Clinical trial NCT00860860: Study of Pretargeted Radioimmunotherapy of a Anti-CEA Bispecific Antibody and Lu177-labeled Peptide in Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Colorectal Neoplasms
Keywords: radioimmunotherapy
pretargeting
bispecific antibody
lutetium 177
phase I clinical trial
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2009-03-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Toxicity defined by NCI Common Terminology Criteria for Adverse Events version 3.0
timeFrame: first three weeks: daily, thereafter: weekly
Secondary outcomes:
measure: 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
timeFrame: Pk/biodistr: first week after administration; imaging: first 5 days after administration of IMP-288-In111; tumor respone: every 8 weeks
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
Study officials:
affiliation: RUNMC Department of Nuclear Medicine
name: O C Boerman, PhD
role: STUDY_CHAIR
affiliation: RUNMC Department of Nuclear Medicine
name: R Schoffelen, MD
role: STUDY_CHAIR
affiliation: RUNMC Department of Nuclear Medicine
name: W JG Oyen, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: RUNMC Department of Medical Oncology
name: W TA van der Graaf, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: