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.
Additional locations may be listed on ClinicalTrials.gov for NCT05185947.
See trial information on ClinicalTrials.gov for a list of participating sites.
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
Lead OrganizationNational Cancer Institute
Principal InvestigatorAndrew M Blakely