OCTANE: Adjuvant Liposomal Doxorubicin and Carboplatin for Early-stage Triple-negative Breast Cancer

Background Triple negative breast cancer (TNBC) is a subtype of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. TNBC is associated with a higher risk of recurrence and poorer prognosis compared to other breast cancer subtypes. Currently, the standard of care for early stage TNBC includes adjuvant chemotherapy, typically consisting of anthracyclines and taxanes. However, this regimen is associated with significant toxicities and adverse effects.

This clinical trial aims to evaluate the combination of liposomal doxorubicin and carboplatin as an adjuvant therapy for patients with early stage TNBC. Previous studies conducted in the neoadjuvant setting have shown promising results with this combination, indicating a reduction in the risk of recurrence. Additionally, the combination has demonstrated a more favorable tolerability profile compared to the current standard of care. Therefore, this trial seeks to assess the efficacy and safety of liposomal doxorubicin and carboplatin in the adjuvant setting for TNBC.

The primary objective of this clinical trial is to determine the efficacy of liposomal doxorubicin and carboplatin as adjuvant therapy for early stage TNBC. The efficacy will be measured by evaluating the recurrence-free survival (RFS) rate at a specified time point.

The secondary objectives of this study include: Characterizing the safety and toxicity profile of the combination therapy, as measured by the incidence and severity of adverse events using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Assessing the overall survival (OS) rate in patients receiving liposomal doxorubicin and carboplatin. Evaluating the pathological complete response (pCR) rate following the treatment regimen. Analyzing the disease-free survival (DFS) rate in patients treated with the combination therapy. In addition to the primary and secondary objectives, this study also aims to explore the following: Investigating changes in circulating tumor DNA (ctDNA) levels as a potential biomarker for treatment response and disease progression. Exploring correlations between specific genetic markers and treatment outcomes.

This study is a multicenter, open-label, phase II clinical trial. The study will enroll patients with early stage TNBC who have undergone surgical resection of the primary tumor. Patients in the study will receive adjuvant therapy consisting of liposomal doxorubicin and carboplatin. The dosing and administration schedule will be determined based on established guidelines and previous studies.

The sample size calculation will be based on statistical considerations, taking into account the primary endpoint of recurrence-free survival. A predetermined number of patients will be required to achieve adequate statistical power.

Eligible patients will be enrolled and undergo baseline assessments, including medical history, physical examination, laboratory tests, and imaging studies. Treatment will be initiated according to the predetermined dosing and administration schedule. Patients will be closely monitored throughout the study for treatment response, adverse events, and disease recurrence.

Follow-up visits will be scheduled at specified time intervals to assess long-term outcomes and collect additional data.

Inclusion criteria

• Newly diagnosed early stage triple negative breast cancer (TNBC) with a primary tumor size less than 2.5cm and nodal disease of N0/N1mi on final surgical pathology.
• Patients who have completed primary surgical treatment.
• Estrogen receptor (ER) expression of 20% or less, progesterone receptor (PgR) expression of 20% or less, and human epidermal growth factor receptor 2 (HER2) status 0-2+ by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) result of 2.0 or less.
• Participants with a history of prior cancers are allowed if there is no evidence of disease within the last five years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Baseline left ventricular ejection fraction (LVEF) greater than 50% (most recent measurement within the last 5 years).
• No prior history of treatment with anthracycline-based chemotherapy.
• Adequate bone marrow function:

• Absolute neutrophil count (ANC) greater than or equal to 1500/uL.
• Platelet count greater than or equal to 100,000/uL.
• Hemoglobin level greater than or equal to 9.0 g/dL.
• Adequate hepatic function:

• Total bilirubin less than or equal to 1.5 times the upper limit of normal (ULN).
• Aspartate aminotransferase (AST) levels (also known as serum glutamic-oxaloacetic transaminase, SGOT) less than or equal to 5 times the ULN.
• Alanine aminotransferase (ALT) levels (also known as serum glutamic-pyruvic transaminase, SGPT) less than or equal to five times the ULN.
• Participants with biliary obstruction must have restored biliary flow through the placement of an endoscopic common bile duct stent or percutaneous drainage.
• Adequate renal function, with a creatinine level less than 1.5 times the institutional ULN or a calculated creatinine clearance greater than or equal to 50 mL/min using the Cockcroft-Gault formula.
• Ability to understand the nature of the study protocol and provide written informed consent.
• Willingness and ability to comply with scheduled visits and treatment plans.

Exclusion criteria

• Participants with stage III-IV breast cancer.
• Uncontrolled hypertension, defined as systolic blood pressure greater than 190 mm Hg or diastolic blood pressure greater than 100 mm Hg.
• Active liver disease.
• Any condition, including the presence of laboratory abnormalities that, in the investigator's opinion, would place the participant at an unacceptable risk if they were to participate in the study.
• Pre-existing sensory neuropathy greater than grade 1.
• Clinically significant cardiac disease, such as congestive heart failure, symptomatic coronary artery disease, and uncontrolled cardiac arrhythmias, or a history of myocardial infarction within the last six months.
• Presence of a serious non-healing wound, ulcer, or bone fracture.
• Participants with uncontrolled and/or active infection with HIV, Hepatitis B, or Hepatitis C.
• Participants with a history of allergy or hypersensitivity to any of the study drugs.
• Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study.