Study of Pretargeted Radioimmunotherapy of a Anti-CEA Bispecific Antibody and Lu177-labeled Peptide in Colorectal Cancer

Study Overview
=================
Brief Summary
-----------------
This study will investigate the toxicity, safety and pharmacokinetics of pretargeted radioimmunotherapy with anti-CEA x anti-hapten bispecific antibody TF2 and Lu-177-labeled di-HSG-DOTA peptide IMP-288. Furthermore, the sensitivity of pretargeted imaging with In-111-labeled IMP-288 as compared to standard methods of tumor detection, and the preliminary efficacy of the therapy.

Detailed Description
-----------------
Pretherapy cycle with IMP-288 labeled In111.

Official Title
-----------------
Phase I Clinical Study of the Feasibility of Pretargeted Radioimmunotherapy of an Anti-CEA Bispecific Antibody and Lu-177-labeled Peptide in Patients With Advanced Colorectal Cancer

Conditions
-----------------
Colorectal Neoplasms

Intervention / Treatment
-----------------
* Drug: TF2
* Drug: IMP-288 labeled with In111 and Lu177


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with CEA expressing advanced colorectal tumors for which no standard treatment is available WHO performance status: 0 or 1 Having normal hematological function: Neutrophils > 1.5 x 109/l; Platelet count > 150 x 109/l, without transfusion during the previous month; Hemoglobin > 5.6 mmol/l Total bilirubin < 2 x upper limit of normal (ULN) ASAT, ALAT < 3 x ULN Serum creatinine < 2 x ULN Cockcroft clearance > 50 ml/min Negative pregnancy test for women of child¬bearing potential (urine or serum) Age over 18 years Ability to provide written informed consent Exclusion Criteria: Known metastases to the brain Chemotherapy, external beam radiation or immunotherapy within 4 weeks prior to study. Limited field external beam radiotherapy to prevent pathological fractures is allowed, when unirradiated, evaluable lesions elsewhere are present. Prior angiogenesis inhibitors within 4 weeks; bevacizumab within 8 weeks Cardiac disease with New York Heart Association classification of III or IV Patients who are pregnant, nursing or of reproductive potential and are not practicing an effective method of contraception Any unrelated illness, e.g. active infection, inflammation, medical condition or laboratory abnormalities, which in the judgement of the investigator will significantly affect patients' clinical status Life expectancy shorter than 6 months.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: TF2|TF2: 75-300 mg|
|Drug: IMP-288 labeled with In111 and Lu177|IMP-288: 100 microgram|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity defined by NCI Common Terminology Criteria for Adverse Events version 3.0 |  | first three weeks: daily, thereafter: weekly | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetics and biodistribution of TF2 and Lu-177-labeled IMP-288, sensitivity of pretargeted imaging with In-111-labeled IMP-288, and tumor response using RECIST criteria |  | Pk/biodistr: first week after administration; imaging: first 5 days after administration of IMP-288-In111; tumor respone: every 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
radioimmunotherapy, pretargeting, bispecific antibody, lutetium 177, phase I clinical trial