A phase II Randomized controlled trial comparing short-course radiation and chemotherapy with or without intraperitoneal paclitaxel for locally advanced, non-metastatic signet-ring cell rectal cancers.

Colorectal cancer is a significant global health problem, ranking as the third most common cancer worldwide and the second leading cause of cancer-related deaths. In India, there is a concerning prevalence of a specific type of colorectal cancer called signet-ring cell adenocarcinoma, which makes up about 15% of rectal cancer cases. This is in stark contrast to the rest of the world where it’s less than 5%. Signet-ring cell cancers (SRCC) are particularly aggressive and don’t respond well to standard treatments, leading to poor survival rates.

Recent progress has been made in treating locally advanced rectal cancers (LARC). A new approach called total neoadjuvant therapy has improved disease-free survival by 7%. However, these advances don’t apply to SRCC cases because this type of cancer is unique in its behavior and aggressiveness. Most treatment failures in these cases were due to the cancer spreading to the peritoneum, which is the thin layer of tissue that lines the abdomen. This is a problem specific to signet-ring cell cancers.

To tackle this challenge, our upcoming study will compare the current standard of care, which involves short-course radiation and intravenous (IV) chemotherapy, with a new approach. This new approach includes short-course radiation, IV chemotherapy, and intraperitoneal (IP) chemotherapy for locally advanced, non-metastatic signet-ring cell rectal cancers. Our primary goal is to reduce treatment failures and improve disease-free survival, with a special focus on addressing the high rates of peritoneal failures often seen in SRCC.

The IP chemotherapy will deliver chemotherapy directly inside the abdomen by placing a device underneath the skin of the abdomen with tubes within the abdomen. Eligible patients that consent to the study will be randomly allocated to receive the standard of care treatment of radiation and chemotherapy versus standard of care along with IP chemotherapy.

We will be looking for reduction in disease related events at the end of one year and expect that the addition of IP chemotherapy will reduce treatment failures (disease progression, recurrence, or deaths) by an additional 20%.