-type hypersensitivity reaction caused by a contact allergen is permitted (used in the management of cancer or non-cancer-related illnesses). However, use of corticosteroids is allowed for the treatment of immune-related Adverse Events (irAEs), or adrenal insufficiency.

Contacts and Locations

Principal Investigator

Laura M Spring, MD

PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Study Locations (Sites)

Sibley Memorial Hospital

Washington, District of Columbia, 20016

United States

Johns Hopkins

Baltimore, Maryland, 21231

United States

Massachusetts General Hospital

Boston, Massachusetts, 02115

United States

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Mayo Clinic - Rochester

Rochester, Minnesota, 55905

United States

Montefiore Medical Center

Bronx, New York, 10467

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

University of North Carolina Medical Center

Chapel Hill, North Carolina, 27514

United States

Duke University Medical Center

Durham, North Carolina, 27710

United States

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: Laura M. Spring, MD

Laura M Spring, MD, PRINCIPAL_INVESTIGATOR, Massachusetts General Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-12-16

Study Completion Date2027-08

Study Record Updates

Study Start Date2020-12-16

Study Completion Date2027-08

Terms related to this study

Keywords Provided by Researchers

Triple Negative Breast Cancer
Hormone Receptor Positive breast cancer
Estrogen Receptor Positive breast cancer

Additional Relevant MeSH Terms

Triple Negative Breast Cancer
Hormone Receptor Positive (HR+), HER2-negative Breast Cancer
Biopsy-proven, Positive Lymph Node(s)