An Open-Label, Bayesian Adaptive Phase II Clinical Study in HR+/HER2- Advanced Breast Cancer After Progression on Standard Therapy

Overview

This is a prospective, Phase II, open-label, two-arm parallel study evaluating the efficacy and safety of combined treatment (L-Ornithine L-Aspartate, N-Acetylcysteine) with CDK4/6 inhibitors and Fulvestrant in patients with HR-positive/HER2-negative advanced breast cancer (ABC) who have progressed on prior standard therapy including CDK4/6 inhibitors and endocrine therapy.

Interventions

• Drug L-Ornithine L-Aspartate
  3g orally three times daily
• Drug CDK4/6 inhibitor
  at the physician's choice
• Drug Fulvestrant
  500mg IM on Days 1 \& 15 of Cycle 1, then Day 1 of subsequent cycles
• Drug N-Acetylcysteine (NAC) Treatment
  600mg orally twice daily
• Drug Pioglitazone (PIO)
  30mg orally once daily
• Drug PARP inhibitor
  at the physician's choice

Primary outcome measures

• Objective Response Rate (ORR) [Time frame: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months]

Secondary outcome measures (4)

• Disease Control Rate (DCR) [Time frame: Baseline through end of study, assessed up to 6 months]
• Progression Free Survival (PFS) [Time frame: Randomization to death from any cause, through the end of study, assessed up to 6 months]
• Safety and treatment-related AEs (assessed by CTCAE v5.0) [Time frame: Randomization to death from any cause, through the end of study, assessed up to 12 months]
• Biomarker analysis [Time frame: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months]

Eligibility criteria

Inclusion criteria

• Women aged ≥ 18 years old.
• Patients with histologically confirmed HR+/HER2- invasive breast cancer (specific definition: ER > 10% tumor cell positivity by immunohistochemistry is defined as ER positive, PR positive, PR > 10% tumor cell positivity is defined as PR positive; HER2 0 - 1+ or HER2 ++ but negative by FISH without amplification is defined as HER2 negative).
• Patients with HR+/HER2- advanced breast cancer who have experienced disease progression after receiving systemic therapy including CDK4/6 inhibitors and endocrine therapy.
• Patients whom the investigator judges to be suitable for continued endocrine therapy
• Patients with at least one measurable lesion per RECIST version 1.1 criteria (≥ 20 mm on conventional CT scan, ≥ 10 mm on spiral CT scan, and without prior radiotherapy for measurable lesion).
• Patients whose main organs function normally by meeting the following requirements:
• Hematology criteria: HB ≥ 90 g/L (no blood transfusion within 14 days); ANC ≥ 1.5 × 109/L; PLT ≥ 75 × 109/L;
• Blood chemistry criteria: TBIL ≤ 1.5 × ULN (upper limit of normal); ALT and AST ≤ 3 × ULN; if liver metastasis is present, then ALT and AST ≤ 5 × ULN; serum Cr ≤ 1× ULN, endogenous creatinine clearance > 50 mL/min (Cockcroft-Gault formula);
• Patients who have not received radiotherapy, molecular targeted therapy, or surgery within 3 weeks prior to the start of the study and have recovered from acute toxicities of prior therapies (if a surgery has been undergone, the wound has completely healed); patients who have no peripheral neuropathy or Grade I peripheral neurotoxicity;
• Patients with ECOG score ≤ 2, and life expectancy ≥ 3 months;
• Female subjects of childbearing potential are required to use a medically acceptable method of contraception during study treatment and for at least 3 months after the last dose of study drug;
• Subjects will be enrolled in this study voluntarily, sign the informed consent form (ICF), have good compliance, and cooperate with follow-up.

Exclusion criteria

• Patients who have received radiotherapy (except for palliative reasons), chemotherapy, immunotherapy, or bisphosphonates (except for bone metastases) within 3 weeks prior to treatment.
• Patients with uncontrolled central nervous system metastases (defined as symptomatic or requiring the use of corticosteroids or mannitol to control symptoms).
• Patients with a history of clinically important or uncontrolled heart disease, including congestive heart failure, angina pectoris, myocardial infarction within the past 6 months, or ventricular arrhythmia.
• Patients with ongoing ARs ≥ Grade 1 due to prior therapy. Exception to this is alopecia or those that, in the opinion of the investigator, should not be excluded. Such cases should be clearly documented in the investigator's notes.
• Patients who have undergone major surgery (except for minor outpatient surgery, such as placement of vascular access) within 3 weeks of the first course of study treatment.
• Pregnant or lactating patients.
• Patients with a history of malignancy (except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) within the past five years.
• Inability to swallow, chronic diarrhea and intestinal obstruction, there are multiple factors affecting the taking and absorption of drugs.
• Presence of a third space effusion (such as large pleural fluid and ascites) that cannot be controlled by drainage or other methods.
• Long-term unhealed wounds or incompletely healed fractures.
• Patients with known HBV or HCV infection active phase or hepatitis B DNA ≥ 500, or chronic phase with abnormal liver function.
• Those with allergies, or those who are known to have a history of allergy to the drug components of this study.
• For the Experimental: PARP inhibitor + Fulvestrant + Pioglitazone arm , patients with pathogenic germline BRCA1/2 mutations.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan University Shanghai Cancer Center — Shanghai

Identifiers

NCT: NCT07117630 · SCHBCC-N096

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗