Urine Tumor DNA Test for Lynch Syndrome

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Jussi Nikkola

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Tampere University Hospital

Disqualifiers: Concurrent urothelial carcinoma

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Lynch syndrome (LS) is an inherited cancer predisposition syndrome caused by pathogenic germline variants in DNA mismatch repair (MMR) genes. New cancer screening and diagnostic tools are urgently needed to identify LS-related cancers early enough for curative treatment. Urothelial cancers (comprising bladder and upper tract urothelial tumors) are the third most common cancer after colorectal and endometrial cancers in individuals with LS. Up to one in four LS individuals will develop urothelial cancer during their lifetime, with the risk varying based on the defective MMR gene. In this clinical trial, we will employ urine tumor DNA (utDNA) to identify asymptomatic urothelial cancers in Lynch syndrome patients, and to investigate the potential benefits of urine tumor DNA based screening in this high-risk population.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment for Urothelial cancer screening using urine tumor DNA test?

Research shows that a test called UroSEEK, which analyzes DNA from urine, detected 95% of bladder cancer cases when combined with urine cytology. This suggests that using DNA tests on urine can be a powerful tool for detecting urothelial cancer, especially in patients with Lynch syndrome. ^{1 2 3 4 5}

How is the Urine Tumor DNA Test treatment different from other treatments for Lynch Syndrome-related urothelial cancer?

The Urine Tumor DNA Test is unique because it uses a non-invasive method to detect genetic mutations in urine, making it easier and less uncomfortable for patients compared to traditional invasive procedures. This approach allows for early detection and monitoring of urothelial cancer in patients with Lynch Syndrome by analyzing DNA shed into the urine. ^{1 2 3 6 7}

Eligibility Criteria

This trial is for individuals with Lynch Syndrome, a genetic condition that increases cancer risk. It's focused on detecting urothelial cancers early, which include bladder and upper urinary tract tumors. Participants should have this inherited syndrome but no current symptoms of urothelial cancer.

Inclusion Criteria

I am between 50 and 75 years old.

Willing and able to provide informed consent

I have been diagnosed with Lynch syndrome.

Exclusion Criteria

I have urothelial carcinoma.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Screening Arm

Invitation to participate in urothelial cancer screening and questionnaires

1 year

Multiple visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after screening

10 years

Regular follow-up visits at 2, 5, and 10 years

Treatment Details

Interventions

• Urothelial cancer screening using urine cytology (Cancer Screening)
• Urothelial cancer screening using urine tumor DNA test (Cancer Screening)

Trial Overview The study is testing the effectiveness of a new urine tumor DNA test to screen for urothelial cancer in people with Lynch Syndrome. This will be compared to the standard urine cytology method to see if it can better detect cancer early.

Participant Groups

Group I: Screening arm Experimental Treatment 2 Interventions

Invitation to participate in urothelial cancer screening and questionnaires

Urothelial cancer screening using urine tumor DNA test is already approved in European Union, United States for the following indications:

🇪🇺 Approved in European Union as Urine Tumor DNA Test for:

• Screening for urothelial cancers in individuals with Lynch Syndrome

🇺🇸 Approved in United States as Urine Tumor DNA Test for:

• Screening for urothelial cancers in individuals with Lynch Syndrome

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Vancouver Prostate Centre Vancouver, Canada

Who Is Running the Clinical Trial?

Tampere University Hospital Lead Sponsor

Tampere University Collaborator

References

1. United States pubmed.ncbi.nlm.nih.gov

Evaluation of Urinalysis-Based Screening for Urothelial Carcinoma in Patients With Lynch Syndrome. [2021] Approximately 5% to 10% of patients with Lynch syndrome develop urothelial carcinoma. Current screening recommendations vary and are based on expert opinion. Practices need to be evaluated for clinical effectiveness. Our program utilizes urinalysis as a screening test, followed by additional evaluation of microscopic hematuria.

2. United States pubmed.ncbi.nlm.nih.gov

A possible noninvasive method for the detection of bladder cancer in patients: microsatellite analysis of free DNA in urine and blood. [2019] Six microsatellite markers were selected to detect shifts or loss of heterozygosity (LOH) in urine, serum, and plasma samples of 44 bladder cancer patients. After centrifugation at 15,000 g, we used supernatants for DNA analysis only. Tumor specimens were obtained by transurethral resection (TUR). Genetic alterations were detected in 33 of the 44 bladder tumors (75%). After polymerase chain reaction (PCR), DNA was detectable in 96% of all body fluid samples. Twenty-six percent of the detected microsatellite alterations of free DNA were tumor-specific, but 82% of all microsatellite changes of the tumors could be detected in body fluids. The study indicates that the simultaneous and multiple investigations of highly specific microsatellite markers could have a clinical relevance as a noninvasive tool for diagnosis and screening of bladder cancer. However, new ways for the sensitive DNA isolation of body fluids are needed.

3. England pubmed.ncbi.nlm.nih.gov

Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy. [2020] Current non-invasive approaches for detection of urothelial cancers are suboptimal. We developed a test to detect urothelial neoplasms using DNA recovered from cells shed into urine. UroSEEK incorporates massive parallel sequencing assays for mutations in 11 genes and copy number changes on 39 chromosome arms. In 570 patients at risk for bladder cancer (BC), UroSEEK was positive in 83% of those who developed BC. Combined with cytology, UroSEEK detected 95% of patients who developed BC. Of 56 patients with upper tract urothelial cancer, 75% tested positive by UroSEEK, including 79% of those with non-invasive tumors. UroSEEK detected genetic abnormalities in 68% of urines obtained from BC patients under surveillance who demonstrated clinical evidence of recurrence. The advantages of UroSEEK over cytology were evident in low-grade BCs; UroSEEK detected 67% of cases whereas cytology detected none. These results establish the foundation for a new non-invasive approach for detection of urothelial cancer.

4. England pubmed.ncbi.nlm.nih.gov

Prevalence of Lynch syndrome among patients with upper urinary tract carcinoma in a Japanese hospital-based population. [2020] The prevalence of Lynch syndrome and the use of universal tumor screening to identify Lynch syndrome among unselected patients with upper urinary tract urothelial carcinoma, which is associated with Lynch syndrome, have not been closely investigated yet.

5. United States pubmed.ncbi.nlm.nih.gov

Universal Point of Care Testing for Lynch Syndrome in Patients with Upper Tract Urothelial Carcinoma. [2022] Patients with Lynch syndrome are at risk for upper tract urothelial carcinoma. We sought to identify the incidence and most reliable means of point of care screening for Lynch syndrome in patients with upper tract urothelial carcinoma.

6. United States pubmed.ncbi.nlm.nih.gov

Mutational Analysis in Urinary Cell-Free DNA: KRAS in Colorectal Cancer. [2021] Urinary cell-free DNA offers an important noninvasive source of material for genomic testing also for nonurological tumors. Its clinical utility in monitoring tumor evolution and treatment failure is promising. Here we describe a method to detect cancer mutations into urine from patients affected by colorectal cancer.

7. United States pubmed.ncbi.nlm.nih.gov

Upper Tract Urothelial Carcinoma in the Genetically Predisposed Patient: Role of Urinary Markers in Predicting Recurrence. [2020] Background: Upper tract urothelial carcinoma (UTUC) is an uncommon disease that is diagnosed clinically by the selective use of urine cytology, urine biomarkers, and imaging of the upper tract. We present a case of a patient with Lynch syndrome and high-grade UTUC that was diagnosed by an abnormal Cxbladder assay, prompting further endoscopic examination. Case Presentation: A 59-year-old Caucasian female with a history of endometrial cancer and bladder cancer with Lynch syndrome presented for evaluation of recurrent urothelial carcinoma. Her previous bladder tumors have been T1 high grade and Ta high grade and have been treated with resection and multiple cycles of intravesical Bacillus Calmette-Guerin (BCG) therapy. She had also undergone a robotic left distal ureterectomy and psoas hitch for a high-grade distal ureteral tumor. Surveillance cystoscopy 7 months after revealed a biopsy-confirmed bladder tumor, which was resected, and she was started on maintenance BCG therapy. At presentation, follow-up urine cytology and UroVysion studies were negative. Cxbladder test was also initially negative. However, during close clinical monitoring, the Cxbladder test became positive. Cystoscopy was once more performed, which was unremarkable. Bilateral ureteroscopy was performed, revealing high-grade upper tract renal papillary carcinoma (UTUC) in the left renal pelvis. The patient declined a nephroureterectomy. She was treated with two sessions of holmium laser ablation of the left renal pelvis tumor and underwent 6 weekly courses of BCG + interferon instilled into her left renal pelvis using a 5F open-ended catheter. Repeat urine cytology, UroVysion, and Cxbladder tests were negative after completion of upper tract BCG therapy. Conclusion: Cxbladder test may be useful and an adjunct to urine cytology and the UroVysion FISH assay to evaluate patients at high risk for recurrent UTUC.