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

Sponsor

Maastricht Radiation Oncology (Other)

Overall Status

Completed

CT.gov ID

NCT00691548

Collaborator

Amsterdam UMC, location VUmc (Other)

Enrollment

Location

Arm

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

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).

Condition or Disease	Intervention/Treatment	Phase
Stage IV Cancer	Drug: Cetuximab-Zr. 89	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

9 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Non Invasive Imaging of Cetuximab-Zirconium-89 Uptake With PET: a Phase I Trial in Stage IV Cancer

Study Start Date :

Jun 1, 2009

Actual Primary Completion Date :

Mar 1, 2015

Actual Study Completion Date :

Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	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).

Arm

Intervention/Treatment

Experimental: 1

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).

Outcome Measures

Primary Outcome Measures

Toxicity (CTCAE 3.0) [2 weeks]

Secondary Outcome Measures

Image Quality (Tumour-to-Background Ratio) [4 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maastro Clinic	Maastricht		Netherlands	6229 ET

Sponsors and Collaborators

Maastricht Radiation Oncology
Amsterdam UMC, location VUmc

Investigators

Principal Investigator: Dirk De Ruysscher, Dr., Maastro Radiation Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Maastricht Radiation Oncology

ClinicalTrials.gov Identifier:

NCT00691548

Other Study ID Numbers:

Cetuximab-Zr.89 fase I
08-3-039 (MEC)

First Posted:

Jun 5, 2008

Last Update Posted:

Apr 10, 2015

Last Verified:

Apr 1, 2015

Keywords provided by Maastricht Radiation Oncology

Stage IV cancer

Additional relevant MeSH terms:

Cetuximab

Study Results

No Results Posted as of Apr 10, 2015