Immunotoxin in Peritoneal Carcinomatosis- ImmunoPeCa Trial

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

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).

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.

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