Non-invasive Imaging of Cetuximab-Zr. 89 Uptake Wit PET: a Phase I Trial in Stage IV Cancer Patients (Cetuximab Zr89)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Maastricht Radiation Oncology
Sponsor:
Collaborator:
VU University Medical Center
Information provided by (Responsible Party):
Maastricht Radiation Oncology
ClinicalTrials.gov Identifier:
NCT00691548
First received: June 2, 2008
Last updated: October 23, 2014
Last verified: October 2014

June 2, 2008
October 23, 2014
June 2009
December 2014   (final data collection date for primary outcome measure)
Toxicity (CTCAE 3.0) [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00691548 on ClinicalTrials.gov Archive Site
Image Quality (Tumour-to-Background Ratio) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Non-invasive Imaging of Cetuximab-Zr. 89 Uptake Wit PET: a Phase I Trial in Stage IV Cancer Patients
Non Invasive Imaging of Cetuximab-Zirconium-89 Uptake With PET: a Phase I Trial in Stage IV Cancer

Non invasive imaging of cetuximab uptake with PET could help to select the patients who could be treated by cetuximab, a registered but expensive monoclonal antibody against EGFR. Other monoclonal antibodies labelled with Zirconium-89 have already been used with success in patients. The combination of cetuximab labelled with Zirconium-89 is a promising new probe to determine cetuximab uptake, which has been tested in various pre-clinical animal models in Maastricht with excellent results.

We propose a two step study design (see figure 1). As our ultimate goal for the future is to determine the uptake of 89Zr-cetuximab in the tumour before and during therapy, we need to investigate the toxicity of two consecutive low doses of 89Zr-cetuximab in the first place. However, as in future studies and in some patients, it is also possible that a single, larger dose of 89Zr-cetuximab is needed to obtain the best image quality, we will also investigate the toxicity of a single larger dose.

Step 1: Determination of the toxicity of two low doses of 89Zr-cetuximab In three patients a standard loading dose of 400 mg/m2 of cetuximab will be administered, partly labelled with 89Zr (60 MBq, 2.5mg) on day 0.

On day 14, a second injection with dose of 250 mg/m2 of cetuximab, partly labelled with 89Zr (60 MBq, 2.5mg), will be given.

Step 2: Determination of the toxicity of one larger dose of 89Zr-cetuximab A standard loading dose of 400 mg/m2 of cetuximab will be administered in 3 patients, a part labelled with 89Zr (120MBq, 5mg).

Toxicity will be scored twice a week from the day of first injection (day 0) up to day 14, according to the CTCAE3.0 scoring system. As after 14 days, the activity of Zr89 is low (four half-lives of Zr89 is 4 x 3.2 days = 12.8 days), no additional toxic effect is expected. Blood sampling will be done weekly (haematology, liver and kidney function).

When in 0/3 patients a toxicity of grade 3 or more has occurred step 2 is considered safe. If in 1/3 patients a grade 3 has occurred, 3 more patients will be included in this step. If another grade 3 toxicity occurs in 1/3 patients, the study will be stopped. When at maximum 1/6 patients experience a grade 3 toxicity, this step will be considered safe. When step 2 is considered safe, the study is ended.

After the injection, visualization of all tumour sites will be analyzed by performing a PET-CT scan on day 4, 5 and 6 post injection. An additional scan on day 3 or 7 is optional.* At day 5 post injection a perfusion PET-CT will be performed.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Stage IV Cancer
Drug: Cetuximab-Zr. 89

Step 1: Determination of the toxicity of two low doses of 89Zr-cetuximab In three patients a standard loading dose of 400 mg/m2 of cetuximab will be administered, partly labelled with 89Zr (60 MBq, 2.5mg) on day 0.

On day 14, a second injection with dose of 250 mg/m2 of cetuximab, partly labelled with 89Zr (60 MBq, 2.5mg), will be given.

Step 2: Determination of the toxicity of one larger dose of 89Zr-cetuximab A standard loading dose of 400 mg/m2 of cetuximab will be administered in 3 patients, a part labelled with 89Zr (120MBq, 5mg).

Experimental: 1
Intervention: Drug: Cetuximab-Zr. 89
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
12
December 2014
December 2014   (final data collection date for primary outcome measure)

Inclusion criteria:

  • Stage IV cancer (primary or recurrent)
  • Normal white blood cell count and formula
  • Normal platelet count
  • No anemia requiring blood transfusion or erythropoietin
  • Adequate hepatic function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for the institution; ALT, AST, and alkaline phosphatase ≤ 2.5 x ULN for the institution).
  • Calculated Creatinin clearance at least 60 ml/min
  • No previous administration of cetuximab
Both
18 Years and older
No
Contact: Dirk De Ruysscher, Dr. 31-88-445-5666 dirk.deruysscher@maastro.nl
Netherlands
 
NCT00691548
Cetuximab-Zr.89 fase I, 08-3-039 (MEC)
Yes
Maastricht Radiation Oncology
Maastricht Radiation Oncology
VU University Medical Center
Principal Investigator: Dirk De Ruysscher, Dr. Maastro Radiation Oncology
Maastricht Radiation Oncology
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP