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

NCT05185947 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10000237000237-C
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Taxol; Tasigna; Peritoneal Carcinomatosis Index (PCI); cytoreductive surgery (CRS); Unresectable; SMART System; necrosis; Ki-67; Peritoneal Metastasis; Progression Free Survival

Outcome Measures

Primary Outcomes (1)

• 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...

  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.

  baseline, every 9 weeks during treatment, and then every 3 months for 3 years

Secondary Outcomes (6)

• 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

• 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

• Evaluate safety and tolerability of therapy

  on-going throughout treatment

• 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

• 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

Study Arms (1)

1/ IP Catheter Placement and Bidirectional Chemotherapy

EXPERIMENTAL

IP and IV paclitaxel administration with oral nilotinib

Drug: Paclitaxel; Drug: Nilotinib

Interventions

Paclitaxel DRUG

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.

1/ IP Catheter Placement and Bidirectional Chemotherapy

Nilotinib DRUG

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.

1/ IP Catheter Placement and Bidirectional Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria.
• Histological confirmation of peritoneal carcinomatosis from colorectal, appendiceal, small bowel, gastric, cholangiocarcinoma, breast, ovarian, or other gynecologic (i.e., endometrial, fallopian tube, primary peritoneal, cervical) primary by the Laboratory of Pathology, NCI.
• Participants must have been treated with at least one line of approved systemic chemotherapy, with demonstrated resistance or lack of response
• Measurable or evaluable disease as defined by RECIST v1.1. criteria and/or by Peritoneal Carcinomatosis Index (PCI)
• Participants must be assessed to not be candidates for cytoreductive surgery, with laparoscopically assessed PCI score thresholds as indicated below:
• Primary Histology PCI Cutoff for Eligibility
• Gastric Total Score \>= 10 (out of 39 possible points)
• Others Total Score \>= 20 (out of 39 possible points)
• Any Jejunoileal Score \>= 4 (out of 12 possible points)
• Age \>= 18 years
• ECOG performance status \<= 2 (Karnofsky \>= 60%).
• Participants must have adequate organ and marrow function as defined below:
• Absolute neutrophil count \>= 1,000/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin within \<= 1.5x institutional upper limit of normal (ULN)

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study.
• Participants who are receiving any other investigational agents or who have received an investigational agent within 30 days prior to the start of study treatment.
• Participants with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs.
• Participants who have received systemic (i.e., oral or intravenous) chemotherapy or other anti-cancer therapy (i.e., immunotherapy) within either 5 half-lives or within 30 days of the last dose of individual agent(s) administered prior to the start of study treatment, whichever is shorter.
• Participants who have undergone major abdominal surgery within the last 12 weeks prior to the start of study treatment.
• Participants who have received previous intraperitoneal chemotherapy within the last 6 months prior to the start of study treatment
• Participants requiring the use of drugs known to prolong the QT interval or known to strongly inhibit CYP3A4, 2C8. Participants on such agents at the time of screening are permitted on study if an alternative that does not have the same pharmacokinetic interactions can be found.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Note: No subject will be excluded based on a social situation prior to consultation with the Department of Social Work.
• Pregnant individuals are excluded from this study.
• Participants with HIV who have detectable viral load, or whose ART contains QTc Prolonging Medications or CYP3A4 Inhibitors regardless of viral load. (NOTE: Participants with HIV who have an undetectable viral load and have been on stable doses of ART that does not prolong the QT interval or is a strong CYP3A4, 2C8 inhibitor are eligible).
• QTcF interval of \>= 450 msec at study entry, or congenital long QT syndrome.
• More than 3 liters of ascites present at initial laparoscopy, or history of more than two therapeutic paracentesis procedures, each yielding at least 1.5 liters of fluid, in the 30 days prior to initial laparoscopy, or confirmation of predominantly mucinous ascites at
• the time of screening laparoscopy.
• Advanced hepatic failure, as indicated by Child-Pugh Class C cirrhosis.
• Sensory/motor neuropathy \>= Grade 2

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Genital Neoplasms, Female; Peritoneal Neoplasms; Ovarian Neoplasms; Colorectal Neoplasms; Appendiceal Neoplasms; Necrosis

Interventions

Paclitaxel; nilotinib

Condition Hierarchy (Ancestors)

Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Abdominal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Cecal Neoplasms; Cecal Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Andrew M Blakely, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2022
• First Posted: January 11, 2022
• Study Start: October 13, 2022
• Primary Completion: January 27, 2025
• Study Completion: April 4, 2025
• Last Updated: March 7, 2025

Record last verified: 2025-03-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.@@@@@@Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)