Paclitaxel Oral Solution in HER2-Positive Breast Cancer Neoadjuvant Therapy: A Dose-Finding Study (GBCF002)

A Dose-Finding Study of Paclitaxel Oral Solution in Neoadjuvant Therapy for Patients With HER2-Positive Breast Cancer

This is a multicenter, open-label, dose-finding trial using a backfill Bayesian optimal interval (BF-BOIN) design to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) for paclitaxel oral solution combined with anti-HER2 treatment. Eligible HER2-positive breast cancer patients receive 6 cycles of neoadjuvant THP regimen(paclitaxel oral solution + trastuzumab+pertuzumab) and are enrolled in three cohorts at oral paclitaxel dose levels 1-3 (125, 150, 175 mg/m²).

Study Overview

• Status: Recruiting
• Conditions: HER2 + Breast Cancer
• Intervention / Treatment: Combination product: Paclitaxel oral solution plus Trastuzumab and Pertuzumab

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Shu Liu, PhD; Phone Number: 86- 13908516963; Email: Drliushu@163.com
• Study Contact Backup: Name: Yu Ren, PhD

Study Locations

• China
  • Guizhou
    • Guiyang, Guizhou, China
      • Recruiting
      • The Affiliated Hospital of Guizhou Medical University
      • Contact: Yu Ren
      • Contact: Shu Liu, PhD; Phone Number: 86- 13908516963; Email: Drliushu@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female, aged 18 to 70 years.
2. Histologically confirmed invasive breast cancer by core needle biopsy; clinical stage T1c-4, N0-3, M0 per the AJCC 8th edition breast cancer staging system (T1cN0M0 excluded).
3. HER2-positive status defined as IHC 3+ or IHC 2+ with FISH amplification.
4. Left ventricular ejection fraction (LVEF) ≥ 50%.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. Adequate organ function assessed within 14 days prior to first dose of study drug, without blood transfusion or growth-factor support, meeting the following:

   1. Hematology: absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelet count (PLT) ≥ 100 × 10⁹/L; hemoglobin (Hb) ≥ 90 g/L.
   2. Blood chemistry: total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN; blood urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN; creatinine clearance (CrCl) ≥ 50 mL/min by the Cockcroft-Gault formula.
7. Voluntary participation with signed informed consent, good compliance, and willingness to attend follow-up.

Exclusion Criteria:

1. History of prior invasive breast cancer.
2. Bilateral breast cancer, or inflammatory breast cancer (e.g., erythema and/or skin involvement and/or pathological evidence of tumor cells in dermal lymphatics).
3. Prior excisional and/or incisional biopsy of the primary tumor and/or axillary lymph nodes.
4. Prior systemic therapy for breast cancer.
5. History of life-threatening hypersensitivity reaction, or known allergy to any component of the study drug.
6. Participation in another drug or medical device clinical trial within 4 weeks prior to first dose, with receipt of investigational product or device.
7. Major surgery within 28 days prior to first dose, or planned major surgery during the study.
8. Other malignancy within the past 5 years (except cervical carcinoma in situ, non-melanoma skin cancer, localized prostate cancer, and ductal carcinoma in situ).
9. Active tuberculosis or other serious infectious disease, including but not limited to bacteremia, severe infectious pneumonia, or other severe infection requiring systemic therapy.
10. History of immunodeficiency or other autoimmune disease, including but not limited to HIV infection (positive HIV antibody), systemic lupus erythematosus, rheumatoid arthritis, or history of organ transplantation.
11. History of any of the following cardiovascular/cerebrovascular diseases: (1) unstable angina; (2) clinically significant or medication-requiring arrhythmia; (3) myocardial infarction within 6 months; (4) heart failure, or second-degree or higher atrioventricular block; (5) cerebral infarction (except lacunar infarction) or cerebral hemorrhage within 6 months.
12. Uncontrolled hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg despite regular antihypertensive medication), or history of hypertensive crisis or hypertensive encephalopathy.
13. Uncontrolled concurrent illness or condition (including significant psychiatric or social condition) that, in the investigator's judgment, may affect compliance with study procedures.
14. Requirement for long-term use of proton pump inhibitors or H2 receptor antagonists during the study; or use of strong inducers or inhibitors of CYP3A4 or CYP2C8 within 2 weeks prior to first study-drug administration.
15. In the investigator's judgment, subjects unsuitable or unwilling to take oral study drug: (1) clinically significant or uncontrolled congenital or acquired gastrointestinal disease; (2) diagnosed disease that may affect administration, gastrointestinal transit, or absorption of the study drug, or adherence to oral study drug, including intestinal obstruction and inflammatory bowel disease (Crohn's disease and ulcerative colitis), peptic ulcer, uncontrolled nausea, vomiting, or diarrhea; (3) presence or suspected impairment of bile secretion.
16. Pregnant or lactating women; women of childbearing potential with a positive pregnancy test at screening; or those unwilling to use effective contraception throughout the study and for 3 months after the last dose.
17. Any other condition that, in the investigator's opinion, makes the subject unsuitable for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose-level 1 cohort; The dose of paclitaxel oral solution is 125mg/m2.	Combination product: Paclitaxel oral solution plus Trastuzumab and Pertuzumab; Eligible patients in three cohorts receive 6 neoadjuvant THP cycles: paclitaxel oral solution at 125/150/175 mg/m² BID (D1, D8, D15), and dual anti-HER2 therapy - trastuzumab (8→6 mg/kg IV or 600 mg SC) and pertuzumab (840→420 mg IV), both Q3W - or, alternatively, the pertuzumab/trastuzumab SC fixed-dose combination (Phesgo; loading 1200/600 mg [15 mL], maintenance 600/600 mg [10 mL]), Q3W; all for 6 cycles.; Other Names: THP regemin
Experimental: Dose-level 2 cohort; The dose of paclitaxel oral solution is 150mg/m2.	Combination product: Paclitaxel oral solution plus Trastuzumab and Pertuzumab; Eligible patients in three cohorts receive 6 neoadjuvant THP cycles: paclitaxel oral solution at 125/150/175 mg/m² BID (D1, D8, D15), and dual anti-HER2 therapy - trastuzumab (8→6 mg/kg IV or 600 mg SC) and pertuzumab (840→420 mg IV), both Q3W - or, alternatively, the pertuzumab/trastuzumab SC fixed-dose combination (Phesgo; loading 1200/600 mg [15 mL], maintenance 600/600 mg [10 mL]), Q3W; all for 6 cycles.; Other Names: THP regemin
Experimental: Dose-level 3 cohort; The dose of paclitaxel oral solution is 175mg/m2.	Combination product: Paclitaxel oral solution plus Trastuzumab and Pertuzumab; Eligible patients in three cohorts receive 6 neoadjuvant THP cycles: paclitaxel oral solution at 125/150/175 mg/m² BID (D1, D8, D15), and dual anti-HER2 therapy - trastuzumab (8→6 mg/kg IV or 600 mg SC) and pertuzumab (840→420 mg IV), both Q3W - or, alternatively, the pertuzumab/trastuzumab SC fixed-dose combination (Phesgo; loading 1200/600 mg [15 mL], maintenance 600/600 mg [10 mL]), Q3W; all for 6 cycles.; Other Names: THP regemin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose(MTD)	The incidence of dose-limiting toxicitys and any AEs will be assessed. After the trial is completed, the MTD is determined with all the data based on isotonic regression by the shiny app "BF-BOIN" available at http://www.trialdesign.org.	Up to 24 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
total Pathological Complete Response(tpCR)	It refers to the absence of any invasive cancer in the resected specimens (breast + axilla) after completion of neoadjuvant chemotherapy and surgery (i.e., ypT0/is, ypN0).	Up to six months.
Overall Response Rate(ORR)	Response Evaluation Criteria in Solid Tumors (RECIST)：Progressive Disease (PD); Partial Response (PR); Complete Response (CR); Stable Disease (SD) Objective response rate (ORR), defined as the proportion of patients with a complete response (CR) partial response (PR) to treatment.	Up to 24 weeks.

Collaborators and Investigators

• Sponsor: Liu Shu

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2026
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 30, 2029

Study Registration Dates

• First Submitted: July 28, 2026
• First Submitted That Met QC Criteria: July 28, 2026
• First Posted (Actual): July 31, 2026

Study Record Updates

• Last Update Posted (Actual): August 4, 2026
• Last Update Submitted That Met QC Criteria: August 3, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Breast cancer; Neoadjuvant Therapy; HER2 positive; Oral paclitaxel; BF-BOIN
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Diterpenes; Trastuzumab; Paclitaxel; pertuzumab
• Other Study ID Numbers: OT-2025-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No