Phase II Study of Intravenous and Intraperitoneal Paclitaxel and Oral Nilotinib for Peritoneal Carcinomatosis From Ovarian, Colorectal, or Appendiceal Cancer

• Status: Not yet recruiting
• Trial end date: 2031-12-30
• Target enrollment: 0
• Participant gender: All

Summary

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 ovarian, colorectal, or appendiceal 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 non-mucinous peritoneal carcinomatosis of ovarian, colorectal, or appendiceal 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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Paclitaxel

Criteria

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria.

• Histological confirmation of non-mucinous peritoneal carcinomatosis from ovarian, colorectal, or appendiceal 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 PCI score > 30 on screening laparoscopy or with extensive small bowel serosal involvement

• Age >= 18 years

• ECOG performance status <= 2 (Karnofsky >= 60%).

• Participants must have adequate organ and marrow function as defined below:

• Leukocytes >= 3,000/mcL

• Absolute neutrophil count >= 1,000/mcL

• Platelets >= 100,000/mcL

• Total bilirubin within <= 1.5x institutional upper limit of normal (ULN)

• AST (SGOT)/ ALT (SGPT) <= 2.5x institutional ULN

• Serum amylase and lipase <= 1.5x institutional ULN

• Serum potassium and magnesium greater than institutional lower limit of normal

• Creatinine <= 1.5 mg/dL or creatinine clearance >= 60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal calculated using eGFR

• Breastfeeding participant must agree to discontinue breastfeeding.

• Females of child-bearing potential 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 a female suspect she is pregnant while she is participating in this study, she should inform her 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

• Participants must agree to co-enrollment on protocol 06-C-0213, Tissue Procurement Protocol

EXCLUSION CRITERIA:

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 has received an investigational agent within 30 days prior to the start of study treatment.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs.

• Participants who have received intravenous chemotherapy within the last 4 weeks or who have undergone major surgery within the last 12 weeks prior to the start of study treatment.

• Previous intraperitoneal chemotherapy within the last 6 months.

• 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 women are excluded from this study.

• Patients with HIV who have detectable viral load, or whose ART contains QTc Prolonging Medications or CYP3A4 Inhibitors regardless of viral load. (NOTE: Patients 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 paracentesis procedures in the 30 days prior to initial laparoscopy.

• Advanced hepatic failure, as indicated by Child-Pugh Class C cirrhosis.

• Sensory/motor neuropathy >= Grade 2