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
- Conditions
- Gynecologic CancerGynecologic NeoplasmsPeritoneal CarcinomatosisPeritoneal NeoplasmsOvarian CancerOvarian NeoplasmsColorectal CancerColorectal NeoplasmsAppendiceal CancerAppendiceal Neoplasms
- Interventions
- Registration Number
- NCT05185947
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief 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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 19
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1/ IP Catheter Placement and Bidirectional Chemotherapy Nilotinib IP and IV paclitaxel administration with oral nilotinib 1/ IP Catheter Placement and Bidirectional Chemotherapy Paclitaxel IP and IV paclitaxel administration with oral nilotinib
- Primary Outcome Measures
Name Time Method 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 Inde... baseline, every 9 weeks during treatment, and then every 3 months for 3 years Rate of downstaging- i.e., the fraction of participants who are successfully downstaged to resectable based on PCI and PI discretion. The fraction of participants who are successfully down-staged to resectable by use of chemotherapy will be reported along with a 95% confidence interval.
- Secondary Outcome Measures
Name Time Method Evaluate participants quality of life (QOL) baseline, every 9 weeks while on treatment, then every 3 months for 3 years after completion of study therapy Outcomes from QOL will be reported using descriptive statistics, as well as comparing the results from before to after treatment: physical and mental health-related quality of life.
Assess clinicopathologic response to therapy baseline, every 9 weeks during treatment, and then every 3 months for 3 years Response rate by RECIST 1.1 and/or by PCI: the fractions with a clinical response will be reported for all participants along with a 95% confidence interval.
Evaluate the peritoneal progression-free survival (pPFS) probability and the percentage of participants who become resectable by individual histologies baseline, at peritoneal disease relapse from CR or peritoneal disease progression, for up to 3 years after completion of therapy Peritoneal progression-free survival (pPFS) probability and the percentage of participants who become resectable will be evaluated by individual histologies; median peritoneal progression-free survival (pPFS) will be reported using the Kaplan-Meier method, along with a 95% confidence interval for each histology. The fraction who are able to be down-staged to resectable will be reported for each histology along with a 95% confidence interval.
Measure overall survival (OS) and overall progression-free survival (PFS) baseline, at peritoneal disease relapse from CR or peritoneal disease progression, or death, for up to 3 years after completion of therapy Kaplan-Meier method will be used; a 95% confidence interval will be reported on the median overall survival (OS) and overall progression-free survival (PFS).
Evaluate safety and tolerability of therapy on-going throughout treatment Safety will be assessed by analyzing the type, grade and frequency of toxicities in addition to laboratory data and vital signs. Adverse events (AEs) will be assessed using CTCAE v.5.0
Determine peritoneal progression-free survival (pPFS) baseline, at peritoneal disease relapse from CR or peritoneal disease progression, for up to 3 years after completion of therapy Kaplan-Meier method will be used to evaluate peritoneal progression-free survival (pPFS); the median peritoneal progression-free survival (pPFS) will be reported along with a 95% two-sided confidence interval, to be done for all participants.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States