Anthracycline-Free Neoadjuvant Chemoimmunotherapy for Triple Negative Breast Cancer Patients

Launched by MEDICAL UNIVERSITY OF SOUTH CAROLINA · Feb 24, 2025

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment approach for patients with triple-negative breast cancer (TNBC) who cannot receive standard chemotherapy due to heart-related health issues. The study will test a combination of three medications—carboplatin, paclitaxel, and pembrolizumab—over a period of 12 to 18 weeks before surgery. Researchers want to see how well this treatment works in shrinking tumors in patients who have specific heart conditions and cannot tolerate traditional anthracycline-based therapies.

To participate in this trial, individuals must be at least 18 years old, have a measurable tumor larger than 1 cm, and have been diagnosed with TNBC at Stage II or III. They should also be fit enough to undergo surgery and have their heart health monitored by a doctor. Participants will receive the treatment and regular check-ups to monitor their progress, and they will need to agree to follow all study requirements, including signing consent forms. This trial is not yet recruiting participants, but it aims to provide a safer treatment option for those with specific health risks related to heart conditions.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Measurable or evaluable tumor in the breast larger than 1cm with or without axillary involvement
• • Ability to be followed by a cardiologist and/or primary care physician (PCP) for medication optimization of cardiac co-morbidities
• • Medically fit to undergo curative surgery as per the standard of care
• • Ability and willingness to comply with all study procedures and participant
• • Willingness to sign and date a written informed consent
• • Female or Male
• • Age 18 and above
• • Histologically confirmed TNBC Stage II, and Stage IIIA/B
• • The invasive tumor must be hormone receptor-negative or low, defined as both estrogen receptor (ER) and progesterone receptor (PR) staining present in \<10% of invasive cancer cells by IHC
• • HER2 negativity will be based on current ASCO-CAP guidelines for HER2 testing
• • In patients with multifocal disease, all the tumors should be Her2-negative
• • No previous chemotherapy, immunotherapy therapy, radiation therapy, or surgery for this breast cancer
• • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• * Have adequate organ function as defined below:
• * Hematological:
• • Absolute neutrophil count ≥ 1,500/uL
• • Platelets ≥ 100,000/uL
• • Leukocytes ≥ 3,000/uL
• • Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L (criteria must be met without erythropoietin dependency and without packed red blood cell transfusion within last 2 weeks)
• * Renal:
• • ---Creatinine ≤ 1.5 mg/dL and/or creatinine clearance ≥ 50 mL/min
• * Hepatic:
• • Total bilirubin ≤ 1.5x IULN, OR direct bilirubin ≤ IULN for participants with total bilirubin levels \> 1.5x IULN (unless history of Gilbert's disease. Participants with a history of Gilbert's disease must have total bilirubin ≤ 5 x institutional IULN).
• • AST(SGOT) and ALT(SPGT) ≤ 2.5x IULN
• * Coagulation:
• • ---International normalized ratio (INR) of coagulation OR prothrombin time (PT) OR activated partial thromboplastin time (aPTT) ≤ 1.5x IULN unless the patient is receiving anticoagulant therapy. If the patient is receiving anticoagulant therapy, PT or PTT is within the therapeutic range of the intended use of anticoagulants.
• • Serum albumin ≥ 3.0 g/dL
• • Patients with clinically and/or radiologically abnormal axillary lymph nodes should have pathological confirmation with image-guided biopsy/fine needle aspiration
• • Patients should have staging scans to exclude the possibility of metastatic disease when axillary imaging shows two or more abnormal lymph nodes or at the treating physician's discretion.
• • Patients with bilateral disease are eligible if they meet other eligibility criteria and both tumors are Her2 negative.
• • Neuropathy: no baseline neuropathy grade \> 2
• * A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• • Is not a woman of childbearing potential (WOCBP)
• • A WOCBP who agrees to use highly effective contraception for at least 1 month before screening and agreement to use such a method during study participation and for an additional 120 days after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• • Individuals identified as being at high risk for cardiotoxicity from anthracycline treatment.
• • Preexisting cardiomyopathy with Ejection Fraction (EF) between 25-49%
• • Severe valvular disease on echocardiogram
• • Previous exposure to Anthracyclines.
• • Previous exposure to high dose chest wall radiation \>30Gy
• • Participants who have experienced myocardial infarction, unstable angina pectoris, an arterial thrombotic event, or stroke, within the last 12 months but not less than 3 months ago.
• • Medium and High Risk for Congestive Heart Failure (CHF) at 3 years as defined by the Cardiotoxicity prediction tool from Ezaz et al. \[58\]
• • Patients declining anthracycline therapy after thorough discussion regarding its significant role in treating triple-negative breast cancer. Patients who are deemed ineligible for anthracyclines by their treating physician.
• Exclusion Criteria:
• • 30-day clearance period for any investigational agents or devices prior to starting the study drug, if applicable
• • Metastatic or inflammatory breast cancer
• • Patients deemed unfit to undergo curative surgery according to the standard of care.
• • Patients who have concomitant and/or previous malignancies within the last 5 years Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., ductal carcinoma in situ (DCIS), carcinoma in situ of the cervix) that have undergone potential curative therapy are NOT excluded.
• • History of hypersensitivity to compounds that are similar to carboplatin and paclitaxel
• • 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
• • Has received major surgery and has not recovered adequately from the toxicity and/or complications before starting study treatment
• • 30-day clearance period for live vaccines prior to starting study drug, if applicable
• • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy (7-day clearance period for steroid/immunosuppressant therapy prior to starting study drug, if applicable).
• • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs)
• • Has a history of solid organ transplant
• • Has a history of non-infectious pneumonitis that required high-dose steroids and/or has current pneumonitis
• • Has an active bacterial infection requiring systemic therapy
• • History of Human Immunodeficiency Virus (HIV)
• • History of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as detectable HCV RNA) infection
• • Known psychiatric or substance abuse disorders that would interfere with the requirements of the trial
• • Pregnant or breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment
• • Subject is a WOCBP who has had a positive urine pregnancy test within 24 hours prior to initiation of study treatment. Females will be determined to be not of child-bearing potential with a history of hysterectomy, tubal ligation, or age 45 or older with postmenopausal status \> 12 months
• • Patients are not allowed if they have uncontrolled hypertension (systolic BP \> 180 bpm or diastolic BP \> 100 bpm), or uncontrolled or symptomatic arrhythmia.
• • Patients are not allowed if the EF is less than 25%
• • Breast and axillary imaging (including ultrasound and MRI) within 42 days (6 weeks) prior to treatment initiation