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 April 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: April 7, 2014
Last verified: April 2014
  Purpose

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).


Condition Intervention Phase
Stage IV Cancer
Drug: Cetuximab-Zr. 89
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Maastricht Radiation Oncology:

Primary Outcome Measures:
  • Toxicity (CTCAE 3.0) [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Image Quality (Tumour-to-Background Ratio) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: June 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00691548

Contacts
Contact: Dirk De Ruysscher, Dr. 31-88-445-5666 dirk.deruysscher@maastro.nl

Locations
Netherlands
Maastro Clinic Recruiting
Maastricht, Netherlands, 6229 ET
Contact: Dirk De Ruysscher, Dr.    31-88-445-5666    dirk.deruysscher@maastro.nl   
Sponsors and Collaborators
Maastricht Radiation Oncology
VU University Medical Center
Investigators
Principal Investigator: Dirk De Ruysscher, Dr. Maastro Radiation Oncology
  More Information

No publications provided

Responsible Party: Maastricht Radiation Oncology
ClinicalTrials.gov Identifier: NCT00691548     History of Changes
Other Study ID Numbers: Cetuximab-Zr.89 fase I, 08-3-039 (MEC)
Study First Received: June 2, 2008
Last Updated: April 7, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht Radiation Oncology:
Stage IV cancer

Additional relevant MeSH terms:
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014