Patient Derived Organoid-guided Personalized Treatment Versus Treatment of Physician's Choice in Breast Cancer

NCT06268652 | Recruiting Phase 3

• 1 other identifier: B2023-686-01
• Study Type: interventional
• Target: 302
• Locations: 1 country
• Sites: 1

Brief Summary

This multicenter, open-label, randomized phase III trial is designed to study the efficacy and safety of organoid-guided personalized treatment （OGPT）versus treatment of physician's choice (TPC) in previously treated refractory breast cancer.

Conditions

Breast Cancer; Refractory Breast Carcinoma

Keywords

breast cancer; TPC; patient derived organoid; PDO

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Progression-free survival (PFS) is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic progressive disease (PD) or death due to any cause.

  Within approximately 48 months

Secondary Outcomes (5)

• Overall Survival (OS)

  Within approximately 48 months

• Objective Response Rate (ORR)

  Within approximately 48 months

• Duration of Response (DOR)

  Within approximately 48 months

• Disease Control Rate (DCR)

  Within approximately 48 months

• Incidence of Treatment-related Adverse Events

  Within approximately 48 months

Study Arms (2)

Organoid-guided personalized treatment

EXPERIMENTAL

Subjects randomly assigned to OGPT need to provide sufficient tissue for organoid culture. After successful organoid culture, drug screening will be performed, and they will be treated with drugs predicted to be sensitive by PDO drug susceptibility screening.

Other: Organoid-guided personalized treatment

Treatment of physician's choice

ACTIVE COMPARATOR

Subjects in the TPC arm will receive treatment with one of the following regimens selected by the physician following NCCN guidelines: capecitabine, gemcitabine, vinorelbine, and eribulin. If it is HER2-positive, anti-HER2 therapy can be combined with it, except for ADC drugs.

Drug: Gemcitabine; Drug: Capecitabine; Drug: Vinorelbine; Drug: Eribulin

Interventions

Organoid-guided personalized treatment OTHER

After the organoid culture is successful, the personalized drug library customized by our team will be used for screening. Sensitive drugs are selected based on the results of drug screening, and the most appropriate personalized treatment plan is selected based on NCCN guideline recommendations, drug safety, and conventional drugs used in the treatment of breast cancer. The personalized drug library customized by our team contains 55 drugs approved by the FDA. For specific usage, dosage and time intervals, please refer to the instructions of the corresponding drug.

Also known as: OGPT

Organoid-guided personalized treatment

Gemcitabine DRUG

1000mg/m2，IV, days 1, 8, q3w

Also known as: Gemzar

Treatment of physician's choice

Capecitabine DRUG

1000mg/m² , PO, bid, days1-14, q3w

Also known as: Xeloda

Treatment of physician's choice

Vinorelbine DRUG

25mg/m2, IV or 60mg/m² (oral), days 1 and 8, q3w

Also known as: Navelbine

Treatment of physician's choice

Eribulin DRUG

1.4mg/m², IV, days 1 and 8, q3w

Also known as: Halaven

Treatment of physician's choice

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily participate and sign the informed consent form
• Aged over 18 years old, regardless of gender;
• Locally advanced or metastatic breast cancer confirmed by histopathology;
• Received ≥2 previous lines of anti-tumor treatment and developed resistance to standard treatment;
• Life expectancy ≥3 months;
• ECOG performance status 0 to 2;
• Have measurable or/and evaluable lesions (non-radiotherapy target areas) (lesion evaluation is based on Recist1.1 standards);
• No serious organ (main organ: heart, lung, liver, kidney) functional abnormalities (refer to respective standards);
• Routine blood test: white blood cells (WBC) ≥3 × 109/L; absolute neutrophil count (ANC) ≥1.5 × 109/L; platelets (PLT) ≥100 × 109/L; hemoglobin (Hgb) ≥8g /dL;
• Blood biochemical indicators: AST (SGOT), ALT (SGPT) ≤ 2.5 × upper limit of normal value (ULN) (in the case of no liver invasion) or ≤ 5 × upper limit of normal value (ULN) (in the case of liver invasion) Bottom); total bilirubin (TBIL) ≤ ULN; serum creatinine clearance calculated according to the CG formula \> 30 mL/min
• Coagulation function: prothrombin time (PT), international normalized ratio (INR) ≤ 1.5 × ULN (unless warfarin is being used for anticoagulation);
• Able to comply with the research visit plan and other program requirements;
• All patients of childbearing age must agree to take effective contraceptive measures during the study and within 6 months of stopping treatment. Female patients of childbearing age must have a negative urine pregnancy test before treatment.
• Subjects must meet all of the following additional criteria to be included in the OGPT group:
• No absolute contraindications to tissue-invasive procedures required to obtain organoid cultures。

You may not qualify if:

• The medical history and comorbidities are as follows:
• The patient is participating in other interventional clinical studies or the end of treatment in the previous clinical study is less than 4 weeks;（2）Those who have been treated less than 4 weeks since the last anti-tumor treatment (radiotherapy, chemotherapy, targeted therapy, immunotherapy or local-regional treatment); the adverse reactions related to anti-tumor treatment (except alopecia) after previous systemic anti-tumor treatment have not returned to NCI- Patients with CTC AE ≤ grade 1;
• Other active malignant tumors that require simultaneous treatment;
• Known history of organ transplantation and allogeneic hematopoietic stem cell transplantation;
• For subjects who have undergone major surgery or severe trauma, the effects of the surgery or trauma have been eliminated for less than 14 days before enrollment;
• Patients with active pulmonary tuberculosis need to be excluded. Patients suspected of having active pulmonary tuberculosis should have chest X-rays, sputum, and clinical symptoms and signs to rule out the disease. Patients with a history of active pulmonary tuberculosis infection within the previous year must be excluded, even if they have been treated; patients with a history of active pulmonary tuberculosis infection more than 1 year ago must also be excluded, unless it is proven that the course and type of anti-tuberculosis treatment previously used are satisfactory. appropriate;
• Severe acute or chronic infection requiring systemic treatment
• Suffering from heart failure (New York Heart Association Class III or IV) and despite receiving appropriate medical treatment, poorly controlled coronary artery disease or arrhythmia, or a history of myocardial infarction within 6 months before screening patient.
• Pregnant or lactating women.
• No anti-tumor treatment is planned.
• Known to have a positive history of human immunodeficiency virus (HIV) test or known to have acquired immunodeficiency syndrome (AIDS);
• Untreated active hepatitis (hepatitis B: HBsAg positive and HBV DNA ≥ 500IU/mL; hepatitis C: HCV RNA positive and abnormal liver function); combined with hepatitis B and hepatitis C co-infection;
• Hypersensitivity to any study drug;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Yanxia Shi

Guangzhou, None Selected, 510060, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Gemcitabine; Capecitabine; Vinorelbine; eribulin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Yanxia Shi

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanxia Shi

CONTACT

020-87343368; shiyx@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Professor

Study Record Dates

• First Submitted: January 23, 2024
• First Posted: February 20, 2024
• Study Start: January 15, 2024
• Primary Completion: February 15, 2026
• Study Completion (Estimated): January 15, 2028
• Last Updated: February 20, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)