KM3D Multicenter Cancer Consortium: Predicting Patient Response Using 3D Cell Culture Models

KM3D Multicenter Cancer Consortium Study: Validation of In Vitro 3D Cell Culture Models for Tumor Drug Sensitivity After Tissue Removal

This study will assess the ability of the Known Medicine platform to predict the efficacy of certain cancer drug treatments and to validate that tumor organoid drug sensitivity is representative of patient treatment outcomes.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Effects of Chemotherapy; Predictive Cancer Model
• Intervention / Treatment: Diagnostic test: Known 3Dx Test

Detailed Description

This is a non-interventional clinical study in which (1) cancer tissue that has been resected, biopsied, or drained due to malignant pleural effusion and that is left remaining after (or is not being used during) a pathology investigation and, where possible, (2) a vial of the same patient's blood is sent to Known Medicine Inc. for placement into organoids and subsequent tumor drug sensitivity measurement.

Patients will be consented prior to performance of a medically indicated and pre-planned surgical procedure during which at least a 1cm3 piece of tumor tissue or >100 mL pleural effusion fluid and blood in a separate vial are obtained. These samples will be sent after removal to Known Medicine Inc. from the hospital using a kit provided by Known Medicine. Within the Known Medicine provided kit a data form, freezer pack and containers for the specimens will be provided.

If a solid tissue sample, the tissue will be washed and subsequently digested into a single cell solution using enzymatic digestion methods. Cells will be sorted into cancer and stromal cell populations, stained fluorescently with intramembrane stain, and placed into a 3D cell culture matrix within a multi-well plate. Cells may also be genetically sequenced.

If an aspirated fluid sample, cells will be separated from the fluid and further sorted into cancer cell populations.

Cultures will be allowed to sustain themselves for 48 hours, at which point standard of care chemotherapeutic or other FDA approved drug treatments will be administered. After 72 hours, control and treated wells will be imaged using fluorescence and cell phenotype will be evaluated. Media from cultures may also be evaluated. After imaging, media will be removed and a metabolic assay will be performed to determine culture viability. Using the described quantitative outcomes, tumor sensitivity to each of the administered treatments will be determined.

Patients will be followed and their response to treatment and outcome information from the hospital will be obtained which will allow retrospective validation of tumor organoid sensitivity.

• Study Type: Observational
• Enrollment (Anticipated): 2000

Contacts and Locations

• Study Contact: Name: Charlotte Waits, PhD; Phone Number: 801-953-0895; Email: clinical@knownmed.com
• Study Contact Backup: Name: Andrea Mazzocchi, PhD; Email: andrea@knownmed.com

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Janai S Reisenauer, MD; Email: reisenauer.janani@mayo.edu
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke Cancer Institute
      • Principal Investigator: Kamran Mahmood, MD
      • Contact: Kamran Mahmood, MD; Email: k.mahmood@duke.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: Horiana Grosu, MD; Email: HBGrosu@mdanderson.org
      • Principal Investigator: Horiana Grosu, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients who have primary solid cancer that is being surgically resected or biopsied and are 18 years of age or older.

Description

Inclusion Criteria:

• A demonstrated primary solid cancer for which it is medically indicated and planned to be surgically resected, biopsied, or drained (via malignant pleural effusion).
• The ability to ship the tissue sample within 24 hours of removal from the patient.
• Signed and dated consent to giving tissue as well as allowing for de-identified medical history information regarding administered treatments and treatment outcomes to be shared.
• over 18 years of age

Exclusion Criteria:

• Presence of a condition(s) or diagnosis, either physical or psychological, or physical exam finding that precludes participation in the opinion of the Investigator.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Cancer patients; Patients who have primary solid cancer that is being surgically resected, biopsied, or drained (via malignant pleural effusion) and are 18 years of age or older.

Diagnostic test: Known 3Dx Test; Cancer tissue is cultured and treated with a panel of FDA approved chemotherapy and targeted therapies at a range of doses. Cell growth and phenotypes are measured to determine which treatment or treatment combinations would yield the best results for a patient. Test results are compared to actual patient outcomes collected at 3, 6, 9, and 12 months post tissue collection to determine the predictive power of the Known 3Dx Test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug treatment response	Measurements of changes in cell population size and phenotype will be taken from cellular imaging done before and during compound or drug administration. Platform drug response is defined as a statistically significant difference between drug-treated micro-tumors grown from the patient's sample and untreated control wells.	7 days after sample receipt
Predictive of tumor response	To understand if cellular phenotypic and population changes seen in Outcome 1 are clinically relevant we will compare the statistically significant changes we see to actual patient response on that treatment. The goal is to grow a large enough data set to gain an understanding about which of the changes seen by the KM3D test are clinically relevant.	3 to 12 months post tissue collection (depending on when the physician prescribed treatment course is complete). Treatment updates will be given at 3, 6, 9, and 12 months but only the final reported result will be used for comparison.

Collaborators and Investigators

• Sponsor: Known Medicine, Inc.
• Collaborators: M.D. Anderson Cancer Center; Mayo Clinic; Duke Cancer Institute
• Investigators: Principal Investigator: Andrea Mazzocchi, PhD, Known Medicine, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2021
• Primary Completion (Anticipated): January 31, 2025
• Study Completion (Anticipated): January 31, 2026

Study Registration Dates

• First Submitted: March 29, 2022
• First Submitted That Met QC Criteria: April 18, 2022
• First Posted (Actual): April 20, 2022

Study Record Updates

• Last Update Posted (Actual): April 24, 2023
• Last Update Submitted That Met QC Criteria: April 21, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: KM-20-001

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: Yes
• product manufactured in and exported from the U.S.: No