Principal Investigator: Wolfgang Weber, M.D.
Protocol Statistician: Constantine Gatsonis, Ph.D.
Lead Biostatistician: Lucy Hanna, MS, MAT
Lead Data Manager: Laura Hill
Project Manager: Donna Hartfeil, B.S., R.N.
Background: Several studies have suggested that positron emission tomography (PET) with the glucose analog fluorodeoxyglucose (FDG) may be used to monitor tumor response very early in the course of therapy. However, further validation is necessary before FDG-PET can be used as a new marker for tumor response in clinical trials or for the management of individual patients.
Aim: The trial aims to show that quantitative changes in FDG uptake during chemotherapy provide an early readout for the effectiveness of therapy in patients with advanced non-small cell lung cancer (NSCLC).
Rationale for validating FDG-PET in non-small cell lung cancer: To lay the foundation for quantitative FDG-PET as a potential biomarker for drug development, we have selected advanced NSCLC because it is a common disease with a poor prognosis. In the United States, more patients die of lung cancer than of breast cancer, prostate cancer, colorectal cancer, and lymphoma combined. This indicates that new tools for drug development and clinical patient management are urgently needed. From a methodological point of view, the poor prognosis of NSCLC significantly facilitates correlating tumor response in FDG-PET and patient survival, since only a relatively small patient population needs to be recruited and only a brief follow-up period is necessary. Correlating metabolic changes during chemotherapy with patient survival is the most stringent approach to validate FDG-PET as a predictive marker for treatment outcome. Another methodological consideration is that NSCLC almost universally demonstrates intense FDG uptake, which facilitates the quantitative analysis of PET studies.
Design: The trial will examine the correlation between changes in tumor FDG uptake during chemotherapy and patient survival. Furthermore, it will determine the test-retest reproducibility of quantitative measurements of tumor FDG uptake. The trial will also evaluate the time course of changes in tumor glucose metabolism during chemotherapy and measure changes in tumor FDG uptake after one and two cycles of chemotherapy, because the optimal time point to predict patient outcome by FDG-PET is currently unknown. Since it is not practical for participants to undergo a total of four (4) FDG-PET/CT scans (two prior to therapy and two during therapy), study participants will be randomized into two groups. Group A will undergo two FDG-PET/CT scans prior to chemotherapy and one FDG-PET/CT scan after the first chemotherapy cycle. Group B will undergo one FDG-PET/CT prior to chemotherapy and two FDG-PET/CT scans during therapy (after the first and second chemotherapy cycles). For both groups A and B, standard of care follow-up CT imaging after every other chemotherapy cycle will be used to determine best clinical response according to RECIST criteria.
Hypotheses: The two hypotheses underlying this trial are that (i) a metabolic response, defined as a 25% or greater decrease in peak tumor SUV post-cycle 1 of chemotherapy, provides early prediction of treatment outcome (tumor response and patient survival) and (ii) tumor glucose utilization can be measured by FDG-PET with high reproducibility.
Endpoints: The primary endpoint of this study is the prediction of one-year overall survival by monitoring the metabolic response of the tumor following one cycle of chemotherapy. Secondary endpoints are (i) the correlation between a metabolic response after one cycle of chemotherapy and subsequent best tumor response according to standard anatomic response using the RECIST evaluation criteria, (ii) correlation between a metabolic response after the first chemotherapy cycle and progression free survival, (iii) a comparison of the predictive value of FDG-PET for one-year overall survival after one and two cycles of chemotherapy, (iv) the test-retest reproducibility of standardized uptake values (SUVs).
For full protocol text and data forms, click here