Study of Intravenous and Intraperitoneal Paclitaxel and Oral Nilotinib for Peritoneal Carcinomatosis From Colorectal, Appendiceal, Small Bowel, Gastric, Cholangiocarcinoma, Breast, Ovarian, or Other Gynecologic Primary Cancer

Colorectal Cancer Clinical Trial

Official title: Phase II Study of Intravenous and Intraperitoneal Paclitaxel and Oral Nilotinib for Peritoneal Carcinomatosis From Colorectal, Appendiceal, Small Bowel, Gastric, Cholangiocarcinoma, Breast, Ovarian, or Other Gynecologic Primary Cancer

Status Recruiting

Clinical Trial Summary

Background:

Tumors that have spread to the lining of the abdomen from other cancers, such as cancer of the appendix, colon, or ovary, are called peritoneal carcinomatosis. In most cases, outcomes are poor. Researchers want to test a new treatment.

Objective:

To learn if the combination of oral nilotinib plus paclitaxel given by IV and directly into the abdomen can reduce tumors enough for people to have surgery.

Eligibility:

Adults aged 18 and older with peritoneal carcinomatosis that is too widespread for surgery.

Design:

Participants will be screened with:

Physical exam

Medical history

Blood and urine tests

Electrocardiogram

Laparoscopy. They will get general anesthesia. Small cuts will be made in their abdomen. Tissue and fluid samples will be taken.

Surveys about their health

CT scans of their torso

Participants will have up to 4 more laparoscopies. During the first procedure, a port will be placed under the skin of their abdomen (an IP port). It will be attached to a catheter that is placed in their abdomen.

Participants will get treatment in 3-week cycles, for 3 or 6 cycles. They will take nilotinib by mouth twice daily. They will get paclitaxel by IP port (once per cycle) and by IV (twice per cycle). After cycles 3 and 6, they will have a laparoscopy and CT scans. Then they may take nilotinib and get IV paclitaxel for up to 1 year.

At study visits, participants will repeat some screening tests.

About 6 weeks after treatment ends and then every 3 months for 3 years, participants will have follow-up visits at NIH or with their local doctor.

Clinical Trial Description

Background:

• Peritoneal carcinomatosis is uniformly fatal if untreated; despite advances in systemic chemotherapy, cytoreductive surgery, and intraperitoneal chemotherapy, survival remains poor for the majority of patients

• The combination of oral nilotinib and intravenous paclitaxel has demonstrated pre-clinical and clinical synergism in the treatment of solid tumors, with an ongoing Phase I trial at the NIH

• The synergy of oral nilotinib with intraperitoneal paclitaxel remains to be characterized

• This study involves the combination of intravenous and intraperitoneal paclitaxel and oral nilotinib for unresectable peritoneal carcinomatosis from colorectal, appendiceal, small bowel, gastric, cholangiocarcinoma, breast, ovarian, or other gynecologic primary histologies

Objective:

-To evaluate efficacy of bidirectional chemotherapy using intraperitoneal and intravenous paclitaxel and oral nilotinib by calculating the rate of downstaging of peritoneal disease burden to become resectable, based on Peritoneal Carcinomatosis Index (PCI)

Eligibility:

• Participants >= 18 years of age with histologically confirmed peritoneal carcinomatosis of colorectal, appendiceal, small bowel, gastric, cholangiocarcinoma, breast, ovarian, or other gynecologic primary histology

• Demonstrated resistance or lack of response to at least one line of already approved and available systemic chemotherapy

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs

• No intraperitoneal chemotherapy within the last six months

• Deemed unable to undergo complete cytoreduction

Design:

• Phase II open-label, non-randomized study

• After confirmation of eligibility, at the time of diagnostic laparoscopy, biopsies will be taken, and an intraperitoneal catheter will be placed for subsequent chemotherapy administration

• Up to 6 cycles will be planned, with restaging laparoscopy and biopsies after Cycles 3 and 6 ;

Related Conditions & MeSH terms

• Appendiceal Cancer
• Appendiceal Neoplasms
• Carcinoma
• Cholangiocarcinoma
• Colorectal Cancer
• Colorectal Neoplasms
• Genital Neoplasms, Female
• Gynecologic Cancer
• Gynecologic Neoplasms
• Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Peritoneal Carcinomatosis
• Peritoneal Neoplasms

• NCT number: NCT05185947
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Audra A Satterwhite, R.N.
• Phone: (240) 858-3552
• Email: audra.satterwhite@nih.gov
• Status: Recruiting
• Phase: Phase 2
• Start date: October 13, 2022
• Completion date: December 30, 2031