Intestinal & Multivisceral Transplantation for Unresectable Mucinous Carcinoma Peritonei (TRANSCAPE)

Sponsor

Case Comprehensive Cancer Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06084780

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this prospective phase 2 study is to assess the efficacy and safety of intestinal or multivisceral transplantation for participants with PMP not amenable to other curative-intent treatments. Participants will undergo intestinal/multivisceral transplantation. Participants will be followed for 12 months to assess efficacy and safety.

Condition or Disease	Intervention/Treatment	Phase
Secondary Malignant Neoplasm of Retroperitoneum Secondary Malignant Neoplasm of Peritoneum Pseudomyxoma Peritonei	Procedure: Intestinal, Multivisceral or Modified Multivisceral Transplantation Drug: Alemtuzumab Drug: Tacrolimus Drug: Sirolimus	Phase 2

Detailed Description

Pseudomyxoma peritonei (PMP) is a rare clinical entity (approximately 2-4 cases per million people) characterized by extensive dissemination of mucinous ascites in the abdominal cavity. Relentless accumulation of mucin causes progressive abdominal distention, intestinal obstruction, malnutrition, cachexia, and ultimately death. As a rare disease, diagnosis is often late, and usually occurs when the disease is in a clinically advanced stage. The prognosis of PMP has been dramatically improved by the introduction of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). While outcomes are favorable for participants with disease amenable to CRS+HIPEC, the therapeutic options for participants with unresectable PMP are limited. Intestinal transplantation represents a therapeutic option in participants with unresectable PMP. Overall survival has been shown to improve with participants with unresectable PMP during an Oxford Transplant Center study. The goal of this study is to corroborate the Oxford results on an American cohort.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Prospective Case Series of Intestinal and Multivisceral Transplantation for Unresectable Mucinous Carcinoma Peritonei (TRANSCAPE)

Anticipated Study Start Date :

Apr 1, 2024

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intestinal, Multivisceral or Modified Multivisceral Transplantation Participants will undergo intestinal or modified multivisceral transplantation according to their disease extent. Participants will be followed for 12 months from the day of transplantation. Participants will undergo routine clinical follow-up according to standard protocols for the management of participants after visceral organ transplantation and standard oncological follow-up for participants with PMP.	Procedure: Intestinal, Multivisceral or Modified Multivisceral Transplantation Enrolled participants will enter the active transplant waiting list within one month of signing informed consent for study participation. Participants can be listed for: Isolated small bowel transplant (SBT): transplantation of the donor small intestine Modified multivisceral tran I lant (MMVT): transplantation of the donor pancreas and small intestine, with or without stomach Multivisceral transplant (MVT): transplantation of the donor pancreas, small intestine, and liver, with or without stomach Drug: Alemtuzumab A post-transplant, steroid-free immunosuppressive regimen will be utilized and will include Alemtuzumab as Antibody Induction Therapy. Participants will be administered two doses of Alemtuzumab (30 mg IV) on days 0 and 1. Drug: Tacrolimus A post-transplant, steroid-free immunosuppressive regimen will be utilized and will include Tacrolimus for maintenance. Participants will have Tacrolimus for the first 3 months. Dosing of Tacrolimus will depend on participant target level, starting with 0.05 mg/Kg bid. Drug: Sirolimus A post-transplant, steroid-free immunosuppressive regimen will be utilized and will include Sirolimus for maintenance. Participants will have Sirolimus after 3 months of Tacrolimus. Dosing of Sirolimus will depend on participant target level, starting with 2 mg od.

Arm

Intervention/Treatment

Experimental: Intestinal, Multivisceral or Modified Multivisceral Transplantation

Participants will undergo intestinal or modified multivisceral transplantation according to their disease extent. Participants will be followed for 12 months from the day of transplantation. Participants will undergo routine clinical follow-up according to standard protocols for the management of participants after visceral organ transplantation and standard oncological follow-up for participants with PMP.

Procedure: Intestinal, Multivisceral or Modified Multivisceral Transplantation

Enrolled participants will enter the active transplant waiting list within one month of signing informed consent for study participation. Participants can be listed for: Isolated small bowel transplant (SBT): transplantation of the donor small intestine Modified multivisceral tran I lant (MMVT): transplantation of the donor pancreas and small intestine, with or without stomach Multivisceral transplant (MVT): transplantation of the donor pancreas, small intestine, and liver, with or without stomach

Drug: Alemtuzumab

A post-transplant, steroid-free immunosuppressive regimen will be utilized and will include Alemtuzumab as Antibody Induction Therapy. Participants will be administered two doses of Alemtuzumab (30 mg IV) on days 0 and 1.

Drug: Tacrolimus

A post-transplant, steroid-free immunosuppressive regimen will be utilized and will include Tacrolimus for maintenance. Participants will have Tacrolimus for the first 3 months. Dosing of Tacrolimus will depend on participant target level, starting with 0.05 mg/Kg bid.

Drug: Sirolimus

A post-transplant, steroid-free immunosuppressive regimen will be utilized and will include Sirolimus for maintenance. Participants will have Sirolimus after 3 months of Tacrolimus. Dosing of Sirolimus will depend on participant target level, starting with 2 mg od.

Outcome Measures

Primary Outcome Measures

Overall Rate of Survival [12 months post operative]
To determine overall 12-month survival after intestinal or multivisceral transplantation in participants with unresectable PMP.

Secondary Outcome Measures

Overall Rate of Morbidity [90 days post operative]
Determine the morbidity of intestinal or multivisceral transplantation for participants with unresectable at 90 days by monitoring severe adverse events as classified according to Clavien-Dindo grade and comprehensive complication index.
Overall Rate of Morbidity [12 months post operative]
Determine the morbidity of intestinal or multivisceral transplantation for participants with unresectable at 12 months by monitoring severe adverse events as classified according to Clavien-Dindo grade and comprehensive complication index.
Overall Rate of Mortality [12 months post operative]
Determine cancer-related and transplant-related mortality after intestinal or multivisceral transplantation in participants with unresectable PMP.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects must have histologically confirmed pseudomyxoma peritonei (PMP)
Both low-grade mucinous carcinoma peritonei (LMCP) or high-grade mucinous carcinoma (HMCP), with or without signet ring cells as well as primary or recurrent disease, will be eligible.
PMP disease does not have any extra-abdominal metastases, with the exception of pulmonary involvement (nodal, parenchymal, and pleural).
PMP disease is extensive and not amenable to operative management, with or without liver, pancreas, stomach, or abdominal wall involvement.
Definition of Non-Resectable Disease-
Non-resectable PMP disease will be defined as the presence of at least one of the following conditions:
1. Extensive small bowel serosa involvement, where it is not possible to preserve at least 1.5-2 m of small bowel
1. Extensive infiltration of the pancreatic surface
1. Mesenteric involvement causing retraction
1. Need for complete gastric resection
1. Urete1ic obstruction
1. Liver disease with no chance to achieve R0 resection with liver remnant volume > 30%
1. Recurrent disease not amenable to further resection
Subjects do not have any other available curative treatment options.
Subjects can have previous abdominal operations, including CRS+HIPEC.
Age ≥ 18 and ≤ 75.
Pediatric participants were excluded as PMP is a disease that affects adults. Participants > 75 years of age are excluded as they are beyond the commonly accepted transplantability criteria.
Performance status ECOG ≤ 1.
Subjects must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Subjects with peritoneal carcinomatous originating from an etiology other than PMP.
Subjects receiving any other investigational agents.
Subjects with 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 either put participation at risk because of participation in the study, may influence the result of the study, or limit compliance with study requirements.
Pregnant women are excluded from this study because an intestinal transplant is a procedure that is not compatible with a viable pregnancy.
Subjects who are HIV-positive may be included in the study. HIV testing is required for the study as adequate HIV treatment is required prior to intestinal transplant due to the increased risk of infection following transplantation and treatment with immunosuppressive agents.