Project title: New strategies to improve drug development for carcinoid tumors

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General Description

Incorporating serial blood samples and CT scan images from a recently clinical trial, a team of investigators from around the country will explore new approaches to monitoring response: evaluation of multiple proteins in circulating blood, and computational analysis of CT images. This very novel work could lead to the identification of better ways of assessing treatment effects, facilitating testing of the next generation of therapeutic agents in NETs.

Outcomes:

We published the results of A021202, a randomized, double-blind, phase II trial of pazopanib versus placebo in patients with progressive advanced extrapancreatic neuroendocrine tumors (epNETs) in October 2025. (PMID 40902132). Treatment with pazopanib significantly delayed tumor growth compared to placebo. However, treatment with pazopanib was associated with more toxicity, with more deaths and more patients in the pazopanib arm going off study drug for side effects. Taken together, the data suggests that pazopanib slows epNET growth, but at the expense of toxicity; additional information is needed to determine which patients are most likely to benefit and least likely to suffer serious side effects from the drug.

On-study and pre-enrollment CT/MRI scan images for A021202 patients were transferred from the ALLIANCE Imaging Core Laboratory (Ohio State University) to our collaborating center for analyses of images. Collection of information about tumor volume and special radiologic features present in CT images, but not visible to the naked eye (also known as “radiomic features”) was performed (initially delayed due to Covid-19 pandemic due to resultant staffing and remote workflow changes). Ultimately, we identified an AI-based radiomic signature that merges conventional CT features (at baseline and early follow-up) with clinical characteristics to identify two groups with markedly different survival in patients with advanced ep-NETs treated in A021202. An analysis of linking blood proteins in serial blood samples with clinical outcomes is in process. In addition, our preliminary data confirm that traditional assessment of tumor response by imaging in A021202 was challenging, with central readers and local radiologists frequently disagreeing about when tumor progression occurred (potentially leading to both over-treatment and under treatment of patients). The manuscript describing our findings and recommendations regarding discordance (and the value of central confirmation) is in preparation.

Our ultimate goal is to accelerate the discovery of more effective treatments for patients with NETs by identifying novel clinical trial designs that incorporate improved selection of patients and better endpoints for measuring and tracking response to therapy. We believe that the findings from our analysis of A021202 imaging and angiome profiling data can be validated in the completed CABINET study (phase III trial of cabozantinib vs placebo in epNET and pancreas NET; J Chan, PI) and will inform future clinical trial design for NETs and selection of endpoints.

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