A Pilot Study of a Micro-Organosphere Drug Screen Platform to Lead Care in Advanced Breast Cancer

The purpose of this study is to assess the feasibility of generating patient derived micro-organospheres (PDMO) from patients with advanced breast cancer to determine sensitivity to the most common forms of chemotherapy used in advanced breast cancer care.

Study Overview

• Status: Terminated
• Conditions: Advanced Breast Cancer
• Intervention / Treatment: Procedure: Breast Cancer Tumor Resection

Detailed Description

The purpose of this study is to determine the feasibility of generating sufficient patient derived micro-organospheres (PDMO) from a biopsy of a patient's advanced breast cancer to determine sensitivity to the most common forms of chemotherapy used in advanced breast cancer care. While subjects are on study, they will first receive 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. This study aims to enroll 15 patients. Of this 15 patient cohort we aim to enroll 5 patients with estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) disease, 5 patients with ER+/HER2+ or ER-/HER2+ disease, and 5 patients with ER-/HER2- (TNBC) disease. There are risks to having biopsies and blood draws that may include moderate bleeding and pain at the biopsy site.

• Study Type: Observational
• Enrollment (Actual): 7

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Subjects with advanced breast cancer

Description

Inclusion Criteria:

1. Provide written informed consent.
2. Female ages 18 or older.
3. Have measurable disease ≥ 2 cm defined by RECIST version 1.1.
4. 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.
5. 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.

6. 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
7. 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.
8. Impending visceral crisis is allowed only if the patient can have a biopsy prior to starting systemic mono-chemotherapy
9. ECOG performance status of 0, 1, or 2.
10. 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:

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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 Outcome Measures

Outcome Measure	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.	End of study (up to 2 years)

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Susan Dent, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2022
• Primary Completion (Actual): May 7, 2024
• Study Completion (Actual): May 7, 2024

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: November 30, 2020
• First Posted (Actual): December 7, 2020

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Advanced Breast Cancer; Chemotherapy; Patient derived micro-organospheres (PDMO)
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: Pro00107118

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No