A Pilot Study of a Micro-Organosphere Drug Screen Platfor... | NCT04655573

NCT04655573

Protocol Section

Identification Module

Results Section

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Annotation Section

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Document Section

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Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Patient Derived Micro-Organospheres (PDMO)		Subjects will undergo image-guided biopsy as a standard of care clinical biopsy from which extra tissue is taken for research purposes. Following the biopsy, a PDMO will be generated and they will receive a chemotherapy regimen as determined by their treating physician. PDMO are successfully generated, and the patient begins treatment with a hemotherapy backbone. A patient will be considered evaluable if pathology results are available from the biopsy.	Procedure: Breast Cancer Tumor Resection

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Breast Cancer Tumor Resection	Procedure	Patients with ABC will be receiving a biopsy, and a PDMO from the patient's biopsies will be generated from it. It is a model correlating clinical response with PDMO sensitivity to the most common forms of chemotherapy used in advanced breast cancer care.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
The proportion of patients with successful generation of PDMO from the patient's biopsy	The PDMO establishment will be monitored and success will be defined as the formation of 3D organoid structures in at least 80% of droplets in each well, in 20 randomly sampled wells per PDMO model, within 7 days. With an anticipated generation of 90% we anticipate being able to generate 13 PDMO from the first 15 patients to perform a drug screen within 10 days of biopsy. The exact 90% lower confidence bound (LCB) will be computed for the proportion of patients with successful generation of PDMO and completed drug screen within 10 days. For the first 6 patients, if at least 5 PDMO can be generated and screened on 6 patients' samples the procedure will be deemed feasible. With 6 patients studied the exact 90% LCB assuming 5 successful cases is 0.71. We would thus be 90% confident that the success rate of this strategy is at least 71%.	10 days of biopsy

Secondary Outcomes

Measure	Description	Time Frame
Association between specific chemotherapy sensitivity in PDMO to clinical outcome of patient	For the 15 evaluable patients, the MODEL ABC platform will be used to assess sensitivity to chemotherapy and generate a prediction model for correlation with patient data. For each sample, two primary outcomes will be collected: i) PDMO drug sensitivity data, and ii) the patient's clinical outcome (PFS). Treating PDMO with 10 chemotherapy single agents at 10 drug concentrations each will generate drug sensitivity data. For all 15 samples, PDMO sensitivity to each concentration of each drug will be used alongside the 15 clinical responses (PFS) to develop a predictor of PFS by correlating drug response data to clinical data.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Provide written informed consent.
Female ages 18 or older.
Have measurable disease ≥ 2 cm defined by RECIST version 1.1.
Amenable to standard of care biopsy with co-consent to the Duke BioRepository & Precision Pathology Center (BRPC) protocol (Pro00035974) to collect extra biopsy tissue for research or willing to provide extra tissue other than standard of care without co-consent to BRPC.
Evidence of advanced cancer of the breast that is surgically unresectable with pathology confirming ER, PR, and HER2 status. NOTE: patients may enroll prior to receiving clinical biopsy results based on historical pathology results.
Patient is eligible for chemotherapy as monotherapy or in combination with single-agent anti HER2 Therapy.
- ER+/PR+/HER2-, must have progressed or be intolerant to CDK 4/6 inhibitor and/or endocrine therapy unless CDK 4/6 inhibitor is not able to be provided per the clinician's discretion endocrine therapy and CDK 4/6 inhibitor
- ER+/PR+/HER2+ or ER-/PR-HER2+, must have progressed or be intolerant to ≥ 2 lines of anti-HER2 therapy and be considered for mono-chemotherapy with trastuzumab and/or anti-HER2 tyrosine kinase inhibitor
- ER-/PR-HER2-, PD-L1- and/or TMB <10 may may be considered for first line of treatment
Treating physician is planning to treat breast cancer in the advanced setting with a chemotherapy backbone. This study excludes patients who will receive an antibody-drug conjugate as their proposed treatment.
Impending visceral crisis is allowed only if the patient can have a biopsy prior to starting systemic mono-chemotherapy
ECOG performance status of 0, 1, or 2.
Any metastatic site that is ≥ 2cm and amenable to core needle biopsy. Patients with brain metastases are allowed and MOS may be generated from a resected breast cancer brain metastasis

Exclusion Criteria:

Actively requiring systemic antibiotics.
Clinically significant cardiac disease, including unstable angina or acute myocardial infarction within 6 months of enrollment.
Leptomeningeal disease
Pregnant women.
Enrolling on an investigational agent.