Clinical trial NCT06155305: Organoids Based Drug Sensitivity in Neoadjuvant Chemotherapy of Breast Cancer
Official title: Consistency of Organoids Based Drug Sensitivity and Efficacy of Neoadjuvant Chemotherapy in Breast Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Organoids
Breast Cancer
Neoadjuvant Chemotherapy
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2023-12-04
Enrollment: 58
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with breast cancer (AJCC stages I to IIIA) who need to receive neoadjuvant therapy.

Brief summary: Breast cancer is the most common malignancy in women worldwide. Patients with breast cancer are often diagnosed at later stages and have a strong desire for breast conservation, necessitating neoadjuvant chemotherapy. Tumors of different molecular subtypes and individual variations among patients lead to significant differences in treatment efficacy. Precise assessment of patients' responses to treatment regimens is imperative in advancing prognosis of breast cancer. In this study, 58 patients diagnosed with breast cancer and scheduled for neoadjuvant therapy will be recruited. Patient-derived organoids from their tumor biopsies will be utilized to evaluate the sensitivity of chemotherapy regimen. These drugs primarily include Doxorubicin, Carboplatin, Cyclophosphamide, Paclitaxel, as well as targeted therapies such as Herceptin and Pertuzumab.

Detailed description: 58 early-stage breast cancer patients scheduled to undergo neoadjuvant therapy will be recruited. Baseline information including medical history, ultrasound, Breast-Specific Gamma Imaging (BSGI), and magnetic resonance imaging (MRI) records, will be collected both before and after two cycles of chemotherapy. Tumor tissue from these patients will be obtained via biopsies guided by ultrasound. Patient-derived organoids (PDOs) will be established and cultured from the collected tumor tissue. Subsequently, these PDOs will be subjected to treatment with drugs from standard chemotherapeutic regimens for breast cancer. The growth of the organoids will be assessed post-treatment, and dose-response curves will be generated. For evaluating the clinical outcomes of the patients, the Residual Cancer Burden (RCB) system will be used to evaluate tumor histological responses in patients. The consistency between treatment responses observed in the PDO models and the clinical outcomes of patients will be evaluated through correlation analysis.

Eligibility criteria: Inclusion Criteria:

1. Signed informed consent form and willingness to participate in the clinical study.
2. Female patients aged between 18 and 70 years old.
3. Confirmed early-stage breast cancer eligible for surgery (AJCC stages I to IIIA), with a tumor diameter of ≥ 2cm detected by MRI and without distant metastasis (M0).

   The largest lesion among multiple lesions has a diameter of ≥ 2cm.
4. ECOG performance status score of 0-1.
5. No significant abnormalities in liver and kidney function (BIL \<1.5-fold upper limit of normal (ULN)；ALT\<2.5×ULN; AST\<2.5×ULN；Crea≤1×ULN).

Exclusion Criteria:

1. Received prior treatments.
2. Locally advanced breast cancer not amenable to surgery or inflammatory breast cancer (AJCC stage unresectable III).
3. Bilateral breast cancer.
4. Multiple breast cancers distributed in different quadrants.
5. Patients not suitable for neoadjuvant chemotherapy.

Primary outcomes:
measure: Correlation between drug sensitivity test results in patient-derived organoid models and clinical outcomes.
timeFrame: 2023.12-2025.06
Secondary outcomes:
measure: Comparison between drug sensitivity of organoid models and clinical imaging (MRI, ultrasound, BSGI) in predicting the efficacy of neoadjuvant chemotherapy.
timeFrame: 2023.12-2025.06
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: 2 nd Affiliated Hospital, School of Medicine, Zhejiang University, China
state: Zhejiang
Study officials:
affiliation: 2 nd Affiliated Hospital, School of Medicine, Zhejiang University, China
name: Jian Huang
role: PRINCIPAL_INVESTIGATOR
affiliation: 2 nd Affiliated Hospital, School of Medicine, Zhejiang University, China
name: Zhigang Chen
role: PRINCIPAL_INVESTIGATOR
References: