Colorectal Neoplasms
Conditions
Keywords
Peritoneal Carcinomatosis, Peritoneal Metastasis, Colorectal Cancer, Cytoreductive surgery, HIPEC, Intraperitoneal treatment, Immunotoxin, MOC31PE
Brief summary
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
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.
Interventions
DRUGMOC31PE Immunotoxin
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
Sponsors
Oslo University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | 5 years or until disease progression | Follow-up: 5 years from administration of study drug, or until disease progression |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax, Tmax | 8 weeks | Measurements will be done at 0, 3, 6, 12, 24, 48 and 72 hours after administration of study drug |
| Neutralizing anti-immunotoxin antibody response | 8 weeks | Measurements of neutralizing anti-immunotoxin antibody response will be done at 4 and 8 weeks after administration of study drug |
| Biomarkers of disease recurrence | 5 years or until disease progression | Serum samples for identification of biomarkers of disease recurrence will be taken at every follow-up for 5 years or until disease progression |
| Overall survival | 5 years | Overall survival of all patients will be assessed after 5 years |
| Disease free survival | 5 years | Follow up period of 5 years, or until disease progression |
Countries
Norway
Outcome results
None listed