Primary objectives* 18F-FLT-PET/CT: - To correlate the percentage change in SUV between baseline (SUV-1) and early therapy (SUV-2) with pathological quantification (% of viable tumor cells) of the primary tumor after pre-operative chemotherapy in…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Percentage of ADC change at day 14 (i.e. ADC-2) relative to baseline (i.e.
ADC-1)
* Percentage of FLT uptake change at day 14 (i.e. SUV-2) relative to baseline
(i.e. SUV-1)
* Pathological quantification (% viable tumor cells) measured in surgical
specimens
Secondary outcome
* Pre-operative (post-treatment) ADC measurement (i.e. ADC-3)
* Pre-operative (post-treatment) FLT uptake measurement (i.e. SUV-3)
* Tumor volume (baseline and pre-operative) measured by CT or MRI
* Immunohistochemistry (IHC) of cell proliferation marker Ki-67-index in
diagnostic biopsy samples (if available) and surgical specimens.
* Metabolic change in FDG-PET (baseline and pre-operative, if available)
* Safety
Background summary
Response assessment in NSCLC is usually performed according to CT scans of the
thorax. Vigorous debate has challenged the use of anatomic assessments alone
such as conventional CT and MRI, as it may take two or three months to detect
any tumor shrinkage. In addition, it has been observed that changes in tumor
metabolism are more significant than anatomical changes in lung cancer
patients. Thus only morphological information may not be a suitable tool to
assess early treatment response. Furthermore with the development of targeted
chemotherapy agents, which are primarily cytostatic, methods of assessing the
biological response of a tumor becomes increasingly relevant, because reduction
in tumor size will not always be expected and conventional imaging will not
suffice.
Therefore, there is an unmet need for methods assessing therapeutic
effectiveness by criteria other than morphological measurements. In this
regard, early tumor response assessment imaging biomarkers that quantify cell
proliferation by 18[F]-fluorothymidine (18F-FLT) using PET and cell death by
apparent diffusion coefficient (ADC) using diffusion weighted magnetic
resonance imaging (DWI-MRI), could together provide a more detailed insight
into a tumor*s microenvironment. In previous studies it was proven that the
percentage of viable tumor cells in pathological evaluation is a significant
predictor of OS and disease free survival (DFS) in NSCLC patients treated with
preoperative chemotherapy. In this study we want to evaluate 18F-FLT uptake and
ADC as predictive imaging biomarkers of cell proliferation and cell death,
respectively, using histopathology as the reference test.
Study objective
Primary objectives
* 18F-FLT-PET/CT:
- To correlate the percentage change in SUV between baseline (SUV-1) and early
therapy (SUV-2) with pathological quantification (% of viable tumor cells) of
the primary tumor after pre-operative chemotherapy in patients with operable
NSCLC.
* DWI-MRI:
- To correlate the percentage change in ADC between baseline (ADC-1) and early
therapy (ADC-2) with pathological quantification (% of viable tumor cells) of
the primary tumor after pre-operative chemotherapy in patients with operable
NSCLC.
2.2 Secondary objectives
* 18F-FLT-PET/CT:
- To demonstrate correlation between pre-operative SUV (SUV-3) and tumor
proliferation marker Ki67 index in NSCLC.
- To compare the changes of SUV (SUV-3 vs. SUV-1; SUV-2 vs. SUV-1) to changes
in tumor size from anatomic imaging (CT/MRI).
- To compare the changes of SUV (SUV-3 vs. SUV-1; SUV-2 vs. SUV-1) to metabolic
changes from 18F-FDG-PET, if available.
* DWI-MRI:
- To compare the changes of ADC (ADC-3 vs. ADC-1; ADC-2 vs. ADC-1) to changes
in tumor volume from anatomic imaging (CT/MRI).
- To compare the changes of ADC (ADC-3 vs. ADC-1; ADC-2 vs. ADC-1) to metabolic
changes from 18F-FDG-PET, if available.
* Both 18F-FLT-PET/CT and DWI-MRI:
- To demonstrate correlation between ADC and SUV at the same time point.
Study design
This is a prospective, multicenter, single-arm imaging trial. Patients with
NSCLC will undergo 18F-FLT-PET/CT and DWI-MRI scans on three separate
occasions: at baseline, at 14 days (maximum +/- 1 days deviation is acceptable)
after first administration of chemotherapy and finally after up to 4 cycles of
chemotherapy. Dedicated in-house developed software will be used to quantify
18F-FLT SUV and ADC to assess tumor characteristics and response to therapy.
And these measures will be compared to pathological quantifications of the
primary tumor performed after resection.
Study burden and risks
A PET scan is a regular diagnostic imaging technique. Each study will be
performed in complance with the radiation safety guidelines of the department.
The total radiation dose will be 20.4 mSv. To compare, every person living in
the Netherlands receives a natural background doses of 2-2.5mSv per year.
Although the extra dose is relatively high we think that it is acceptable for
this particular study in view of this specific population and high scientific
impact. The 5-year overall survival rates for stage II and IIIA disease is 30%
and 20% respectively, whereas the possible hazard of cancer induction by
radiation is small and only after several years (>10 years). In addition the
results of this study will have great clinical benefit in improving
personalized therapy stragies for cancer patients. Cannulation of the venous
canulla will be performed by experienced clinicians of the Department of
radiology and nuclear medicine. In spite of this, occasionally these cannulae
may cause a hematoma. Druing the study a maximum of 30 mL is taken (10 mL per
FLT-scan).
Avenue E. Mounierlaan 83/11
Brussel 1200
BE
Avenue E. Mounierlaan 83/11
Brussel 1200
BE
Listed location countries
Age
Inclusion criteria
* Age >= 18 years
* WHO performance status 0-1
* Histologically or cytological confirmed clinical stage II-IIIA non-small cell lung carcinoma (NSCLC), according to 7th TNM classification (NOTE: patients with resectable N2 disease are also eligible)
* Baseline standard imaging assessment & staging should be performed within 6 weeks prior to planned treatment start.
* Patients must be candidate for curative intent surgery, and must be expected to complete the treatment.
* No prior or current anticancer treatment for NSCLC, pre-operative therapy will include only chemotherapeutic drugs (pemetrexed is contraindicated), no other biological, targeted or radiotherapy is allowed
* No treatment with any investigational drug substance within 4 weeks prior to registration.
* No other malignancies in the 3 years prior to study entry with the exception of surgically cured carcinoma in situ of the cervix, in situ breast cancer, incidental finding of stage T1a or T1b prostate cancer, and basal/squamous cell carcinoma of the skin
* No evidence of any medical condition which would impair the ability of the patient to participate in the trial or might preclude therapy with chemotherapeutic drugs according to routine medical practice (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease, known dihydropyrimidine dehydrogenase deficiency, active infection, uncontrolled diabetes mellitus; uncontrolled arterial hypertension, history of unstable myocardial infarction)
* Adequate hematology and biochemical investigations, (should be done maximum 6 weeks before treatment starts)
* Normal bone marrow function based on routine blood samples, i.e. neutrophils >= 1.5 x 109/L, platelets >= 75 x 109/L, hemoglobin >= 10.0 g/dL
* Normal kidney function creatinine clearance >= 60 mL/min,
* Normal liver function assessed by routine laboratory examinations, i.e. bilirubin < 1.5 x upper limit of normal (ULN), ALT< 3 x ULN
* Patients must not have any contraindication for 18F-FLT-PET/CT or MRI procedures.
* Patient primary lung tumor larger than 20 mm in diameter (measured by diagnostic CT or MRI).
* Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test before trial registration.
* Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last study procedure. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.
* Female subjects who are breast feeding should discontinue nursing before trial registration.
* Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before randomization in the trial.
* Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.
Exclusion criteria
- Does not meet the inclusion criteria
- Younger than 50 years
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 | NL51780.029.14 |