Study of MOC31-PE in Antigen Positive Carcinomas

Oslo University Hospital20 enrolled

Overview

Immunotoxins (ITs), monoclonal antibodies conjugated to plant or bacterial toxins, have been extensively investigated for their possible use as anti-tumor agents although not in carcinoma patients with minimal residual disease. Various ITs have been tested in early clinical trials and recent studies demonstrate anti-tumor activity of IT treatment in patients with glioblastoma and different solid tumors. Systemic treatment with immunotoxins directed against carefully selected epithelial cell surface molecules may have a potential for eradicating also dormant metastatic tumor cells, as their action is independent of cell proliferation. The effector moieties of the IT used here, the Pseudomonas exotoxin A (PE), inhibits protein synthesis in eukaryotic cells by catalytic inactivation (ribosylation) of elongation factor 2 in the ribosome complex.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Carcinoma

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically confirm epithelial carcinoma, verified to be positive for the targeting antigen(Ep-CAM/epithelial glyco protein 2)according to the criteria given below. * Tumor specimens verified to be positive for the targeting antibody,i.e.EGP2 positive (MOC31) by immunocytochemical or histochemical staining. * Signed written informed consent * Patients with no clinically symptomatic central nervous system (CNS) involvement. * Both gender, age 18 -75 years old. * Life expectancy of at least 3 months * Eastern Cooperative Oncology Group (ECOG) Performance status 0-2 * Adequate hematologic, renal and hepatic function defined as: Neutrophils \> 1.5 x 10\^9/L;Platelets \> 100 x 10\^9/L; Creatinine \< 120 umol/L; Total bilirubin within normal range. Liver enzymes (ALAT and ASAT \<2.5 UNL: alkaline phosphatase \< 1.5 UNL and yGT \< 1.5 UNL). * Coagulation parameters (pT, PTT) within normal range. Exclusion Criteria: * No medical history of Hepatitis B or C infection * Patients must have no ECG abnormalities * Patients must not be HIV positive * Female premenopausal patients should not be pregnant (must have a negative pregnancy test prior to inclusion) and should not be lactating. * Patients must use effective contraception if of reproductive potential. * Prior chemotherapy and/or radiation should be completed for at least 4 weeks prior to study enrolment

Outcomes

Primary Outcomes

The documentation of the Maximum Tolerated Dose (MID)

Time frame: 2 years

The identification of the dose limiting toxicity (DLT)