Neoadjuvant oral paclitaxel with subcutaneous pertuzumab and trastuzumab for HER2-positive breast cancer

A Single-Arm Clinical Study to Evaluate the Efficacy and Safety of Neoadjuvant Oral Paclitaxel Plus Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Injection in Patients With HER2-positive Breast Cancer

This trial tests whether taking oral paclitaxel together with subcutaneous pertuzumab and trastuzumab before surgery helps people with HER2-positive breast cancer achieve a complete tumor response on pathology.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 112 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Academic / other)
• Drugs / interventions: pertuzumab, trastuzumab
• Locations: 9 sites (Beijing, Beijing Municipality and 8 other locations)
• Trial ID: NCT07095023 on ClinicalTrials.gov

What this trial studies

OPTIMAL-BC is a multicenter, single-arm study using a Simon two-stage design that gives oral paclitaxel plus a fixed-dose subcutaneous combination of pertuzumab and trastuzumab every three weeks for six cycles prior to surgery. All participants undergo surgery according to local guidelines after completing neoadjuvant therapy. The primary endpoint is total pathological complete response (tpCR, ypT0/is, ypN0). Key eligibility includes adults 18 to 75 with HER2-positive invasive breast cancer (T1c–4, N0–3, M0, excluding T1cN0M0) and adequate cardiac and organ function.

Who should consider this trial

Good fit: Adults 18–75 with histologically confirmed HER2-positive invasive breast cancer (T1c–4, N0–3, M0 except T1cN0M0), ECOG 0–1, LVEF ≥50%, and adequate blood and organ function are ideal candidates.

Not a fit: Patients with metastatic disease, the protocol-excluded very small tumors (T1cN0M0), poor cardiac function, or inadequate blood/organ counts are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this regimen could increase rates of complete tumor eradication before surgery while offering a more convenient oral chemotherapy and subcutaneous antibody option.

How similar studies have performed: Prior neoadjuvant trials combining trastuzumab and pertuzumab with taxanes have improved pathological complete response rates, but using oral paclitaxel with a subcutaneous fixed-dose antibody combination is less tested and relatively novel.

Eligibility criteria

Inclusion Criteria:

Aged 18-75 years old. Histologically confirmed HER2-positive invasive breast cancer with clinical stages T1c-4, N0-3, and M0 (excluding T1cN0M0), according to the 8th American Joint Committee on Cancer (AJCC) edition BC staging system HER2 overexpression was defined as immunohistochemistry (IHC) 3+ or 2+ with HER2 gene amplification, determined by fluorescence in situ hybridization (FISH).

Baseline left ventricular ejection fraction (LVEF) of ≥50%. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.

The functional level of major organs must meet the following requirements (no blood transfusion and no use of white blood cell, red blood cell and platelet-raising drugs within 2 weeks before the first dose):

* Absolute neutrophil count ≥ 1,500/mcL
* Platelets ≥ 100,000/mcL
* Hemoglobin ≥ 9.0 g/dL
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
* Alanine aminotransferase and aspartate aminotransferase (ALT/AST) ≤1.5×ULN
* Blood urea nitrogen and serum creatinine ≤1.5×ULN
* Creatinine clearance (Ccr) ≥50 ml/min (Cockcroft-Gault formula) Signature of informed consent

Exclusion Criteria:

* History of invasive breast cancer. Bilateral breast cancer or inflammatory breast cancer . Prior excisional and/or incisional biopsy of the primary tumor and/or axillary lymph nodes.

Prior systemic therapy for breast cancer. History of life-threatening hypersensitivity reactions or known hypersensitivity to any component of the investigational drug.

Participation in another clinical trial of a drug or medical device within 4 weeks prior to the first dose and/or receipt of investigational drug/device during the trial.

Major surgery within 28 days prior to the first dose or planned major surgery during the study period.

History of other malignancies within the past 5 years, except for carcinoma in situ of the cervix, non-melanoma skin cancer, localized prostate cancer, or ductal carcinoma in situ.

Active tuberculosis or other severe infectious diseases requiring systemic treatment, including but not limited to bacteremia, severe pneumonia, and other serious infections.

History of immunodeficiency or autoimmune diseases, including but not limited to HIV infection (HIV antibody positive), systemic lupus erythematosus, rheumatoid arthritis, or history of organ transplantation.

History of cardiovascular or cerebrovascular diseases, including:

* Unstable angina;
* Clinically significant arrhythmias requiring medication;
* Myocardial infarction within the past 6 months;
* Heart failure or second-degree or higher atrioventricular block;
* Cerebral infarction (excluding lacunar infarction) or cerebral hemorrhage within the past 6 months.

Poorly controlled hypertension (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg despite regular medication), or history of hypertensive crisis or hypertensive encephalopathy.

Unsuitability for oral administration of the investigational drug, as judged by the investigator, including:

* Clinically significant or uncontrolled congenital or acquired gastrointestinal diseases;
* Diseases that may affect drug administration, gastric entry, or absorption (e.g., intestinal obstruction, Crohn's disease, ulcerative colitis).

Pregnant or breastfeeding women; women of childbearing potential with a positive pregnancy test at screening; or those unwilling to use effective contraception during the study and for 6 months after the last dose.

Where this trial is running

Beijing, Beijing Municipality and 8 other locations

• Peking University Cancer Hospital — Beijing, Beijing Municipality, China (Not_yet_recruiting)
• Guangdong Women and children Hospital — Guangzhou, Guangdong, China (Not_yet_recruiting)
• Sun Yat-sen Memorial Hospital — Guangzhou, Guangdong, China (Recruiting)
• Cancer Hospital of Shantou University Medical College — Shantou, Guangdong, China (Not_yet_recruiting)
• Guangxi Provincial Cancer Hospital — Nanning, Guangxi, China (Not_yet_recruiting)
• The Affiliated Hospital of Guizhou Medical University — Guiyang, Guizhou, China (Not_yet_recruiting)
• Hainan Central Hospital — Haikou, Hainan, China (Not_yet_recruiting)
• the First Affiliated Hospital of Wenzhou Medical University — Wenzhou, Zhejiang, China (Not_yet_recruiting)
• Peking University Shenzhen Hospita — Shenzhen, China (Not_yet_recruiting)

Study contacts

• Principal investigator: Qiang Liu, PhD — Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Study coordinator: Qiang Liu, PhD

Conditions Breast Cancers