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

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).

Study Overview

• Status: Completed
• Conditions: Stage IV Cancer
• Intervention / Treatment: Drug: Cetuximab-Zr. 89

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 Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands, 6229 ET
    • Maastro Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Toxicity (CTCAE 3.0)	2 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Image Quality (Tumour-to-Background Ratio)	4 weeks

Collaborators and Investigators

• Sponsor: Maastricht Radiation Oncology
• Collaborators: Amsterdam UMC, location VUmc
• Investigators: Principal Investigator: Dirk De Ruysscher, Dr., Maastro Radiation Oncology

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: June 2, 2008
• First Submitted That Met QC Criteria: June 4, 2008
• First Posted (Estimate): June 5, 2008

Study Record Updates

• Last Update Posted (Estimate): April 10, 2015
• Last Update Submitted That Met QC Criteria: April 9, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Stage IV cancer
• Additional Relevant MeSH Terms: Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: Cetuximab-Zr.89 fase I; 08-3-039 (MEC)