The aim of the present study is to investigate whether a 4 hr time lapse between the first dose of pemetrexed in NSCLC is associated with increased FLT uptake, in responding patients.
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change of 18F-FLT uptake as measured with time lapse of 4 hrs after pemetrexed.
18F-FLT changes versus clinical response measured with RECIST.
Secondary outcome
Not applicable
Background summary
Thymidylate synthase is a key enzyme for de novo synthesis of DNA and as such a
target for anticancer drug development. In a mouse model (fibrosarcoma) it has
been shown that 3'-deoxy-3'-[(18)F]fluorothymidine (18F-FLT) positron emission
tomography (PET) allows for early measurement of thymidylate synthase
inhibition effectuated by 5-FU (Perumal M, Cancer Res 2006): effective
TS-inhibition resulted in a 1.8 fold increase of 18F-FLT cellular uptake.
Hence, 18F-FLT PET appears suited for noninvasive assessment of thymidylate
synthase inhibition in tumours.
Conceptually, 18F-FLT PET could thus be used to predict the efficacy of
pemetrexed, amongst others an inhibitor of TS, in non-small cell lung cancer
(NSCLC) therapy.
Pemetrexed has several side-effects such as nausea, anemia, bone marrow
depression, stomatitis, pharyngitis, rash. This unnecessary toxicity in
non-responding patients might be strongly reduced if effectiveness would be
predictable, e.g. from PET measurements.
Study objective
The aim of the present study is to investigate whether a 4 hr time lapse
between the first dose of pemetrexed in NSCLC is associated with increased FLT
uptake, in responding patients.
Study design
Single centre, prospective observational study including 12 eligible patients
with NSCLC (tumor size at least 3 cm) who will be scanned with 18F-FLT PET on
two separate occasions: first within 7 days prior to pemetrexed therapy, the
second 4 hrs after the first therapeutic dose of pemetrexed. Personal
characteristics will be registered, (age, sex, bodyweight, height, drug use).
The standard follow-up measurements (CT scan, laboratory tests) will be
performed every 6 weeks after the first therapeutic dose of pemetrexed.
Study burden and risks
The total amount of blood taken for investigation is 120 ml. The total amount
of radiation burden: 10 mSv.
Postbus 7057
1007 MB Amsterdam
Nederland
Postbus 7057
1007 MB Amsterdam
Nederland
Listed location countries
Age
Inclusion criteria
Patient age 18 years or older
Histological diagnosis of NSCLC
Scheduled for treatment with pemetrexed
Tumour diameter min. 3cm (to minimize partial volume effects) within the chest
Able to remain supine for 60 minutes
Written informed consent
Exclusion criteria
Pregnant or lactating patients
Claustrophobia
Patients having metal implants (e.g. pacemakers)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL23639.029.08 |