Clinical Performance Evaluation of the C2i-Test

Clinical Performance Evaluation of the C2i-Test for Detecting Molecular Residual Disease (MRD) in Bladder Cancer Patients.

The C2i-WGS-MRD Test (hereinafter referred to as C2i-Test), a personalized molecular circulating tumor DNA (ctDNA) test, is an in vitro qualitative test that uses next generation sequencing (NGS) based whole-genome sequencing (WGS) data for detecting molecular residual disease (MRD) in patients diagnosed with muscle-invasive bladder cancer (MIBC) and histopathologically classified as stage II-IIIA. The C2i-Test is a single site assay performed in the C2i Genomics' CLIA-certified laboratory. This is a prospective non-interventional study to collect definitive evidence of the safety and effectiveness of C2i-Test for the intended use, in a statistically justified number of subjects.

Study Overview

• Status: Terminated
• Conditions: Muscle-Invasive Bladder Carcinoma
• Intervention / Treatment: Diagnostic test: C2i Test

• Study Type: Observational
• Enrollment (Actual): 3

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Bloomfield, New Jersey, United States, 07003
      • New Jersey Urology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with clinically and pathologically confirmed diagnosis of MIBC stage II-IIIA, planned to undergo RC.

Description

Inclusion Criteria:

• Participants must have clinically and pathologically confirmed diagnosis of MIBC.
• A representative FFPE biopsy specimen (from the transurethral resection of bladder tumor - TURBT) with at least 1 H&E slide and 9 unstained slides, with an associated pathology report must be available.
• Subjects must agree to 8mL blood collection during all visits.
• Participants with MIBC, clinical stage II (cT2, N0) or IIIA (cT3, N0; cT4a, N0; cT1-T4a, N1) (lymph node positive if >10 mm on CT or MRI in short axis), diagnosed by work-up recommended by NCCN guidelines (including cystoscopy, abdominal/pelvic imaging that includes imaging of upper urinary tract collecting system, examination under anesthesia, TURBT, and bone imaging if clinical suspicion or symptoms of bone metastases within 4 weeks prior to enrollment, however patients can be enrolled if they are reassessed, and the localized status is reconfirmed with subsequent imaging studies).
• Histopathologically confirmed urothelial carcinoma as diagnosed by TURBT. Variant urothelial histology (e.g., micropapillary, plasmacytoid, sarcomatoid, nested variant, lymphoepithelioid, nested variant) is acceptable. Mixed histology (adenocarcinoma, squamous cell) is acceptable if there is a predominant (>50%) urothelial component.
• Treatment plans must include RC.
• Participant is willing and able to comply with the protocol, including RC, pelvic lymph node dissection (PLND), and prostatectomy (if applicable).
• The patient must be deemed appropriate for RC, PLND, and prostatectomy (if applicable) by his/her oncologist and/or urologist.
• Patient's treatment plan may or may not include neoadjuvant treatment and/or adjuvant treatment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
• Patient is willing and able to provide written informed consent for samples to be collected and used in this study.

Exclusion Criteria:

• Extravesical urothelial carcinoma (UC) that invades the pelvic and/or abdominal wall for bladder cancer (T4b) as evidenced by imaging.
• Evidence of UC in the urinary tract (ureters, renal pelvis, and urethra) as evidenced by work-up in accordance with NCCN guidelines (e.g., abdominal/pelvic imaging) that includes imaging of upper urinary tract collecting system).
• Clinical evidence of greater than 1 positive LN (≥ 10 mm in short axis) or metastatic bladder cancer per IV contrast-enhanced CT or MRI scan and/or PET-CT scan.
• Patients with mixed histology and <50% urothelial component as evidenced by TURBT pathology.
• Tumors that contain any neuroendocrine/small cell component as evidenced by TURBT pathology.
• Diagnosis of 3 or more synchronous cancers.
• Malignancies other than urothelial cancer within 5 years prior to study entry except those with negligible risk of metastases or death and treated with the expectation of curative outcome (such as: carcinoma in situ of the cervix, basal or squamous cell skin cancer, ductal carcinoma in situ treated surgically with curative intent, papillary thyroid carcinoma, localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse, or incidental prostate cancer [Gleason score ≤ 3 + 4 and PSA < 10 ng/mL] undergoing active surveillance and treatment naïve).
• Prior chemotherapy or immunotherapy, radiation therapy, or surgery other than TURBT for bladder cancer.
• Per physician discretion: patients with severe or uncontrolled concomitant medical, surgical, or psychiatric disease that could affect compliance with the protocol, the results of the study, or interpretation of the results.
• Individuals who cannot provide consent for their own participation will not be included.
• Sponsors employees and their family.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MIBC; Patients with clinically and pathologically confirmed diagnosis of MIBC stage II-IIIA, planned to undergo RC.	Diagnostic test: C2i Test; The C2i-Test, a personalized molecular circulating tumor DNA (ctDNA) test, is an in vitro qualitative test that uses next generation sequencing (NGS)-based whole-genome sequencing (WGS) data for detecting molecular residual disease (MRD).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall specificity of the C2i-Test	Predicting 3-year recurrence-free survival post- definitive treatment (RC/RC + adjuvant chemotherapy), compared to the GS diagnosis as determined by patient outcome (based on NCCN guidelines).	3-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall sensitivity of the C2i-Test	Predicting non-pCR following neoadjuvant treatment completion prior to RC, compared to the GS diagnosis as determined by the pathology report.	3-year

Collaborators and Investigators

• Sponsor: C2i Genomics
• Collaborators: Fox Chase Cancer Center; Baylor College of Medicine; New York University; The Cleveland Clinic; University of Southern California; Oregon Health and Science University; University of Washington; Ohio State University; University of Texas; New Jersey Urology; NY Health d/b/a New York Cancer and Blood Specialists
• Investigators: Principal Investigator: Yair Lotan, MD, UT Southwestern

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2022
• Primary Completion (Actual): July 27, 2022
• Study Completion (Actual): July 27, 2022

Study Registration Dates

• First Submitted: January 19, 2022
• First Submitted That Met QC Criteria: January 31, 2022
• First Posted (Actual): February 3, 2022

Study Record Updates

• Last Update Posted (Estimate): February 27, 2023
• Last Update Submitted That Met QC Criteria: February 23, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: CA-F01-02

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