Using ctDNA Blood Test for Earlier Detection and Treatment of Recurrence or Spread after Treatment for Stage 3 Colon Cancer

About the Study

The usual care after a person with stage 3 colon cancer has had surgery and chemotherapy is to begin active surveillance. This is a time when no additional treatment is given, but instead patients have frequent imaging scans to see if their cancer has come back.

This study is looking at whether a blood test known as circulating tumor DNA (ctDNA) can find signs of remaining cancer or recurrence after treatment earlier than standard active surveillance. People in the study who have evidence of cancer in their ctDNA test may receive additional treatment based on their test results. All participants will receive close monitoring with imaging tests and blood tests. The goal of this study is to learn if using ctDNA and additional treatment improves outcomes in people after treatment for stage 3 colon cancer. Currently, testing with ctDNA and additional treatment based on ctDNA results is not part of standard of care. 

What the Study Involves

In order to participate, people in this study will receive a ctDNA test to see if there is any evidence of cancer. People will be assigned to different screening and treatment groups based on the results of their ctDNA test and their tumors. Participants will know which group they are in and what treatment they are receiving.

Based on the results of this pre-screening evaluation, participants will be placed into groups and will receive different treatments and follow up depending on which group they are in. Participants will be followed for 5 years.

For people whose pre-screening ctDNA test shows no evidence of cancer cells in the bloodstream (ctDNA negative):

• People assigned to this group will receive active surveillance. They will have imaging and blood tests to look at tumor markers and ctDNA every 3 months for a year. People who test ctDNA-positive during this time will be assigned to one of the study groups below based on their biomarker results. 

For people whose pre-screening ctDNA test shows evidence of cancer cells in the bloodstream (ctDNA positive):

People who are ctDNA positive will be assigned to one of the groups below based on the presence or absence of additional tumor biomarkers.

• People who are positive for the following biomarkers will be assigned to the following groups and will receive additional treatment as described.
  • MSI-H group: People who are ctDNA positive, and have a tumor biomarker called MSI-H will receive additional treatments with the immunotherapy drug, Tecentriq (atezolizumab) weekly. Tecentriq is given as an IV (intravenous) injection every 4 weeks. Participants will receive up to 12 treatments.  
  • BRAF mutation group: People who are ctDNA positive and have a tumor biomarker called a BRAF mutation will receive additional treatment with the oral targeted therapies, Braftovi (encorafenib) and Mektovi (binimetinib) every day for up to 24 weeks. 
  • HER2-positive group: People who are ctDNA positive and have a tumor biomarker called HER2-positive, will receive a combination of Herceptin (trastuzumab) and Perjeta (pertuzumab) by iv injection every 3 weeks for up to 24 weeks. 
• Participants who are ctDNA positive but test negative for the additional biomarkers listed above will be randomly placed into one of two groups:
  • Group 1 will receive additional cycles of FOLFIRI chemotherapy given by iv injection on days 1 and 3 of a 2-week cycle (every 2 weeks) for up to 24 weeks (12 cycles).
  • Group 2 will receive active surveillance. For the first 6 months of the study, they will have imaging every 3 months and will have blood draws to look at ctDNA every 1 month. After 6 months, they will have imaging and ctDNA every 3 months for a year. They may receive additional imaging and blood draws if requested by their doctor.

Study Locations

Boston, Massachusetts
Massachusetts General Hospital
Contact: Aparna Parikh, MD       aparna.parikh@mgh.harvard.edu   

Boston, Massachusetts
Dana Farber Cancer Institute
Contact: Marios Giannakis, MD       MGIANNAKIS@PARTNERS.ORG   

People who meet all of the following may be eligible:

• 18 years or older with stage 3 colon cancer that has been completely removed by surgery.
• have received standard chemotherapy after their colon cancer was surgically removed. 
• have a life expectancy greater than 3 months.
• have normal organ function.
• are not pregnant.
• are willing to use two forms of effective contraception.

The following people may not be eligible:

• are receiving an experimental treatment
• received neoadjuvant chemotherapy (chemotherapy before surgery)
• have metastatic cancer, cancer that has spread to other parts of the body.
• are unable to get standard chemotherapy or immunotherapy.
• have had more than 3-6 months of standard chemotherapy or immunotherapy.
• have had anticancer treatment within 30 days before the start of the study.
• have another uncontrolled illness such as an infection or heart condition.
• have psychiatric or substance use disorders. 
• have an additional cancer diagnosis that is progressing or requires treatment.