Using a new platform to personalize breast cancer treatment with patient-derived organoids

Quadratic Phenotypic Optimisation Platform (QPOP) Utilisation to Enhance Selection of Patient Therapy Through Patient Derived Organoids in Breast Cancer

This study is testing a new method to help doctors choose the best personalized drug combinations for people with advanced breast cancer by using tiny lab-grown versions of their tumors.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 26 (estimated)
• Ages: 21 Years to 99 Years
• Sex: Female
• Sponsor: National University Hospital, Singapore (Academic / other)
• Drugs / interventions: trastuzumab, chemotherapy, immunotherapy, lapatinib, lenvatinib
• Locations: 1 site (Singapore)
• Trial ID: NCT05177432 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the feasibility of the Quadratic Phenotypic Optimisation Platform (QPOP) as a clinical decision support tool for selecting personalized drug combinations for patients with advanced breast cancer. The study aims to utilize patient-derived organoids to better reflect the heterogeneity of breast cancer and improve treatment outcomes. By focusing on patients with confirmed breast carcinoma, the trial seeks to optimize therapy selection based on individual tumor characteristics. The approach is designed to address the limitations of traditional two-dimensional cell cultures and enhance the relevance of preclinical models in drug development.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 21 and older with histologically confirmed breast carcinoma who have experienced disease progression after at least one line of palliative systemic therapy.

Not a fit: Patients with early-stage breast cancer or those who have not received prior systemic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to more effective and personalized treatment options for patients with advanced breast cancer.

How similar studies have performed: While the use of patient-derived organoids is a relatively novel approach, preliminary studies have shown promise in utilizing similar methodologies for other cancer types.

Eligibility criteria

Part A - Inclusion and exclusion criteria to be fulfilled both prior to study enrolment and prior to commencement of study drug

Inclusion Criteria:

* Age \>= 21 years.
* Histological confirmed breast carcinoma of any subtype (any estrogen receptor, progesterone receptor and HER2 receptor status)
* ECOG 0-1.
* At least 1 tumour lesion (primary or metastatic) amenable to fresh biopsy
* At least 1 measurable tumour lesions based on RECIST 1.1 criteria
* Estimated life expectancy of at least 12 weeks.
* Has documented progressive disease from last line of therapy.
* Has received at least 1 line of palliative systemic therapy
* Expected adequate organ function (bone marrow, hepatic, renal) after recovering from treatment-induced acute toxicities at the time of study treatment.
* Signed informed consent from patient or legal representative.
* Able to comply with study-related procedures.

Exclusion Criteria:

Patients will be excluded from the study for any of the following reasons:

* Pregnancy.
* Breast feeding.
* Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
* Active bleeding disorder or bleeding site.
* Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
* History of significant neurological or mental disorder, including seizures or dementia.

Part B - Additional inclusion and exclusion criteria to be fulfilled prior to commencement of study drug

Inclusion criteria

Patients may be included in the study only if they meet all of the following criteria:

• Adequate organ function including the following:

Bone marrow:

* Absolute neutrophil (segmented and bands) count (ANC) \>= 1.5 x 109/L
* Platelets \>= 100 x 109/L
* Hemoglobin \>= 8 x 109/L

Hepatic:

* Bilirubin \<= 1.5 x upper limit of normal (ULN),
* ALT or AST \<= 2.5x ULN, (or \<=5 X with liver metastases)

Renal:

- Creatinine \<= 1.5x ULN

Exclusion criteria

Patients will be excluded from the study for any of the following reasons:

* Treatment within the last 30 days with any investigational drug.
* Concurrent administration of any other tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy at time of commencement of study drug.
* Major surgery within 28 days of study drug administration.
* Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
* Non-healing wound.
* Poorly controlled diabetes mellitus.
* Symptomatic brain metastasis.
* Contraindication to receiving specific QPOP-directed study treatment within drug that has been recommended based on QPOP analyses (e.g., poorly controlled diabetes mellitus for alpelisib, left ventricular ejection fraction of \<50% for trastuzumab-emtansine)
* Received more than 2 lines of empirical therapy between tumor biopsy for organoids growth and commencement on QPOP-directed study treatment (including endocrine therapy, chemotherapy, targeted therapy or immunotherapy)
* Biopsy for organoids growth performed more than 12 months from time of study drug commencement
* Has not recovered from acute toxicities from prior anti-cancer therapy

Where this trial is running

Singapore

• National University Hospital Singapore — Singapore, Singapore (Recruiting)

Study contacts

• Study coordinator: Soo Chin Lee

Conditions Breast Cancer; QPOP; Enhance Selection; Patient Therapy; Patient Derived Organoids