CCGA Substudy Demonstrates Project’s Potential to Map Cancer Genetics

Cleveland Clinic researchers are helping build a database that could lead to the development of a blood test for early-stage cancer and promises to shed new light on the biology of cancer at its initial stages. Results of a preplanned substudy of this multicenter clinical trial — the Circulating Cell-Free Genome Atlas (CCGA) — were recently presented at the American Society of Clinical Oncology (ASCO) meeting.

NCT02889978 at a glance

The observational study, funded by GRAIL Inc., has so far enrolled > 11,000 of 15,000 planned participants (70 percent with cancer, 30 percent noncancer) in order to characterize the population variation in cancer and non-cancer subjects. The research team will use deep sequencing of cell-free nucleic acids in the blood, an emerging biomarker for earlier cancer detection, to develop a detailed atlas of cancer genetics.

The Center for Clinical Genomics team, along with primary investigators Eric A. Klein, MD, Chair of Cleveland Clinic’s Glickman Urological & Kidney Institute, and Mikkael Sekeres, MD, MS, Director of Cleveland Clinic Cancer Center’s Leukemia Program, will help recruit more than 1,000 Cleveland Clinic patients over the age of 20.

“The complex nature of cancer makes it difficult to identify biomarkers for detection of early-stage cancer before symptoms appear,” says Dr. Sekeres. “The CCGA study will expand our knowledge about genomic profiles in cancer patients.”

Substudy methods and results

As presented at ASCO, the preplanned substudy of 1,627 participants collected blood from 878 participants with newly diagnosed, untreated cancer (20 tumor types, all stages) and 749 participants with no cancer diagnosis (controls) for plasma cell-free DNA (cfDNA) extraction. The team performed three prototype sequencing assays: paired cfDNA and white blood cell (WBC) targeted sequencing (507 genes, 60,000x) for single nucleotide variants/indels, cfDNA whole genome bisulfite sequencing (30x) for methylation, and paired cfDNA and WBC whole-genome sequencing (30x) for copy number variation. WBC sequencing identified the contribution of clonal hematopoiesis.

Results from this first set of patients demonstrate that:

• Strong biological signals are present in unscreened cancers that are typically diagnosed at late stages.
• Signals correlate highly across assays. With specificity set at 98 percent, sensitivity ranged from 56-80 percent for a wide range of early stage (I-III) cancers, many of which currently lack good screening tests.

“These exciting results suggest that these assays are sensitive and specific ways of detecting a variety of cancers at an early stage,” says Dr. Klein. “The results demonstrate the power of current sequencing technology and add to the growing trend of personalized cancer medicine.”

For more information, contact the Center for Clinical Genomics CCGA study team at 216.445.2164 or CCGAStudy@ccf.org.