Breast Cancer Clinical Trial

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

Summary

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)

View Full Description

Full Description

The main purpose of this study is to find out what is the best dose of preoperative RT when combined with pembrolizumab and chemotherapy. The study will assess if combining the RT with the immunotherapy agent, pembrolizumab, will increase the ability of the immune system to destroy cancer cells.

The research study procedures include: screening for eligibility and study treatment, including evaluations and follow-up visits.

The study aims to assess the effectiveness of pembrolizumab (study drug) with or without RT directed to the breast tumor. Participants will then undergo neoadjuvant chemotherapy with pembrolizumab, followed by treatment that can consist of one or more of the following:

Pembrolizumab (optional, per MD discretion)

Standard of Care Treatment

Breast surgery (lumpectomy or mastectomy) and axillary surgery
Adjuvant radiation to the entire breast or chest wall, plus or minus the lymph nodes after surgery
Adjuvant chemotherapy (optional Capecitabine for TNBC patients)
Hormone therapy

Participants will be randomized to 1 of 3 groups. Neither the participant not the research doctor will choose the group that the participant is assigned to. However, the participant will be notified of the group prior to the start of study treatment. Participants will receive study treatment for up to 13 months. Participants will be followed for 2 years after the end of the study treatment.

It is expected that a total of 120 people will be participating in total.

This research study is a randomized, phase II study. The U.S. Food and Drug Administration (FDA) has not approved pembrolizumab for your specific disease, but it has been approved for other uses. The U.S. Food and Drug Administration (FDA) has approved the chemotherapies being used in this study (Paclitaxel, Doxorubicin, Cyclophosphamide, Carboplatin, Capecitabine).

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Age ≥18 years old

Participant has non-metastatic, T1*-T2 and N1-3 and one of the following histologically confirmed disease subtypes:

-- Triple negative breast cancer is defined as ER-negative (<1% cells), PR-negative (<1% cells) and HER2-negative (<2+ HER2 IHC or <2.2 HER2/CEP17 ratio by FISH), as per testing at local institution

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.

--Note: For patients with multifocal disease and are randomized to receive a preoperative RT boost, all sites of multifocal disease should be contained within the pre-operative boost volume. Subsequently, these patients will not need a post-op boost.

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

--- Creatinine ≤1.5 × ULN OR Measured or calculated b creatinine clearance (GFR can also be used in place of creatinine or CrCl) OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN

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) Not a woman of childbearing potential (WOCBP) OR b) A WOCBP who agrees to follow the contraceptive guidance throughout the study and for at least 4 months after the last dose of pembrolizumab in such a manner that the risk of pregnancy is minimized.

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.

Exclusion Criteria:

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.

--Note: All cardiac implantable electronic devices are permitted, provided that methods to assess radiation doses and minimize damage to the devices during RT is planned, per institutional guidelines.

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.

--Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or cervical carcinoma in situ that has undergone potentially curative therapy and a previous diagnosis of ductal carcinoma in situ are not excluded.

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.

--Note: Participants must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be eligible. If participant received major surgery, she/he must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.

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.

Study is for people with:

Breast Cancer

Phase:

Phase 2

Estimated Enrollment:

120

Study ID:

NCT04443348

Recruitment Status:

Recruiting

Sponsor:

Laura M. Spring, MD

Check Your Eligibility

Let’s see if you might be eligible for this study.

What is your age and gender ?

Submit

There are 9 Locations for this study

See Locations Near You

Sibley Memorial Hospital
Washington District of Columbia, 20016, United States More Info
Cesar Santa-Maria, MD
Contact
202-660-6500
Cesar Santa-Maria, MD
Principal Investigator
Johns Hopkins
Baltimore Maryland, 21231, United States More Info
Cesar Santa-Maria, MD
Contact
410-955-8893
Cesar Santa-Maria, MD
Principal Investigator
Massachusetts General Hospital
Boston Massachusetts, 02115, United States More Info
Laura M Spring, MD
Contact
617-726-6500
[email protected]
Laura M Spring, MD
Principal Investigator
Dana Farber Cancer Institute
Boston Massachusetts, 02215, United States More Info
Laura Warren, MD
Contact
617-632-4739
[email protected]
Laura Warren, MD
Principal Investigator
Mayo Clinic - Rochester
Rochester Minnesota, 55905, United States More Info
Robert Mutter, MD
Contact
507-284-2511
Robert Mutter, MD
Principal Investigator
Montefiore Medical Center
Bronx New York, 10467, United States More Info
Jana Fox, MD
Contact
718-920-7750
Jana Fox, MD
Principal Investigator
Memorial Sloan Kettering Cancer Center
New York New York, 10065, United States More Info
Atif Khan, MD
Contact
848-225-6334
Atif Khan, MD
Principal Investigator
University of North Carolina Medical Center
Chapel Hill North Carolina, 27514, United States More Info
Gaorav Gupta, MD, PhD
Contact
[email protected]
Gaorav Gupta, MD, PhD
Principal Investigator
Duke University Medical Center
Durham North Carolina, 27710, United States More Info
Rachel Blitzblau, MD
Contact
919-660-2100
Shelley Hwang, MD, MPH
Contact
919-668-6688
Rachel Blitzblau, MD
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 2

Estimated Enrollment:

120

Study ID:

NCT04443348

Recruitment Status:

Recruiting

Sponsor:


Laura M. Spring, MD

How clear is this clinincal trial information?

×

Introducing, the Journey Bar

Use this bar to access information about the steps in your cancer journey.