Fatigue and Molecular Mechanisms in Cancer Patients Receiving CCRT

An Evaluation of Changes in the Relationships Between Fatigue and Molecular Mechanisms in Cancer Patients Receiving Curative-Intent Combined Chemotherapy and Radiation Therapy (CCRT)

Cancer-related fatigue (CRF) is a significant problem for cancer patients. This prospective, basic science, observational study will evaluate for changes in CRF associated with molecular characteristics prior to, during, and at the completion of non-investigational, standard-of-care, combined chemotherapy and radiation therapy (CCRT) and to develop and assess predictive models for CRF severity.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Head and Neck Cancer; Gynecologic Cancer; Thoracic Cancer; Gastrointestinal Cancer
• Intervention / Treatment: Procedure: Blood Specimen Collection; Other: Stool Specimen Collection; Other: Quality of Life (QOL) Questionnaires

Detailed Description

Primary Objective For mean, morning and evening CRF:

Aim 1. Evaluate for associations between phenotypic characteristics and initial levels and the trajectories of CRF.

Aim 2. Evaluate for associations between changes in CRF severity and changes in gene expression levels prior to the initiation and at the end of CCRT.

Aim 3. Evaluate for associations between changes in CRF severity and changes in circulating free cytokine levels prior to the initiation and at the end of CCRT.

Aim 4. Develop and assess predictive models for CRF severity midway, at the end of, and at least six months post-CCRT using demographic, clinical, and molecular characteristics collected prior the initiation of CCRT.

Secondary Objectives For the commonly co-occurring symptom of chemotherapy-induced peripheral neuropathy (CIPN):

Secondary Aim 5. Evaluate for associations between phenotypic characteristics and initial levels and the trajectories of CIPN.

Secondary Aim 6. Evaluate for associations between changes in CIPN severity and changes in gene expression levels prior to the initiation and at the end of CCRT.

Secondary Aim 7. Evaluate for associations between changes in CIPN severity and changes in circulating free cytokine levels prior to the initiation and at the end of CCRT.

Secondary Aim 8. Develop and assess predictive models for CIPN severity midway, at the end of, and at least six months post-CCRT using demographic, clinical, and molecular characteristics collected prior the initiation of CCRT.

Exploratory Aim 1 - Evaluate the feasibility of the protocol for the collection of stool samples.

Exploratory Aim 2 - Evaluate the feasibility of processing and storing stool samples.

Exploratory Aim 3 - Evaluate the feasibility of processing and storing performing blood samples and performing Cytometry by time of flight (CyTOF) assays.

• Study Type: Observational
• Enrollment (Estimated): 125

Contacts and Locations

• Study Contact: Name: Jamese Johnson; Phone Number: (415) 530-9805; Email: jamese.johnson@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Contact: Phone Number: 877-827-3222; Email: cancertrials@ucsf.edu
      • Principal Investigator: Sue Yom, MD
      • Contact: Jamese Johnson; Phone Number: 415-530-9805; Email: jamese.johnson@ucsf.edu
      • Principal Investigator: Kord M Kober, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult cancer patients willing to travel to San Francisco, receiving CCRT at University of California, San Francisco (UCSF) for cancers of the head and neck, gynecological, gastrointestinal, or thoracic sites.

Description

Inclusion Criteria:

• Participants have not received any prior treatment (i.e., cancer systemic therapies or radiation therapy) in the month except surgery or inductive Chemotherapy (CTX).
• Participants receiving >= 15 fractions.
• Participants is male or female and is >18 years of age on the day of signing the informed consent.
• Ability to understand a written informed consent document.
• Able and willing to complete all of the study questionnaires and provide blood and stool samples prior to, midway, and following the completion of treatment.
• Willing to have medical records reviewed for clinical information.
• Able to read, write and understand English or Spanish.

Exclusion Criteria:

• Contraindication to phlebotomy for removal of approximately 50 mL of peripheral blood within 6 week period (Institutional Review Board (IRB) limit).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Cancer Patients; Participants will have blood and stool samples collected within 5 days of any pre or post treatment timepoint prior to, during, at completion of therapy and up to 34 weeks following non-investigational, standard of care, CCRT. Participants will also be given quality of life questionnaires to complete throughout the course of the study.

Procedure: Blood Specimen Collection; Blood samples will be obtained throughout the course of the study; Other Names: Blood Specimen; Other: Stool Specimen Collection; Stool samples will be obtained throughout the course of the study; Other Names: Stool Specimen; Other: Quality of Life (QOL) Questionnaires; Surveys will be given throughout the course of the study.; Other Names: Quality of Life Surveys

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure associations between changes in cancer-related fatigue (CRF) and changes in gene expression over time	Association between phenotypic characteristics and initial levels and trajectories of CRF severity will be assessed using a hierarchical linear model (HLM) approach.	Up to 34 weeks
Measure associations between changes in CRF and changes in cytokine levels over time	Association between changes in CRF severity and biomarker levels prior to the initiation and at the end of CCRT. Linear regression will be used to evaluate for associations between fatigue changes and biomarker levels at baseline controlling for covariates identified in the initial primary outcome. Adjustments for multiple comparisons will be conducted using the Benjamini-Hochberg (BH) procedure at a false discovery rate (FDR) of 10%.	Up to 34 weeks
Measure associations between changes in CRF and changes in gene expression over time	Association between changes in CRF severity and gene expression prior to the initiation and at the end of CCRT. Linear regression will be used to evaluate for associations between fatigue changes and biomarker levels at baseline controlling for covariates identified in the initial primary outcome. Adjustments for multiple comparisons will be conducted using the Benjamini-Hochberg (BH) procedure at a false discovery rate (FDR) of 10%.	Up to 34 weeks
Evaluate the predictive utility of gene expression and cytokine data	A validated prediction model of CRF severity will be generated using machine learning (ML) methods to minimize the error between predicted and observed levels of fatigue midway through CCRT, at the completion of CCRT, and at least six months following the completion of CCRT. Evaluation of common ML algorithms for prediction accuracy and evaluation of model performance as compared to simple linear regression. Separate training and testing sets will be created, cross-validated, and repeated and impact of each variable will be determined.	Up to 34 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate for associations between changes in chemotherapy-induced peripheral neuropathy (CIPN) and changes in gene expression	The association between phenotypic characteristics and initial levels and trajectories of CIPN severity will be evaluated using a hierarchical linear model (HLM) approach.	Up to 34 weeks
Evaluate for associations between changes in CIPN and changes in cytokine levels	The association between phenotypic characteristics and initial levels and trajectories of CIPN severity will be evaluated using a hierarchical linear model (HLM) approach.	Up to 34 weeks
Evaluate the predictive utility of gene expression and severity of CIPN	The association between changes in CIPN severity and gene expression prior to the initiation and at the end of CCRT. Linear regression will be used to evaluate for associations between CIPN changes and gene expression at baseline controlling for covariates identified in previous objectives/endpoints. Adjustments for multiple comparisons will be performed using the Benjamini-Hochberg (BH) procedure at a false discovery rate (FDR) of 10%.	Up to 34 weeks
Evaluate the predictive utility of cytokine levels and severity of CIPN	The association between changes in CIPN severity and cytokine levels prior to the initiation and at the end of CCRT. Linear regression will be used to evaluate for associations between CIPN changes and cytokine levels at baseline controlling for covariates identified in previous objectives/endpoints. Adjustments for multiple comparisons will be performed using the Benjamini-Hochberg (BH) procedure at a false discovery rate (FDR) of 10%.	Up to 34 weeks
Evaluate the predictive model of severity of CIPN	The predictive utility will be assessed through a validated prediction model of CIPN severity using machine learning (ML) methods to minimize the error between predicted and observed levels of CIPN midway through CCRT, at the completion of CCRT, and at least six months following the completion of CCRT. We will evaluate common ML algorithms for prediction accuracy and evaluate their performance as compared to simple linear regression	Up to 34 weeks

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Sue Yom, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: October 7, 2024
• First Submitted That Met QC Criteria: October 7, 2024
• First Posted (Actual): October 9, 2024

Study Record Updates

• Last Update Posted (Estimated): September 16, 2025
• Last Update Submitted That Met QC Criteria: September 9, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Basic Science Research
• Additional Relevant MeSH Terms: Neoplasms by Site; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplasms; Gastrointestinal Neoplasms; Head and Neck Neoplasms; Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Therapeutics; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Data Collection; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Health Status; Demography; Epidemiologic Measurements; Surveys and Questionnaires; Phlebotomy; Quality of Life; Blood Specimen Collection
• Other Study ID Numbers: 239814; R37CA233774 (U.S. NIH Grant/Contract); NCI-2024-08455 (Registry Identifier: NCI Clinical Trials Reporting Program (CTRP))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No