Clinical trial Recruiting at 923 sites Phase 3 Interventional Ages 18 and up

Shorter chemotherapy and immunotherapy for early-stage triple negative breast cancer

Official title: Shorter Anthracycline-Free Chemo Immunotherapy Adapted to Pathological Response in Early Triple Negative Breast Cancer (SCARLET), A Randomized Phase III Study

Run by SWOG Cancer Research Network · NCT05929768 · Data updated 2026-11-12

This study is testing whether a shorter treatment plan of chemotherapy and immunotherapy without certain strong drugs can help people with early-stage triple negative breast cancer do better than the usual longer treatment.

More Anatomic Stage II Breast Cancer AJCC v8 trials

Quick facts

PhasePhase 3
Study typeInterventional
Ages18 Years and up
SexAll
Enrollment2400 (estimated)
SponsorSWOG Cancer Research Network
Research network
Drugs / interventionspembrolizumab, radiation, prednisone, chemotherapy, immunotherapy, Cyclophosphamide, Doxorubicin
Locations963 sites (Birmingham, Alabama and 962 other locations)
StatusRecruiting
StartedSeptember 15, 2023
Main results expectedMarch 31, 2033
Study endsApril 2033
Registry record updatedNovember 5, 2025
Trial IDNCT05929768 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Ideal candidates are individuals with histologically confirmed early-stage triple negative breast cancer who meet specific staging and receptor status criteria.

Probably not a fit

Patients with hormone receptor-positive or HER2-positive breast cancer may not benefit from this study.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase III trial evaluates the effectiveness of a shorter course of chemotherapy and immunotherapy without anthracycline drugs for patients with early-stage triple negative breast cancer. Participants will be randomized to receive either an anthracycline-free regimen or the standard treatment that includes anthracyclines, with the primary goal of comparing breast cancer event-free survival rates. Secondary objectives include assessing pathological complete response rates, safety, and patient-reported outcomes related to fatigue. The study also aims to explore the role of tumor infiltrating lymphocytes in treatment response.

Why it matters

Potential benefit: If successful, this approach could lead to more effective and better-tolerated treatment options for patients with early-stage triple negative breast cancer.

How similar studies have gone: Other studies have shown promising results with anthracycline-free regimens in similar patient populations, suggesting potential for success in this approach.

Who can join: the full rules

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Participants must have histologically confirmed estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative breast cancer (TNBC) defined as ER \< 5%, PR \< 5%, and HER2 negative (per 2020 American Society of Clinical Oncology \[ASCO\] College of American Pathologists \[CAP\] guidelines)

  * NOTE: Participants with weakly ER or PR positive disease, defined as ER and/or PR between 1-4% by immunohistochemistry, are eligible if adjuvant endocrine therapy is not recommended/planned by the treating physician
* Participants must have American Joint Committee on Cancer (AJCC) 8 anatomic tumor clinical stage either

  * T2-T4, N0, M0 or
  * T1-T3, N1-2, M0
  * Note: All participants with clinically suspicious nodes must undergo core needle biopsy or fine needle biopsy per standard clinical practice to pathologically confirm nodal status
* Participants must have breast and axillary imaging with mammogram and/or ultrasound and/or magnetic resonance imaging (MRI) within 49 days prior to randomization

  * Note: Participants with bilateral invasive breast cancer are eligible if both breast cancers are ER-negative, PR-negative, and HER2-negative provided they meet the other eligibility criteria
* Participants must not have T4/N+, any N3, or inflammatory breast cancer
* Participants must not have metastatic disease (M1)
* Participants must not have received prior systemic therapy or radiation therapy with curative intent for the current breast cancer
* Participants must not have had previous definitive ipsilateral breast surgery for the current breast cancer
* Participants must not have current or anticipated use of other investigational agents while participating in this study
* Participants must not have history of allergic reactions attributed to compounds of similar chemical or biologic composition as study agents
* Participants must not have severe hypersensitivity (\>= grade 3) to pembrolizumab or any of its excipients
* Participants must not have 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 (e.g. CTLA-4, OX-40, CD137)
* Participants must not be currently participating in or have participated in a study of an investigational agent or used an investigational device within 28 days prior to randomization
* Participants must be \>= 18 years old
* Participants must have Zubrod performance status of 0-2
* Participants with evidence of peripheral neuropathy must have it at =\< grade 1, by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0, within 28 days prior to randomization
* Participants must have a complete medical history and physical exam within 28 days prior to randomization
* Hemoglobin \>= 9.0 g/dL or \>= 5.6 mol/L (within 28 days prior to randomization)

  * (Criteria must be met without erythropoietin dependency and without packed red blood cell transfusion within last 2 weeks)
* Leukocytes \>= 3 x 10\^3/uL (within 28 days prior to randomization)
* Absolute neutrophil count \>= 1.5 x 10\^3/uL (within 28 days prior to randomization)
* Platelets \>= 100 x 10\^3/uL (within 28 days prior to randomization)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN), OR direct bilirubin =\< IULN for participants with total bilirubin \> 1.5 x IULN (unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =\< 5 x institutional IULN) (within 28 days prior to randomization)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x institutional upper limit of normal (ULN) (within 28 days prior to randomization)
* Participants must have a serum creatinine =\< the IULN OR calculated creatinine clearance \>= 50 mL/min/1.73m\^2 using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration
* Participants must have adequate cardiac function. Participants must have left ventricular ejection fraction \>= 50% as assessed by either echocardiography (ECHO) or multigated acquisition scan (MUGA) assessed within 28 days prior to registration. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification and must be class 2B or better
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at randomization and have undetectable viral load test on the most recent test results obtained within 6 months prior to randomization
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to randomization, if indicated

  * Note: No testing for Hepatitis B is required unless mandated by local health authority
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to randomization, if indicated

  * Note: No testing for hepatitis C is required unless mandated by local health authority
* Participants with history of diabetes must not have uncontrolled diabetes in the opinion of the treating investigator
* Participants must not have uncontrolled hypertension in the opinion of the treating investigator
* Participants must not have had a major surgery within 14 days prior to randomization. Participants must have fully recovered from the effects of prior major surgery in the opinion of the treating investigator
* Participants must not have severe or active infections within 14 days prior to Randomization, including but not limited to hospitalization for infection, bacteremia, or severe pneumonia
* Participants must not have a diagnosis of immunodeficiency and be receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization
* Participants must not have active autoimmune disease that has required systemic treatment in 2 years prior to randomization (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
* Participants must not have a history of (non-infectious) pneumonitis that required steroids, or has current (non-infectious) pneumonitis
* Participants must not have received a live vaccine within 30 days prior to randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist \[registered trademark\]) are live attenuated vaccines and are not allowed
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the treatment regimen
* Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must have one (1) physical 4-5-micron single hematoxylin and eosin (H\&E) slide from the archival pretreatment diagnostic biopsy available for submission
* Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
* Participants who can complete questionnaires in English, Spanish, or French must be offered the opportunity to participate in the Patient-Reported Outcome study
* NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

  * Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
  * For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
* As part of the registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Where it's running

  • University of Alabama at Birmingham Cancer Center
    Birmingham, Alabama, United States
    Recruiting
  • Anchorage Associates in Radiation Medicine
    Anchorage, Alaska, United States
    Recruiting
  • Alaska Breast Care and Surgery LLC
    Anchorage, Alaska, United States
    Recruiting
  • Alaska Oncology and Hematology LLC
    Anchorage, Alaska, United States
    Recruiting
  • Alaska Women's Cancer Care
    Anchorage, Alaska, United States
    Recruiting
  • Katmai Oncology Group
    Anchorage, Alaska, United States
    Recruiting
Show 44 more locations
  • Providence Alaska Medical Center
    Anchorage, Alaska, United States
    Recruiting
  • Fairbanks Memorial Hospital
    Fairbanks, Alaska, United States
    Recruiting
  • Kingman Regional Medical Center
    Kingman, Arizona, United States
    Recruiting
  • Cancer Center at Saint Joseph's
    Phoenix, Arizona, United States
    Recruiting
  • Highlands Oncology Group - Fayetteville
    Fayetteville, Arkansas, United States
    Recruiting
  • Mercy Hospital Fort Smith
    Fort Smith, Arkansas, United States
    Recruiting
  • NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
    Jonesboro, Arkansas, United States
    Recruiting
  • CARTI Cancer Center
    Little Rock, Arkansas, United States
    Recruiting
  • University of Arkansas for Medical Sciences
    Little Rock, Arkansas, United States
    Recruiting
  • Highlands Oncology Group - Rogers
    Rogers, Arkansas, United States
    Recruiting
  • Highlands Oncology Group
    Springdale, Arkansas, United States
    Recruiting
  • Kaiser Permanente-Anaheim
    Anaheim, California, United States
    Recruiting
  • Mission Hope Medical Oncology - Arroyo Grande
    Arroyo Grande, California, United States
    Recruiting
  • PCR Oncology
    Arroyo Grande, California, United States
    Recruiting
  • Sutter Auburn Faith Hospital
    Auburn, California, United States
    Recruiting
  • Sutter Cancer Centers Radiation Oncology Services-Auburn
    Auburn, California, United States
    Recruiting
  • Kaiser Permanente-Baldwin Park
    Baldwin Park, California, United States
    Recruiting
  • Kaiser Permanente-Bellflower
    Bellflower, California, United States
    Recruiting
  • Alta Bates Summit Medical Center-Herrick Campus
    Berkeley, California, United States
    Recruiting
  • Tower Cancer Research Foundation
    Beverly Hills, California, United States
    Recruiting
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    Burbank, California, United States
    Recruiting
  • Mills-Peninsula Medical Center
    Burlingame, California, United States
    Recruiting
  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    Cameron Park, California, United States
    Recruiting
  • Mercy Cancer Center - Carmichael
    Carmichael, California, United States
    Recruiting
  • Mercy San Juan Medical Center
    Carmichael, California, United States
    Recruiting
  • Eden Hospital Medical Center
    Castro Valley, California, United States
    Recruiting
  • Sutter Davis Hospital
    Davis, California, United States
    Recruiting
  • City of Hope Comprehensive Cancer Center
    Duarte, California, United States
    Recruiting
  • Mercy Cancer Center - Elk Grove
    Elk Grove, California, United States
    Recruiting
  • Stanford Cancer Center Emeryville
    Emeryville, California, United States
    Recruiting
  • Kaiser Permanente-Fontana
    Fontana, California, United States
    Recruiting
  • Palo Alto Medical Foundation-Fremont
    Fremont, California, United States
    Recruiting
  • Kaiser Permanente South Bay
    Harbor City, California, United States
    Recruiting
  • City of Hope at Irvine Lennar
    Irvine, California, United States
    Recruiting
  • Kaiser Permanente-Irvine
    Irvine, California, United States
    Recruiting
  • City of Hope Antelope Valley
    Lancaster, California, United States
    Recruiting
  • Loma Linda University Medical Center
    Loma Linda, California, United States
    Recruiting
  • Kaiser Permanente Los Angeles Medical Center
    Los Angeles, California, United States
    Recruiting
  • Kaiser Permanente West Los Angeles
    Los Angeles, California, United States
    Recruiting
  • Cedars Sinai Medical Center
    Los Angeles, California, United States
    Recruiting
  • Contra Costa Regional Medical Center
    Martinez, California, United States
    Recruiting
  • Mercy Cancer Center
    Merced, California, United States
    Recruiting
  • Memorial Medical Center
    Modesto, California, United States
    Recruiting
  • Palo Alto Medical Foundation-Camino Division
    Mountain View, California, United States
    Recruiting

+913 more sites. See ClinicalTrials.gov for the full list.

Study contacts

  • Principal investigator: Priyanka Sharma — SWOG Cancer Research Network
  • Study coordinator: Alicia Aranda
  • Email: aaranda@swog.org
  • Phone: 210-614-8808

Similar studies

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How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.