Identification and Treatment Of Micrometastatic Disease in Stage III Colon Cancer

Stage III Colon Cancer Clinical Trial

Official title: Early Identification and Treatment of Occult Metastatic Disease in Stage III Colon Cancer

Status Recruiting

Clinical Trial Summary

This research study is comparing two standard of care treatment options based on blood test results for participants who have metastatic colon cancer.

The names of the potential treatments involved in this study are:

• Active surveillance

• FOLFIRI treatment

• Nivolumab treatment

• Encorafenib/Binimetinib/Cetuximab treatment

• Trastuzumab + Pertuzumab

Clinical Trial Description

The FDA (the U.S. Food and Drug Administration) has approved FOLFIRI, comprised of Irinotecan, Leucovorin, and 5-Fluorouracil, as a treatment option for metastatic colon cancer in the Stage IV setting.

• After diagnosis and surgical removal of tumors, individuals with metastatic colon cancer commonly receive what is called adjuvant chemotherapy treatment, commonly utilizing treatment plans called FOLFOX, CAPOX, or therapy with 5-Fluorouracil.

• If all the cancer is not killed, the investigators may be able to detect tumor in the blood called circulating tumor DNA (ctDNA). This is genetic material unique to metastatic colon cancer that may be present in the blood stream, and it can be identified through a ctDNA blood test. If ctDNA is present in the blood stream, it is commonly called micro-metastatic disease (meaning disease that can't be seen detected by CT scans but may be there in the blood). Cancer researchers believe that ctDNA in the blood stream may be an indicator that cancer is more likely to recur.

• After initial adjuvant chemotherapy, it is standard for individuals to begin active surveillance, where they do not receive further treatment but instead undergo frequent tumor imaging scans to see if their cancer is stable, growing, or coming back. The investigators plan to see if additional therapy, where FOLFIRI (comprised of Irinotecan, Leucovorin, and 5-Fluorouracil) is administered can decrease recurrence. Typically, FOLFIRI is given when the disease is visibly recurrent.

• In addition, the investigators plan to include study groups of adjuvant nivolumab treatment and adjuvant Encorafenib/Binimetinib/Cetuximab treatment to see if these treatments can decrease recurrence. The FDA has not approved either of these as a treatment options for metastatic colon cancer in the Stage IV setting.

• Patients who have a greater than normal number of genetic markers called microsatellites are called MSI-H. Because tumor cells with these features tend to have more genetic mutations than tumor cells without them, they are more likely to be recognized by the immune system. Nivolumab is an anti-PD-1 antibody. It works by attaching to and blocking a molecule called PD-1. PD-1 is a protein that is present on different types of cells in your immune system and controls parts of your immune system by shutting it down. Antibodies that block PD-1 can potentially prevent PD-1 from shutting down the immune system, thus potentially allowing immune cells to recognize and destroy cancer cells.

• Encorafenib in combination with binimetinib and cetuximab is one of the first effective regimens to target the BRAF V600E-mutation in colon cancer. When this mutation is present, it switches on pathway called the MAPK pathway which stimulates cell division and leads to uncontrolled cell growth. Encorafenib, binimetinib and cetuximab target different parts of this important signaling pathway in tumor cells with this mutation and slows down their growth and communication

However, in this research study, the investigators are

• determining whether there are differences in cancer recurrence in ctDNA positive participants treated with additional therapy versus put on active surveillance.

• determining whether there are differences in health in ctDNA positive participants treated with additional therapy versus put on active surveillance.

• examining whether patients who undergo further therapy experience changes in the ctDNA levels. ;

Related Conditions & MeSH terms

• Colonic Neoplasms
• Metastatic Colon Cancer
• Stage III Colon Cancer

• NCT number: NCT03803553
• Study type: Interventional
• Source: Massachusetts General Hospital
• Contact: Aparna Parikh, MD
• Phone: 617-724-4000
• Email: Aparna.Parikh@MGH.HARVARD.EDU
• Status: Recruiting
• Phase: Phase 3
• Start date: April 16, 2020
• Completion date: December 2027