Gynecologic CancerPhase 2NCT05185947
Intravenous and Intraperitoneal Paclitaxel and Oral Nilotinib for Peritoneal Carcinomatosis
A Phase 2 study testing Paclitaxel, Nilotinib and ECG in people with Gynecologic Cancer and Gynecologic Neoplasms, run by National Cancer Institute (NCI) at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gynecologic Cancer, Gynecologic Neoplasms, Peritoneal Carcinomatosis
- What is being tested?
- Paclitaxel, Nilotinib and ECG
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Oct 2022to 27 Jan 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
- Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/Alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) <= 3x institutional ULN, or <= 5.0x ULN in participants with liver metastases (only)
- Serum potassium and magnesium greater than institutional lower limit of normal
- Creatinine <= 1.5 mg/dL or creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal calculated using estimated glomerular filtration rate (eGFR)
- Nursing (including breastfeeding) participant must agree to discontinue nursing.
- Individuals of child-bearing potential (IOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 90 days after last study treatment. Should an individual of child-bearing potential suspect to be pregnant while participating in this study, the individual should inform the treating physician immediately.
- Ability of participant to understand and the willingness to sign a written informed consent document.
- Participants must agree to co-enrollment on the tissue collection protocol 13C0176, Tumor, Normal Tissue and Specimens from Patients Undergoing Evaluation or Surgical Resection of Solid Tumors
Who cannot join
- 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.
- Note: Exclusion of participants who have undergone major abdominal surgery within the last 12 weeks prior to start of study treatment is to allow for scar tissue formation from that surgery to stabilize. Participant ECOG performance status will be checked to account for prolonged or difficult recoveries from other types of major surgery that would appropriately influence eligibility assessment.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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
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.
Read more
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.
Read the 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 National Institutes of Health (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
- Being tested
- Paclitaxel, Nilotinib, ECG, CT Scan CAP, Laparoscopy
- Keywords
- Taxol, Tasigna, Peritoneal Carcinomatosis Index (PCI), Cytoreductive Surgery (CRS), Unresectable, Percent necrosis, Ki-67, Peritoneal Metastasis, Progression Free Survival
- Medical subject headings
- Genital Neoplasms, Female, Peritoneal Neoplasms, Ovarian Neoplasms, Colorectal Neoplasms, Appendiceal Neoplasms, Cholangiocarcinoma, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaclitaxelDrug
Also called Taxol
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.
NilotinibDrug
Also called Tasigna
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.
ECGDiagnostic test
Also called Electrocardiogram
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).
CT Scan CAPDiagnostic test
Also called Computed Tomography Scan of the Chest, Abdomen, and Pelvis
Screening, Cycle 3 and 6 Day 1, Week 6, and every 3 months (± 2 weeks) for up to 3 years total.
LaparoscopyProcedure or surgery
Also called LAP
Screening, Day 0, Week -1, and Cycle 3 and 6, Week 3.
Peritoneal biopsies + ascites washingsProcedure or surgery
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).
| Study group | Role | What they receive |
|---|---|---|
| 1/ Intraperitoneal (IP) Catheter Placement and Bidirectional Chemotherapy | Experimental | Intraperitoneal (IP) and intravenous (IV) paclitaxel administration with oral nilotinib. Receives: Drug: Paclitaxel; Drug: Nilotinib; Diagnostic Test: ECG; Diagnostic Test: CT Scan CAP; Procedure: Laparoscopy; Procedure: Peritoneal biopsies + ascites washings |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: Baseline, every 9 weeks during treatment, and then every 3 months, up to 2 years
Secondary outcomes (10)
Overall Survival (OS)
OS is defined as the time from the start of treatment until time of death from any cause, for up to 3 years after completion of therapy. OS will be reported using the Kaplan-Meier method, along with a 95% confidence interval.
Measured: 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)
Percent pPFS will be reported using the Kaplan-Meier method, along with a 95% confidence interval for each histology. PFS is defined as the duration of time from the start of the treatment until time of peritoneal disease relapse from Complete Response (CR) or peritoneal disease progression, or death, whichever comes first, and after completion of therapy. Response was assessed by the Peritoneal Carcinomatosis Index (PCI) and the Response Evaluation Criteria in Solid Tumors (RECIST). Disease relapse is CR is PCI≤ 5 with negative histology of at least 3 peritoneal biopsies of suspect nodules and washings with negative cytology. Disease progression is at least 4 points increase in PCI. The appearance of one or more new lesions is also considered progressions. The Kaplan-Meier method calculates a survival function S(t), which represents the probability of "surviving" (remaining event-free) beyond time t. It is not calculated directly as a percentage.
Measured: 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
Safety will be assessed by analyzing the type, grade and frequency of toxicities. Adverse events (AEs) will be assessed using CTCAE v.5.0. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.
Measured: 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
Outcomes from QOL comparing results before to after treatment: Quality of life is assessed using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) questionnaire, a validated instrument that measures health-related quality of life. The FACT-C consists of the following subscales: Physical Well-Being (PWB): 7 items; score range 0-28, Social/Family Well-Being (SWB): 7 items; score range 0-28, Emotional Well-Being (EWB): 6 items; score range 0-24, Functional Well-Being (FWB): 7 items; score range 0-28, Colorectal Cancer Subscale (CCS):9 items; score range 0-36.The FACT-C total score is derived by summing all five subscale scores. Total score range: 0-144. For all subscales and the total score, higher values represent better quality of life and lower values represent worse quality of life. Questionnaires are administered at baseline, immediately prior to treatment Cycles 3 and 6, and at follow-up visits. A single value (average) was calculated for "during treatment immediate
Measured: 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)
Kaplan-Meier method will be used to evaluate peritoneal progression-free survival (pPFS). Median peritoneal progression-free survival (pPFS) was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and will be reported along with a 95% two-sided confidence interval. Progressive Disease is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on available studies. The appearance of one or more new lesions is also considered progression.
Measured: Baseline, at peritoneal disease relapse from Complete Response (CR) or peritoneal disease progression, and after completion of therapy, a median of 5.04 months
Percentage of Participants With a Clinicopathologic Response to Therapy by Response Evaluation Criteria in Solid Tumor (RECIST)v 1.1 Reported With a 95% Confidence Interval
The percentage of participants with a clinicopathologic response will be reported for all participants along with a 95% confidence interval. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on available studies. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.
Measured: Participants were followed from baseline, every 9 weeks during treatment, and then every 3 months through study completion for 27 months, 14 days
Median Overall Survival (OS)
Kaplan-Meier method will be used to evaluate median overall OS and will be reported with a 95% confidence interval. Overall survival (OS) is defined as the time from the start of the treatment until time of death from any cause, for up to 3 years after completion of therapy, assessed every 3 months (±2 weeks).
Measured: From time of initiation of study treatment to death or last follow-up, a median of 5.60 months
Percentage of Participants Who Become Resectable by Individual Histologies
The percentage of participants who become resectable will be evaluated by individual histologies.
Measured: Baseline, at peritoneal disease relapse from complete response (CR) or peritoneal disease progression, and after completion of therapy, up to 2 years
Participants Quality of Life (QOL) Using the EuroQoL 5-Dimension 5-Level (EQ-5D-5L) Questionnaire
Outcomes from QOL using the EuroQoL 5-Dimension 5-Level (EQ-5D-5L) questionnaire comparing results before to after treatment: physical and mental health-related quality of life will be reported. The EQ-5D-5L questionnaire assesses participants' physical and mental health-related quality of life (QOL). Questionnaires will be provided to the participants in an electronic application-based format to be filled out at baseline, and immediately prior to Cycles 3 and 6 and in follow-up. An index score of 100 is considered perfect health with no problems in any dimension. A score of 0.0 would be dead. A single value (average) was calculated for "during treatment immediately prior to Cycles 3 and Cycle 6".
Measured: Participants were followed from baseline (within 6 weeks prior to the start of treatment), during treatment immediately prior to Cycles 3 and 6, and after treatment (Follow-up at 4-8 weeks post-treatment) through study completion for 27 months, 14 days
Clinicopathologic Response to Therapy by Peritoneal Carcinomatosis Index (PCI) Reported for All Participants Along With a 95% Confidence Interval
Clinicopathologic response by PCI is reported with a 95% confidence interval. Complete Response (CR) 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) is at least 4 points increase in PCI. The appearance of one or more new lesions is also considered progression. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the PCI.
Measured: Baseline, every 9 weeks during treatment, and then every 3 months for 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2022
- Study start13 Oct 2022
- Primary completion27 Jan 2025
- Study completion27 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Gynecologic CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Andrew Blakely, National Cancer Institute (NCI)
- Investigators
- Andrew M Blakely, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05185947
- Sponsor's protocol ID
- 10000237
- Other IDs
- 000237-C
- Status last verified
- Jun 2026
- First submitted
- 8 Jan 2022
- Last updated
- 25 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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).
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05185947
- Acronym / sponsor ID
- 10000237
- Conditions
- Gynecologic Cancer, Gynecologic Neoplasms, Peritoneal Carcinomatosis, Peritoneal Neoplasms, Ovarian Cancer, Ovarian Neoplasms
- Keywords
- Taxol, Tasigna, Peritoneal Carcinomatosis Index (PCI), Cytoreductive Surgery (CRS), Unresectable, Percent necrosis, Ki-67, Peritoneal Metastasis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 13 Oct 2022 (actual)
- Primary completion
- 27 Jan 2025 (actual)
- Study completion
- 27 Jan 2025 (actual)
- First posted
- 11 Jan 2022 (actual)
- Results
- Posted 29 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 National Institutes of Health (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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1/ Intraperitoneal (IP) Catheter Placement and Bidirectional Chemotherapy | Experimental | Drug: Paclitaxel, Drug: Nilotinib, Diagnostic Test: ECG, Diagnostic Test: CT Scan CAP, Procedure: Laparoscopy, Procedure: Peritoneal biopsies + ascites washingsIntraperitoneal (IP) and intravenous (IV) paclitaxel administration with oral nilotinib. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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:
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PaclitaxelAlso: TaxolPaclitaxel: 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. | Drug | 1/ Intraperitoneal (IP) Catheter Placement and Bidirectional Chemotherapy |
| NilotinibAlso: TasignaOral 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. | Drug | 1/ Intraperitoneal (IP) Catheter Placement and Bidirectional Chemotherapy |
| ECGAlso: ElectrocardiogramScreening, 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). | Diagnostic test | 1/ Intraperitoneal (IP) Catheter Placement and Bidirectional Chemotherapy |
| CT Scan CAPAlso: Computed Tomography Scan of the Chest, Abdomen, and PelvisScreening, Cycle 3 and 6 Day 1, Week 6, and every 3 months (± 2 weeks) for up to 3 years total. | Diagnostic test | 1/ Intraperitoneal (IP) Catheter Placement and Bidirectional Chemotherapy |
| LaparoscopyAlso: LAPScreening, Day 0, Week -1, and Cycle 3 and 6, Week 3. | Procedure or surgery | 1/ Intraperitoneal (IP) Catheter Placement and Bidirectional Chemotherapy |
| Peritoneal biopsies + ascites washingsScreening (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). | Procedure or surgery | 1/ Intraperitoneal (IP) Catheter Placement and Bidirectional Chemotherapy |
Primary outcome
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
Time frame: 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
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.
Proportion of Participants Who Are Successfully Down-staged to Resectable by Use of Chemotherapy Reported Along With a 95% Confidence Interval.
Time frame: Baseline, every 9 weeks during treatment, and then every 3 months, up to 2 years
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).
10 secondary outcomes
Overall Survival (OS)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: Baseline, at peritoneal disease relapse from Complete Response (CR) or peritoneal disease progression, and after completion of therapy, a median of 5.04 months
Percentage of Participants With a Clinicopathologic Response to Therapy by Response Evaluation Criteria in Solid Tumor (RECIST)v 1.1 Reported With a 95% Confidence Interval
Time frame: Participants were followed from baseline, every 9 weeks during treatment, and then every 3 months through study completion for 27 months, 14 days
Median Overall Survival (OS)
Time frame: From time of initiation of study treatment to death or last follow-up, a median of 5.60 months
Percentage of Participants Who Become Resectable by Individual Histologies
Time frame: Baseline, at peritoneal disease relapse from complete response (CR) or peritoneal disease progression, and after completion of therapy, up to 2 years
Participants Quality of Life (QOL) Using the EuroQoL 5-Dimension 5-Level (EQ-5D-5L) Questionnaire
Time frame: Participants were followed from baseline (within 6 weeks prior to the start of treatment), during treatment immediately prior to Cycles 3 and 6, and after treatment (Follow-up at 4-8 weeks post-treatment) through study completion for 27 months, 14 days
Clinicopathologic Response to Therapy by Peritoneal Carcinomatosis Index (PCI) Reported for All Participants Along With a 95% Confidence Interval
Time frame: Baseline, every 9 weeks during treatment, and then every 3 months for 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew M Blakely, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Paclitaxel, Nilotinib and ECG in people with Gynecologic Cancer and Gynecologic Neoplasms, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2026.