An Observational Research Study to Uncover Subtypes of Cancer Cachexia, LOTUS-CC Study (LOTUS-CC)

• ClinicalTrials.gov Identifier: NCT06073431
• Recruitment Status: Recruiting
• First Posted: October 10, 2023
• Last Update Posted: April 25, 2024
• Sponsor: University of Rochester NCORP Research Base
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Richard Dunne, University of Rochester NCORP Research Base

Tracking Information

• First Submitted Date: October 3, 2023
• First Posted Date: October 10, 2023
• Last Update Posted Date: April 25, 2024
• Actual Study Start Date: December 4, 2023
• Estimated Primary Completion Date: January 1, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 3, 2023)

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 ]

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. First, will examine the distributions of each variable and assess the need for using transformations to achieve normality for continuous variables (log transformation, quartiles, or clinically important thresholds), collapsing similar variables into single categories, and excluding g conditions that are too rare (< 1% of the cohort). Next, will assess statistical correlations using the Jaccard similarity metric for binary variables and the Pearson correlation for continuous variables to determine highly correlated variables that may provide redundant information.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Observational Research Study to Uncover Subtypes of Cancer Cachexia, LOTUS-CC Study
• Official Title: Longitudinal Observational Trial to Uncover Subtypes of Cancer Cachexia
• Brief Summary: 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). 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 tumors 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 actigraphy over 24 hours for 7 days to record daily sleep and exercise activity at baseline and 3-month follow-up. Patients' medical records are also reviewed at baseline, 3-month and 1-year follow-up.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Blood and tissue

• Sampling Method: Non-Probability Sample
• Study Population: Patients undergoing treatment for non-small cell lung cancer (NSCLC), pancreatic adenocarcinoma, colorectal cancer.
• Condition: Cancer Cachexia (CC)
• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 3, 2023): 800
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 1, 2028
• Estimated Primary Completion Date: January 1, 2028 (Final data collection date for primary outcome measure)

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 receive 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Ashley Mack, MS; 585-275-1090; URCC_22063@urmc.rochester.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT06073431
• Other Study ID Numbers: URCC-22063; OT2CA278664 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Currently, there is no plan to make individual participant data (IPD) available to other researchers.

• Current Responsible Party: Richard Dunne, University of Rochester NCORP Research Base
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Rochester NCORP Research Base
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Study Chair: Richard Dunne, MD, MS; University of Rochester NCORP Research Base

• PRS Account: University of Rochester
• Verification Date: April 2024