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.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years and up |
| Sex | All |
| Enrollment | 2400 (estimated) |
| Sponsor | SWOG Cancer Research Network Research network |
| Drugs / interventions | pembrolizumab, radiation, prednisone, chemotherapy, immunotherapy, Cyclophosphamide, Doxorubicin |
| Locations | 963 sites (Birmingham, Alabama and 962 other locations) |
| Status | Recruiting |
| Started | September 15, 2023 |
| Main results expected | March 31, 2033 |
| Study ends | April 2033 |
| Registry record updated | November 5, 2025 |
| Trial ID | NCT05929768 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
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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
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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
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.