NCT06102824

Organoid-based Functional Precision Therapy for Advanced Breast Cancer

Organoid-Guided Functional Precision Therapy Versus Treatment of Physician's Choice in Previously Treated HER2-negative Advanced Breast Cancer: A Phase II, Multicenter, Open-label, Randomized Controlled Trial

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 252 (estimated)
• Sponsor: Guangdong Provincial People's Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

This is a phase II, multicenter, open-label, randomized controlled trial to compare the efficacy of organoid-guided treatment (OGT) to treatment of physician's choice (TPC) in previously treated, HER2-negative locally advanced or metastatic breast cancer. The study will seek to provide evidence for utilizing patient-derived organoid (PDO) model to personalize treatment strategies and inform clinical care for advanced breast cancer. Subjects randomized to the OGT group will undergo PDO generation and receive treatment dictated by subsequent PDO drug sensitivity screening. Subjects randomized to the TPC group will receive empirical therapy as selected by the treating physician.

Detailed description

Treatment for advanced-stage breast cancer has long been challenging. Genomic-based precision medicine was able to facilitate treatment selection in some patients, but there were considerable instances where genomic profiling failed to assign effective interventions or patients exhibited refractoriness to the drugs nominated by genomic alterations. Patient-derived organoids (PDOs) represent a tractable tool that may compensate for the drawbacks of genomic medicine to identify therapeutic opportunities in rare or metastatic cancers. Previous research has demonstrated that PDOs displayed strong biological fidelity to their original tumors and functional precision medicine based on PDO drug screening could confer survival benefits in breast cancer patients. This multicenter, open-label, randomized phase II trial aims to investigate the safety and efficacy of organoid-guided treatment (OGT) versus treatment of physician's choice (TPC) in previously treated, HER2-negative locally advanced or metastatic breast cancer. Randomization will be stratified by hormone receptor status and prior chemotherapy for the advanced or metastatic disease. Subjects in the OGT group will receive treatment predicted to be the most efficacious by the PDO drug sensitivity screening, and subjects in the TPC group will receive treatment selected by the treating physician. Treatments tested in PDO drug screening or chosen by the treating physician will be guided by NCCN guidelines. Treatment that subjects have previously received before randomization is no longer subjected to PDO sensitivity screening. This study will provide valuable evidence on the real-time application of PDOs in the context of clinical care.

Conditions

• HER2-negative Breast Cancer
• Advanced Breast Cancer

Interventions

Type	Name	Description
DRUG	Organoid-guided treatment	The drugs predicted to be the most sensitive through organoid drug sensitivity screening. The drugs selected for sensitivity screening are from the following options: taxane, anthracycline, 5-fluorouracil, gemcitabine, vinorelbine, eribulin, utidelone, carboplatin, sacituzumab govitecan, and trastuzumab deruxtecan (for HER2-low patients).
DRUG	Taxane	Albumin-bound paclitaxel 260mg/m2, IV, q3w, or 100-125mg/m2, IV, days 1, 8, and 15, q4w OR Liposomal paclitaxel 175mg/m2, IV, q3w
DRUG	Capecitabine	1000-1250mg/m2, PO, bid, days1-14, q3w
DRUG	Gemcitabine	800-1200mg/m2, IV, days 1, 8, q3w
DRUG	Vinorelbine	20-35mg/m2, IV, days 1 and 8, q3w
DRUG	Eribulin	1.4mg/m2, IV, days 1 and 8, q3w
DRUG	Anthracycline	Liposomal doxorubicin 50mg/m2, IV, q3w OR Liposomal doxorubicin 40mg/m2+Cyclophosphamide 600mg/m2, IV, q3w
DRUG	Carboplatin	Carboplatin AUC 6, IV, q3w or q4w OR Carboplatin AUC 2+Gemcitabine 1000mg/m2, IV, days 1 and 8, q3w OR Carboplatin AUC 2+Albumin-bound paclitaxel 125mg/m2, IV, days 1 and 8, q3w
DRUG	Utidelone	30mg/m2, IV, once per day on days 1-5, q3w
DRUG	Trastuzumab deruxtecan	5.4mg/kg, IV, q3w
DRUG	Sacituzumab govitecan	10mg/kg, IV, days 1 and 8, q3w

Timeline

• Start date: 2024-10-01
• Primary completion: 2027-06-30
• Completion: 2028-06-30
• First posted: 2023-10-26
• Last updated: 2024-11-25

Locations

1 site across 1 country: China