Intravenous and Intraperitoneal Paclitaxel and Oral Nilotinib for Peritoneal Carcinomatosis
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
2 other identifiers
interventional
21
1 country
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 intravenous (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 Computed tomography (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 intraperitoneal (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 National Institutes of Health (NIH) or with their local doctor.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Oct 2022
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 8, 2022
CompletedFirst Posted
Study publicly available on registry
January 11, 2022
CompletedStudy Start
First participant enrolled
October 13, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 27, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
January 27, 2025
CompletedResults Posted
Study results publicly available
May 29, 2026
CompletedJune 25, 2026
June 1, 2026
2.3 years
January 8, 2022
January 22, 2026
June 1, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Proportion of Participants Who Are Successfully Down Staged to Resectable Based on Peritoneal Carcinomatosis Index (PCI) and Principal Investigator (PI) Discretion Reported Along With a 95% Confidence Interval
We calculated the rate of downstaging of peritoneal disease burden to become resectable based on PCI score of initial and subsequent laparoscopy, or magnetic resonance imaging and/or computed tomography imaging if laparoscopy is not planned. Disease burden will be considered stable when PCI score at laparoscopy (lap) #3 is \< 4 points higher or lower compared to PCI score at lap #2. Complete Response is PCI≤ 5 with negative histology of at least 3 peritoneal biopsies of suspect nodules and washings with negative cytology. Partial Response (PR) is at least 4 points decrease in PCI. Progressive Disease (PD) has at least 4 points increase in PCI. Stable Disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the PCI. To document PCI scoring for each participant, the rubric will be completed following each laparoscopy. The PCI is scaled from 0-39, with higher scores indicating higher disease burden and worse prognosis.
Participants were followed from baseline (within 6 weeks prior to the start of treatment), and every 9 weeks during treatment through study completion for 27 months, 14 days
Proportion of Participants Who Are Successfully Down-staged to Resectable by Use of Chemotherapy Reported Along With a 95% Confidence Interval.
The proportion of participants who are successfully down-staged to resectable by use of chemotherapy will be reported along with a 95% confidence interval. This outcome measure evaluates how many participants with initially inoperable (unresectable) peritoneal carcinomatosis became eligible for surgery after receiving bidirectional chemotherapy (intravenous and intraperitoneal paclitaxel and oral nilotinib).
Baseline, every 9 weeks during treatment, and then every 3 months, up to 2 years
Secondary Outcomes (10)
Overall Survival (OS)
Participants were followed from time of initiation of study treatment to death or last follow-up through study completion for 27 months, 14 days
Percent Probability of Peritoneal Progression-free Survival (pPFS)
From baseline, at peritoneal disease relapse from Complete Response (CR) or peritoneal disease progression, and after completion of therapy up to a percent probability of PFS at 12 months
Number of Grades 3, 4, and/or 5 Serious and/or Non-serious Toxicities by Type Assessed Using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Day-4 through completion of surveillance post-treatment, up to 2 years.
Participants Quality of Life (QOL) Using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) Instrument
Participants were followed from baseline (within 6 weeks prior to start of treatment), and immediately prior to Cycle 3 (one cycle is 21 days) and Cycle 6 and in follow-up, up to 8 weeks post-treatment
Median Peritoneal Progression-free Survival (pPFS)
Baseline, at peritoneal disease relapse from Complete Response (CR) or peritoneal disease progression, and after completion of therapy, a median of 5.04 months
- +5 more secondary outcomes
Other Outcomes (1)
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Day-4 through completion of surveillance post-treatment, up to 2 years
Study Arms (1)
1/ Intraperitoneal (IP) Catheter Placement and Bidirectional Chemotherapy
EXPERIMENTALIntraperitoneal (IP) and intravenous (IV) paclitaxel administration with oral nilotinib.
Interventions
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.
Paclitaxel: Intraperitoneal (IP) paclitaxel will be dosed at 60 mg/m\^2 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.
Screening, Week -1, Cycle 1 and 4 Day 1 (±3 days at start of cycle), Cycle 2 and 5 Day 1 (±3 days at start of cycle), Cycle 3 and 6 Day 1 (±3 days at start of cycle) and 4-8 Weeks post-therapy (±2 weeks).
Screening, Cycle 3 and 6 Day 1, Week 6, and every 3 months (± 2 weeks) for up to 3 years total.
Screening, Day 0, Week -1, and Cycle 3 and 6, Week 3.
Screening (intra-op), Week -1, Day 0 (intra-op), and on treatment (± 1 day), Cycle 3 and 6, Week 3 (intra-op). Biopsy only done if deemed eligible per laparoscopy (only performed during laparoscopy).
Eligibility Criteria
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, national Cancer Institute (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 the Response Evaluation Criteria in Solid Tumors (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 Peritoneal Cancer Index (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
- Eastern Cooperative Oncology Group (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)
- +7 more criteria
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 cytochrome P450 3A4 (CYP3A4), cytochrome P450 CYP (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 human immunodeficiency virus (HIV) who have detectable viral load, or whose Antiretroviral therapy (ART) contains corrected QT interval (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).
- QT corrected for heart rate by Fridericia's cube root formula (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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Andrew Blakely
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Andrew M Blakely, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
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
January 27, 2025
Last Updated
June 25, 2026
Results First Posted
May 29, 2026
Record last verified: 2026-06
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 Genomic Data Sharing (GDS) plan for as long as database is active.
- Access Criteria
- Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).