Advanced Colorectal Carcinoma, Advanced Lung Non-Small Cell Carcinoma, Advanced Pancreatic Adenocarcinoma, Stage IV Colorectal Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8, Unresectable Colorectal Carcinoma, Unresectable Lung Non-Small Cell Carcinoma
Conditions
Keywords
Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Colonic Diseases, Intestinal Diseases, Rectal Diseases, Respiratory Tract Neoplasms, Thoracic Neoplasms, Lung Diseases, Respiratory Tract Diseases, Endocrine Gland Neoplasms, Pancreatic Diseases, Endocrine System Diseases, Colorectal Neoplasms, Lung Neoplasms, Pancreatic Neoplasms, Clinical Laboratory Techniques, Diagnostic Techniques and Procedures, Diagnosis, Investigative Techniques, Heart Function Tests, Diagnostic Techniques, Cardiovascular, Respiratory Function Tests, Diagnostic Techniques, Respiratory System, Specimen Handling, Exercise Test
Brief summary
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.
Detailed description
PRIMARY OBJECTIVES: I. To identify multiple distinct diagnostic phenotypes within the syndrome of cancer cachexia as defined by host characteristics (e.g. cachexia symptoms, physical activity, physical function, blood biomarkers, and body composition) at baseline and change in these factors over time in patients with cancer at high risk for cancer cachexia. II. To determine the association of each cancer cachexia phenotype with overall survival. SECONDARY OBJECTIVES: I. To determine the association of each cancer cachexia phenotype with functional decline and treatment intolerance. II. To inform clinical practice guidelines for prompt recognition of patients likely to progress to refractory cachexia, identify early predictors apparent at clinical presentation of each cancer cachexia phenotype defined in the primary objective.
Interventions
PROCEDUREBiospecimen Collection
Undergo collection of blood and archived tumor samples. A sub-sample undergo collection of stool samples.
PROCEDUREComputed Tomography
Undergo CT or PET/CT scan
OTHERElectronic health record review
Electronic Health Record Review
OTHERMedical Device Usage and Evaluation
Wear actigraph
OTHERPhysical functions assessments
Undergo physical function assessments including 30-second bicep curl, timed up and go (TUG), and 30-second sit to stand
PROCEDUREPositron Emission Tomography (PET)
Undergo PET/CT scan
OTHERSurvey Administration
Complete surveys
Sponsors
Kaiser Permanente
National Cancer Institute (NCI)
Cancer Research UK
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a primary diagnosis of unresectable or Stage IV 1) non-small cell lung cancer (NSCLC), 2) pancreatic adenocarcinoma, or 3) colorectal cancer (CRC). Note: Patients do not need to have cachexia to be eligible * 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. Note: Patients who received systemic anti-cancer therapy previously as part of adjuvant or neoadjuvant therapy and have since recurred are still eligible if such treatment was longer than 6 months prior to enrollment. * Have an an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. * Be able to understand, speak and read English. * Be 18 years or older
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Multiple distinct diagnostic cancer cachexia phenotypes | Baseline through study completion, assessed up to 1 year follow up | 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 | Baseline to death (the event) or the last contact (censored), assessed up to 1 year follow up | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functional decline | Baseline through study completion, assessed up to 1 year follow up | 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 | Baseline through study completion, assessed up to 1 year follow up | 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 | Baseline through study completion, assessed up to 1 year follow up | 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. |
Countries
United States
Contacts
CONTACTElizabeth M Cespedes Feliciano, ScD, SM
CONTACTMichelle C Ross, MPH
Outcome results
None listed