NCT05185947

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

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: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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

Conditions

• Gynecologic Cancer
• Gynecologic Neoplasms
• Peritoneal Carcinomatosis
• Peritoneal Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Colorectal Cancer
• Colorectal Neoplasms
• Appendiceal Cancer
• Appendiceal Neoplasms

Interventions

Type	Name	Description
DRUG	Paclitaxel	Paclitaxel: Intraperitoneal (IP) paclitaxel will be dosed at 60 mg/m2 to be infused over 1 hour on Day 1 of each 3-week cycle; participants with unresectable, but stable or responding disease after C1 through C3 will dose increase IP paclitaxel to 80 mg/m2 for Cycles 4-6. Intravenous (IV) paclitaxel will be infused over 1 hour on Day 2 of the first week of Cycle 1, followed by Day 1 of the subsequent treatment weeks; IV paclitaxel will be dosed at 60 mg/m2 for Week 1 of Cycle 1 and, if tolerated, at 80 mg/m2 for subsequent treatments.
DRUG	Nilotinib	Oral nilotinib will be dosed at 300 mg twice daily. Nilotinib will be administered continually from the loading dose (Day -4) leading up to laparoscopy #2 onward.

Timeline

• Start date: 2022-10-13
• Primary completion: 2025-01-27
• Completion: 2025-04-04
• First posted: 2022-01-11
• Last updated: 2025-03-07

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study