LOTUS-CC: An Observational Research Study to Uncover Subtypes of Cancer Cachexia

Official title

Longitudinal Observational Trial to Uncover Subtypes of Cancer Cachexia

Overview

This study evaluates cancer-related weight and muscle mass loss, symptoms, and physical function (cachexia) in patients undergoing treatment for colorectal, lung, or pancreatic cancer that cannot be removed by surgery (unresectable) or is stage IV. Patients with these cancer types are at risk for developing cancer cachexia (CC), which is defined as weight loss, muscle loss, and fat loss due to cancer. CC has been associated with reduced physical performance, impaired quality of life, and poorer survival. Many studies that have evaluated treatments for cancer-related weight and muscle loss have aimed to treat all patients with weight loss exactly the same and, unfortunately, have not been successful. Like different cancer types, weight and muscle loss related to cancer may have different causes in different individuals and the best treatment strategy for this condition may not be a one-size-fits-all approach. Information gathered from this study may help researchers develop new diagnostic criteria for CC and design better treatments and clinical trials for cancer-related weight and muscle loss in the future to improve the quality of life in patients with advanced colorectal, lung, or pancreatic cancer.

Detailed description

PRIMARY OBJECTIVE:

I. To identify multiple distinct diagnostic subtypes within the syndrome of CC as defined by host characteristics (e.g. cachexia symptoms, physical activity, physical function, blood biomarkers including hemoglobin and albumin, and body composition) at baseline and change in these factors over time in patients with cancer at high risk for CC.

SECONDARY OBJECTIVES:

I. To determine the association of each CC phenotype with overall survival. II. To validate CC diagnostic phenotypes developed in a separate, independent cachexia observational study performed by our collaborators at Kaiser Permanente.

III. To collect human samples of blood, tumor tissue, and medical images and build a large, comprehensive CC database clinically annotated with cancer-related outcomes, cachexia symptoms, and physical function data.

EXPLORATORY OBJECTIVE:

I. To evaluate for tumor-derived factors contributing to CC by determining the association between interleukin-6 (IL-6) expression in tumor and IL-6 and CC chemokine ligand 2 (CCL2) levels in the blood in patients with CC.

OUTLINE: This is an observational study.

Patients complete surveys over 30 minutes, undergo physical function tests over 30 minutes, undergo collection of blood and archived tumor samples, and wear actigraph over 24 hours for 7 days to record daily sleep and exercise activity at baseline and 3-month follow-up. Additionally, patients undergo standard of care computed tomography (CT) or positron emission tomography (PET)/CT scans throughout the study and patients' medical records are also reviewed at baseline, 3-month and 1-year follow-up.

Interventions

• Procedure Biospecimen Collection
  Undergo collection of blood and archived tumor samples
• Procedure Computed Tomography
  Undergo CT or PET/CT scan
• Other Electronic Health Record Review
  Medical records reviewed
• Other Medical Device Usage and Evaluation
  Wear actigraph
• Other Physical Performance Testing
  Undergo physical function tests
• Procedure Positron Emission Tomography
  Undergo PET/CT scan
• Other Survey Administration
  Complete surveys

Primary outcome measures

• Identification of multiple distinct diagnostic subtypes within the syndrome of cancer cachexia (CC) [Time frame: Baseline through study completion, assessed up to 1 year follow up]

Secondary outcome measures (2)

• Association of each CC phenotype (clusters) with overall survival [Time frame: Days from registration (day 0) to death (the event) or the last contact (censored), assessed up to 1 year follow up]
• Validation of CC diagnostic phenotypes developed in a separate, independent cachexia observational study performed by collaborators at Kaiser Permanente [Time frame: Up to study completion, assessed up to 1 year]

Eligibility criteria

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

• Note: Patients do not need to have cachexia to be eligible
• Plan to start first-line systemic anti-cancer therapy (chemotherapy, immunotherapy, targeted therapy, interventional clinical trial) 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 treatment and have since recurred are still eligible if such treatment ended > 6 months prior to enrollment. Patients receiving concurrent radiation with systemic therapy or received local therapy alone (surgery, radiation therapy \[RT\]) prior to first line therapy remain eligible. Patients receiving maintenance treatment after first line therapy are not eligible
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Be able to understand, speak and read English
• Be 18 years of age or older

Exclusion criteria

• Have contraindications to physical function assessments (30-second arm curl, Timed-Up-And-Go test, or 30-second chair-stand test) per the treating provider or their designee
• Have any planned major surgeries within the next 3 months
• Have received chemotherapy or surgery for separate primary cancer within the past 3 years other than early local staged non-melanoma skin cancer
• Be pregnant

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 225 centers

• Mercy Hospital Fort Smith — Fort Smith
• Rocky Mountain Cancer Centers-Aurora — Aurora
• Boulder Community Foothills Hospital — Boulder
• Rocky Mountain Cancer Centers-Boulder — Boulder
• Rocky Mountain Cancer Centers - Centennial — Centennial
• The Women's Imaging Center — Denver
• Colorado Blood Cancer Institute — Denver
• Rocky Mountain Cancer Centers-Midtown — Denver
• … and 217 more centers

Identifiers

NCT: NCT06073431 · URCC-22063 · NCI-2023-04268 · URCC-22063 · URCC-22063 · URCC-22063 · UG1CA189961

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗