For this month’s Clinical Trials Conversations, we’re diving into colorectal cancer screening trials that evaluate noninvasive modalities, including two recently completed trials whose results were published in March, and two actively recruiting trials.

Trials evaluating the effectiveness of colorectal cancer screening tests most commonly report two key measures: the specificity and sensitivity of the test. Specificity describes how well the test can correctly identify healthy individuals. Tests with high specificity have a low false positive rate as they can more accurately rule out people who are healthy, ensuring few to no individuals are wrongly told they might have colorectal cancer when they don’t. Sensitivity describes how well the tests can identify individuals with colorectal cancer or advanced precancerous polyps.

Recently completed trials

Evaluation of the ctDNA LUNAR Test in an Average Patient Screening Episode (ECLIPSE) (ctDNA LUNAR-2 test, Guardant Health)

NCT04136002

Manju: This past March, the results of the ECLIPSE 试验 被发表在 新英格兰医学杂志 (NEJM). This trial looked at the performance of a cell-free DNA (cfDNA) blood-based test in detecting colorectal cancer or advanced precancerous polyps in an average-risk population eligible for screening. It is a prospective, observational multi-site study without randomization.

Outcomes reported for this trial were the sensitivity and specificity of the test for colorectal cancer and for advanced precancerous polyps compared to screening colonoscopy.

The clinical validation cohort included 10,258 participants ages 45 and older, of which 7,861 met the eligibility criteria, had completed and valid colonoscopy results, had valid cfDNA blood-based test results, and were evaluable for final analysis.

A total of 83.1% (54 of 65) of the participants with colorectal cancer detected by colonoscopy had a positive cfDNA test and 16.9% (11 of 65) had a negative test, showing test sensitivity (ability to correctly detect those with cancer) of 83.1% for detection of colorectal cancer. Sensitivity for stage I, II, or III colorectal cancer was 87.5%, and sensitivity for advanced precancerous lesions was 13.2%.

A total of 89.6% of the participants without any advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions) identified on colonoscopy had a negative cfDNA blood-based test, whereas 10.4% had a positive cfDNA blood-based test, which indicates a specificity (ability to correctly identify a person without cancer) for any advanced neoplasia of 89.6%. Specificity for negative colonoscopy (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9%. The false positive rate for this test was 10.1, which means 10.1% of patients without cancer on colonoscopy had a positive blood test.

Based on their findings, in an average-risk screening population, this blood-based test had 83% sensitivity for colorectal cancer, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions.

Clinical Validation of An Optimized Multi-Target Stool DNA (Mt-sDNA 2.0) Test, for Colorectal Cancer Screening "BLUE-C" (mt-sDNA 2.0, Exact Sciences)

NCT04144738

马亚。 Results from the “BLUE-C” trial were published in the same issue of NEJM. The primary objective of this 20,000+ participant prospective trial was to assess the sensitivity and specificity of a “next generation” multi-target stool DNA test (mt-sDNA 2.0) compared to fecal immunochemical test (FIT) for detecting colorectal cancer in average risk adults ages 40 years and older.

Participants in this trial completed the mt-sDNA 2.0 test and the FIT followed by a screening colonoscopy. The mt-sDNA 2.0 screening test and FIT test results were not shared with the treating clinicians.

Of 20,176 participants, 54% (n=10,961) had a negative colonoscopy with non-cancerous findings, while 98 had colorectal cancer; 2,144 had advanced precancerous lesions; and 6,973 had nonadvanced adenomas.

The mt-sDNA 2.0 test showed 93.9% sensitivity for colorectal cancer. The test specificity for advanced neoplasia was 90.6%. Sensitivity for advanced precancerous lesions was 43.4% and specificity for non-neoplastic findings or negative colonoscopy was 92.7%.

With the FIT, sensitivity was 67.3% for colorectal cancer and 23.3% for advanced precancerous lesions; specificity was 94.8% for advanced neoplasia and 95.7% for non-neoplastic findings or negative colonoscopy.

Based on these results, the authors concluded that compared to FIT, mt-sDNA 2.0 test had better sensitivity for CRC (93.9% versus 67.3%) and for advanced precancerous lesions (43.4% versus 23.3%) but had lower specificity for advanced neoplasia (90.6% versus 94.8%).

Actively recruiting trials

Collecting Blood Samples from Patients with and without Cancer to Evaluate Tests for Early Cancer Detection

NCT05334069

Manju: This NCI Alliance for Clinical Trials in Oncology is recruiting 2,000 participants across 659-sites for a case-control prospective observational study. This trial will collect blood and tissue samples from participants with a cancer diagnosis and participants without a cancer diagnosis (both with and without suspicion of cancer) to evaluate tests for early cancer detection. Collecting and storing samples of blood and tissue from patients with and without cancer to study in the laboratory may help researchers develop tests for the early detection of cancers.

The primary outcome is to have blinded reference set of cancer versus non-cancer blood samples and the secondary outcomes include test performance at the time of initial cancer diagnosis by tumor type and test performance at the time of initial cancer diagnosis by clinical stage.

Participants will complete a questionnaire at the baseline. They will undergo collection of blood samples at registration and at 12 months after registration. Patients with a cancer diagnosis may undergo collection of tissue samples at registration and 12 months after registration.

After completion of study, participants are followed up at one year.

A Prospective, Multi-center, Observational Study for Signal-C Test Evaluation (cfDNA Signal-C®, Universal DX)

NCT06059963

Maia: This trial is for individuals ages 45 to 84 years with an average risk of developing colorectal cancer and are scheduled to undergo a standard-of-care screening colonoscopy and willing to consent to a blood sample.

The blood sample will be assessed with Signal-C^®, a plasma circulating free-DNA test, to detect colorectal cancer and advanced precancerous lesions.

The clinical trial aims to confirm if Signal-C^® accurately detects colorectal cancer with sensitivity of 93% and specificity of 92%, and pre-cancerous lesions (advanced adenomas), with 54% sensitivity and 92% specificity.

Get Screened for Colorectal Cancer

Early detection could prevent the majority of CRC–related deaths but, unfortunately, over one-third of the eligible population is not up to date with screening. Alternative, less invasive or noninvasive tests, as those described here, have the potential to improve adherence. Ultimately, these tests will identify people who need to undergo colonoscopy to confirm the diagnosis and help save lives.

It’s important to note: Only colonoscopies allow for the detection and removal of precancerous polyps, as well as identifying cancer early, when it is in the most treatable stages.

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