Intravenous BIBH 1 in Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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Study to evaluate the anti-tumour activity, safety and pharmacokinetics of unlabelled sibrotuzumab administered weekly (seven days +/- one day) at a dose of 100 mg (a total of 12 administrations) in patients with metastatic colorectal cancer.

Official Title
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A Phase II Uncontrolled Sudy to Evaluate the Antitumour Activity and Safety of Intravenous BIBH 1, Administered in a Weekly Dose of 100 mg in 12 Weeks, in Patients With Metastatic Colorectal Cancer

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Drug: BIBH 1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with metastatic colorectal cancer International Union Against Cancer (UICC) Stage IV who are progressive under at least two previous chemotherapy regimes or who refused conventional treatment or who are not eligible for conventional treatment Progressive disease documented by subsequent computed tomography (CT) or magnetic resonance imaging (MRI) scanning prior to study entry. The last CT or MRI scans must be performed within 1 month before study entry. The first CT or MRI scan should be conducted within 6 months before study entry Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 Expected survival of ≥ 6 months Greater than or equal to 18 years of age Platelet count ≥ 100 x 10**9/L Total leukocytes ≥ 2500/mm**3 Alanine aminotransferase/Aspartate aminotransferase (ALT/AST) ≤ 4 x upper limit of normal Total bilirubin ≤ 2.0 mg/dl (or 34µmol/L, Systeme International (SI) unit equivalent) Serum creatinine ≤ 2.0 mg/dl (0.20 mmol/l) Written informed consent in accordance with Good Clinical Practice and local legislation Exclusion Criteria: Active metastatic disease to the central nervous system, exhibited by new or enlarging lesions on CT or MRI scan or within 3 months of treatment (i.e., surgery or radiotherapy) for brain metastases Exposure to an investigation agent within 30 days prior to the first BIBH 1 infusion Patients who are not fully recovered from surgery (incomplete healing) Chemotherapy or immunotherapy within 30 days prior to the first BIBH 1 infusion Radiation therapy to the symptomatic sites included for tumour measurements within 30 days prior to study entry Previous administration of a murine, chimeric or humanised measurement and/or antibody fragment (e.g. BIBH 1, Panorex) Serious illness: e.g., active infections requiring antibiotics, bleeding disorders, patients with known untreated or unstable coronary heart disease (e.g. unstable angina or myocardial infarction within 6 months prior to study entry) or diseases considered by the investigator to have potential for interfering with obtaining accurate results from this study Women who are breast-feeding or pregnant Men and women of childbearing potential who are unwilling to utilise a medically acceptable method of contraception Patients who suffer from autoimmune diseases

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: BIBH 1<br> | Drug: BIBH 1<br>* 100 mg/week<br>* Other names: Sibrotuzumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-tumour response |  | 4 weeks after the last administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to tumour progression |  | up to 16 weeks | 
| Time to loss of response |  | up to 16 weeks | 
| Disease progression-free survival time |  | up to 16 weeks | 
| Changes in titers of human anti-human antibody (HAHA) |  | up to 16 weeks | 
| Incidence and intensity of adverse events graded by Common toxicity criteria (CTC) |  | up to 16 weeks | 
| Assessment of the maximum toxicity grade observed for each patient |  | up to 16 weeks | 
| Frequency of on-study deaths |  | up to 16 weeks | 
| Maximum drug concentration (Cmax) |  | up to 16 weeks | 
| Minimum drug concentration (Cmin) |  | up to 16 weeks | 
| Area under the concentration-time curve (AUC) |  | up to 16 weeks | 
| Total serum clearance (CL) |  | up to 16 weeks | 
| Volume of distribution at steady state (Vss) |  | up to 16 weeks | 
| Terminal half-life (t1/2) |  | up to 16 weeks | 
| Mean residence time (MRT) |  | up to 16 weeks |