Immunotoxin in Peritoneal Carcinomatosis- ImmunoPeCa Trial

Study Overview
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Brief Summary
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The purpose of this study is through a phase I/II clinical trial to assess the safety and toxicity of intraperitoneally administered MOC31PE immunotoxin, given on the 1.postoperative day after cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for peritoneal metastases from colorectal cancer (CRC).

Detailed Description
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MOC31PE is an immunotoxin that has previously been evaluated in a phase I clinical study involving patients with advanced EpCAM positive carcinoma to assess the safety and tolerability profile and the pharmacokinetic behavior of the compound. In this study, the compound was administered intravenously and was well tolerated. MOC31PE will now be evaluated on the same parameters in a new phase I/II clinical trial, where the drug will be administered intraperitoneally to patients with peritoneal metastases from EpCAM positive colorectal carcinomas.

Official Title
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Phase I/II Trial of MOC31PE Immunotoxin in Peritoneal Carcinomatosis From Colorectal Carcinoma

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Drug: MOC31PE Immunotoxin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Histologically verified EpCAM positive colorectal cancer Ambulatory with Eastern Cooperative Oncology Group (ECOG) performance status 0-1 at the time of surgery At least 18 years of age Suspected isolated peritoneal carcinomatosis upon radiologic work-up Complete cytoreduction at surgery and mitomycin C given as standard HIPEC procedure Peritoneal Cancer Index (PCI) ≤ 20 Laboratory values at inclusion: Absolute neutrophil count (ANC) > 1.5 x 10^9/L Platelets > 100 x 10^9/L Hb > 9g/dL Creatinine ≤ 2x upper limit of normal Bilirubin < 2.0x the upper limit of normal Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2. 5x the upper limit of normal Albumin levels > 30 g/L International normalised ratio (INR) <1.3 Signed informed consent and expected cooperation with respect to treatment and follow-up must be obtained and documented according to International Conference of Harmonisation- Good clinical Practice (ICH GCP), and national/local regulations. Exclusion criteria: Other synchronous metastatic lesions. Patients may be included if they have had curative resection of metastatic CRC disease more than 2 years prior to inclusion and have no relapse at this location is detected. History of prior other malignant disease the last 3 years, except for adequately treated carcinoma of the cervix or basal or squamous cell skin cancer. History of central nervous system (CNS)- or bone metastases Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina, or serious cardiac arrhythmia History of any liver disease including Hepatitis B or C infection Chemotherapy/radiation therapy or major surgery within the last 4 weeks before start of treatment BMI > 35 Pregnant or breast-feeding patients Alcohol or drug abuse Use of drugs that can influence hepatic function (e.g. phenytoin or phenobarbital) Use of anticoagulants Any reason why, in the opinion of the investigator, the patient should not participate in the study protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MOC31PE Immunotoxin<br>Drug to be instilled on day 1 after cytoreductive surgery and HIPEC. | Drug: MOC31PE Immunotoxin<br>* Patients who meet inclusion criteria will be treated with a single intraperitoneal MOC31PE immunotoxin instillation for 6 hours on the first day after CRS and HIPEC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | Follow-up: 5 years from administration of study drug, or until disease progression | 5 years or until disease progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax, Tmax | Measurements will be done at 0, 3, 6, 12, 24, 48 and 72 hours after administration of study drug | 8 weeks | 
| Neutralizing anti-immunotoxin antibody response | Measurements of neutralizing anti-immunotoxin antibody response will be done at 4 and 8 weeks after administration of study drug | 8 weeks | 
| Biomarkers of disease recurrence | Serum samples for identification of biomarkers of disease recurrence will be taken at every follow-up for 5 years or until disease progression | 5 years or until disease progression | 
| Overall survival | Overall survival of all patients will be assessed after 5 years | 5 years | 
| Disease free survival | Follow up period of 5 years, or until disease progression | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peritoneal Carcinomatosis, Peritoneal Metastasis, Colorectal Cancer, Cytoreductive surgery, HIPEC, Intraperitoneal treatment, Immunotoxin, MOC31PE