The UNCOVER study is a longitudinal observational cohort focused on patients at high risk for cancer cachexia. At Kaiser Permanente Northern California, up to 800 individuals with advanced or unresectable non-small cell lung cancer, pancreatic adenocarcinoma, or colorectal cancer will be enrolled, as these malignancies carry a substantial risk of cancer cachexia, which is characterized by progressive loss of weight, muscle, and adipose tissue, accompanied by functional decline and reduced quality of life. Data collected includes demographic, physiologic, and clinical data, including tumor characteristics and biomarkers of inflammation, hormonal and metabolic status, body composition, physical function, and patient reported outcomes. Investigators will identify patient phenotypes (i.e., subgroups) that may reflect distinct biological or clinical pathways underlying cancer cachexia. By characterizing heterogeneity in cancer cachexia, this study aims to inform the development of improved diagnostic criteria and more targeted therapeutic strategies, ultimately enhancing clinical trial design and supportive care for patients with advanced colorectal, lung, or pancreatic cancer.
Have a primary diagnosis of unresectable or Stage IV 1) non-small cell lung cancer (NSCLC), 2) pancreatic adenocarcinoma, or 3) colorectal cancer (CRC).
Plan to start first line systemic anti-cancer therapy (chemotherapy, immunotherapy, targeted therapy) in the next 6 weeks or has started first-line systemic therapy in the previous 6 weeks.
Have an an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
Be able to understand, speak and read English.
Have contraindications to physical function assessments (30-second bicep curl, Timed-Up-And-Go test, or 30-Second Sit to Stand test) per the treating provider or their designee.
Have any planned major surgeries within the next 3 months after enrollment to the best knowledge of the investigator/treating provider or their designee.
Have received chemotherapy or surgery for separate primary cancer within the past 3 years other than non-melanoma skin cancer.
Be pregnant or within 6 months postpartum.
Patients undergoing treatment for non-small cell lung cancer (NSCLC), pancreatic adenocarcinoma, or colorectal cancer.
Cohort
Prospective
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood and archived tumor samples. A sub-sample undergo collection of stool samples.
Computed Tomography
Procedure/SurgeryUndergo CT or PET/CT scan
Electronic health record review
Other interventionElectronic Health Record Review
Medical Device Usage and Evaluation
Other interventionWear actigraph
Physical functions assessments
Other interventionUndergo physical function assessments including 30-second bicep curl, timed up and go (TUG), and 30-second sit to stand
Positron Emission Tomography (PET)
Procedure/SurgeryUndergo PET/CT scan
Survey Administration
Other interventionComplete surveys
Multiple distinct diagnostic cancer cachexia phenotypes
Phenotypes will be based on patient-reported symptoms, physical activity and function assessments, biomarkers, and body composition measured longitudinally using latent class analysis and other clustering methods.
Overall survival: time to death
Time to death will be assessed as the interval between phenotype ascertainment and death from any cause. Participants without a recorded death event will be censored at the end of available follow-up (e.g., end of health plan membership or the study observation period).
Functional decline
Associations between each cancer cachexia phenotype and functional decline is a secondary outcome. Functional status will be measured at baseline and study completion by physical function assessments and patient-reported questionnaires.
Treatment intolerance
Treatment intolerance will be modeled as time to event outcomes. Treatment data including chemotherapy, targeted therapy, and immunotherapy will be obtained from the electronic medical record.
Early predictors of decline
Logistic regression will be used to identify patient characteristics apparent at clinical presentation that are early predictors of each cancer cachexia phenotype, focusing on the high-risk phenotypes that are associated with poor outcomes.
Click on the lead sponsor to view all of their trials.
Kaiser Permanente
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Cancer Research UK
Collaborator
