Neuroendocrine Tumors - Patient Reported Outcomes (NET-PRO)

A Cohort Study of Symptom Burden and Therapeutic Selection in Neuroendocrine Tumors (NETs)

With so many therapeutic options available (i.e.: biologic therapy, liver directed therapy, radiotherapy and chemotherapy), the purpose of this project is to partner with patients on comparative effectiveness research (CER) to achieve the goal of alleviating undue toxicity, and optimizing effectiveness and sequencing of therapy for neuroendocrine tumors (NET) patients. We will conduct a study of all newly occurring GEP-NET and lung NET cases aged 18 years and older diagnosed between 01/01/2018 through 12/31/2023 across 14 sites participating in the National Patient-Centered Clinical Research Network (PCORnet), enrolling an average of 215 patients per site over the 3 year study period (~3,000 patients total), allowing up to 60 months of follow-up for medical record outcomes. Participants will complete four online or paper surveys over 18 months; these surveys will focus on patient-reported outcomes, including questions on quality of life, treatment decisions, and experiences with cancer care. Survey data will be linked to participant medical record data to achieve study aims.

Study Overview

• Status: Enrolling by invitation
• Conditions: Neuroendocrine Tumors; Neuroendocrine Carcinoma; Lung Neuroendocrine Neoplasm; Gastroenteropancreatic Neuroendocrine Tumor

Detailed Description

NETs are a group of neoplasms that occur most frequently in the gastrointestinal tract, pancreas and the lungs, collectively referred to as gastroenteropancreatic (GEP-NETs) and lung-NETs. There are currently fewer than 180,000 patients living with this condition in the United States, meeting the criteria for rare disease status. NETs are typically slow growing, with vague signs and a myriad of symptoms (carcinoid syndrome) leading to diagnostic delays. Thus, NET patients typically experience a prolonged clinical course with active disease, and many have significant symptom burdens. However, assessment of quality of life outside of therapy trials remains scarce and of poor quality. What's more, over half of GEP-NETs are diagnosed with spread of their disease at diagnosis and are not candidates for curative surgery. Fortunately, many of these tumors are amenable to long-term medical treatment with somatostatin analogues (SSAs)- which slow down the production of hormones, especially serotonin, which helps to control the symptoms of carcinoid syndrome. However, living with distant spread of the disease increases the probability for the disease to progress. Following failure of first-line SSA therapy there are no clear consensus guidelines as to the optimum sequencing of other therapeutic options. NET patients are left wondering not only 'what therapy would be best to try next?', but 'if I were to take this option now, what treatment options will be closed off to me in the future?' and clinicians are unsure as to how best to tailor treatment selection on the characteristics of the patient and their tumor.

There is currently no large nationally recruiting prospective (forward in time) observational study of NET patients. Our large study will robustly generate real-world evidence on the frequency and sequence of commonly used treatments for GEP and lung NET patients in relation to Patient Reported Outcomes (PROs) and survival/progression, endpoints that matter most to NET patients, their caregivers, and clinicians involved in their care. Given the lack of consensus guidelines as to the optimum sequencing of treatments, evidence generated in this study will aid patient (and clinician) navigation and selection of the next most appropriate therapy, accounting for the preferences and needs of the individual patient, whilst respecting the underlying profile of their tumor. Moreover, the infrastructure this study will generate (i.e.: electronic identification of NET patients, entry and completion of tumor table data in PCORnet, and a unique NET patient health record portal), will foster future CER studies in NETs and other rare diseases.

The four specific aims of this project are:

1. To describe the frequency of treatment regimens received by line of therapy, and examine their association with symptom burden and changes in 6, 12 and 18 month health-related quality of life (HRQoL) outcomes. The influence of patient preferences, beliefs, attitudes, and experience of care on choice of these treatment regimens will also be examined.
2. To examine the association of patient, clinical, and tumor characteristics on the selection of first-line and beyond treatment regimens and compare the effects of common treatment sequences on frequency of subsequent treatments received and outcomes of overall survival and disease progression.
3. To compare the effectiveness of peptide receptor radionuclide therapy (PRRT) regimens on outcomes of renal toxicity, disease progression, and patient-reported symptoms and HRQoL.
4. To disseminate lessons learned and expand enrollment of the prospective cohort to patient advocate organizations, and to use the infrastructure developed to aid in the study of other rare diseases.

• Study Type: Observational
• Enrollment (Estimated): 3010

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32611-5500
      • University of Florida
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66103-2937
      • University of Kansas Medical Center Research Institute, Inc
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-1340
      • Regents of the University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Allina Health System
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-1350
      • The University of North Carolina at Chapel Hill
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15260-3203
      • University of Pittsburgh
  • South Carolina
    • Charleston, South Carolina, United States, 29407-4636
      • The Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390-9020
      • UT Southwestern Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Inclusion/exclusion criteria will be assessed by a combination of a computable phenotype (computer code or algorithm) that is run against participating site electronic medical record and/or tumor registry data holdings, and/or manual review of patient EMR; and patient self-report.

Description

Inclusion Criteria:

• (1) Adults age 18 years or older at time of NET diagnosis
• (2) Diagnosis of GEP-NET or lung NET between 1/1/2018 and 12/31/2023, as evidenced by
• (a) medical record information on diagnoses and/or medications and/or treatments and/or test results and/or clinical notes and/or procedures and/or encounters and/or tumor characteristics, and
• (b) patient self-attestation of their diagnosis.

Exclusion Criteria:

Any GEP-NET/Lung NET prior to 1/1/18, as evidenced by medical record information on diagnoses and/or medications and/or treatments and/or test results and/or clinical notes and/or procedures and/or encounters and/or tumor characteristics

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
NET patient observational cohort; Patients diagnosed with lung or gastrointestinal neuroendocrine tumors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC QLQ-C30)	Incorporates five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea and vomiting), a global health status / QoL scale, and a number of single items assessing additional symptoms commonly reported by cancer patients (dyspnea, loss of appetite, insomnia, constipation and diarrhea) and perceived financial impact of the disease. Responses to the QLQ-C30 will be linearly transformed to a 0-100 scale using EORTC guidelines, a higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms.	Change in score across baseline, 6, 12, and 18 month time points.
European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire - Neuroendocrine Carcinoid Module (EORTC QLQ-GI.NET21)	The QLQ-GINET21 contains a total of 21 items: four single-item assessments relating to muscle and/or bone pain (MBP), body image (BI), information (INF) and sexual functioning (SX), together with 17 items organized into five proposed scales: endocrine symptoms (ED; three items), GI symptoms (GI; five items), treatment-related symptoms (TR; three items), social functioning (SF) of the new module (SF21; three items) and disease-related worries (DRW; three items). Responses to the QLQ-GINET21 will be linearly transformed to a 0-100 scale using EORTC guidelines, with higher scores reflecting more severe symptoms.	Change in score across baseline, 6, 12, and 18 month time points.
Sequencing of treatment regimens from electronic medical records (% of patients using modality)	Ordering of treatment receipt i.e.: first-line, 2nd line 3rd line therapies	Up to 5 years
Renal function	Creatinine clearance loss (per/Yr)	Change in score across baseline, 6, 12, and 18 month time points.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Norfolk Carcinoid Symptom Score	Patient-reported symptoms	Change in score across baseline, 6, 12, and 18 month time points.
Experiences with cancer care (from CANCORS)	13 items to assess cancer care as described at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953972/	Change in score across baseline, 6, 12, and 18 month time points.
Progression-free survival	Time to event	1-, 3-, and 5-year
Overall survival	Time to event	Up to 5 years
Adverse toxicities	Incident acute renal failure, dialysis and liver failure during follow-up	Up to 5 years
Presence of Acute Renal Failure Diagnosis	Common Data Model (CDM) diagnosis codes for acute renal failure and dialysis	Up to 5 years
Health related Quality of Life (HRQoL) by PRRT regimen	Changes in HRQOL	Change in score across baseline, 6, 12, and 18 month time points.
Symptom scores by PRRT regimen	Changes in symptom scores	Change in score across baseline, 6, 12, and 18 month time points.
Renal toxicity (creatinine clearance) by PRRT isotope	Creatinine clearance loss (per/Yr) 177Lu vs 90Y	Up to 5 years
Renal toxicity of PRRT by primary tumor location & grade 3 disease	Creatinine clearance loss (per/Yr) GEP-NETs vs lung NETs and G3	Up to 5 years

Collaborators and Investigators

• Sponsor: University of Iowa
• Collaborators: Patient-Centered Outcomes Research Institute; Medical University of South Carolina; Mayo Clinic; University of Michigan; University of Florida; Medical College of Wisconsin; Vanderbilt University Medical Center; Ohio State University; University of Kansas Medical Center; University of North Carolina, Chapel Hill; University of Texas Southwestern Medical Center; University of Utah; University of Pittsburgh Medical Center; Allina Health System; Northern California CarciNET Community; Neuroendocrine Cancer Awareness Network; Neuroendocrine Tumor Research Foundation; Healing NET Foundation
• Investigators: Principal Investigator: Michael O'Rorke, PhD, University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2022
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: August 27, 2021
• First Submitted That Met QC Criteria: September 21, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 7, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Survival; Quality of Life; Patient-reported outcomes; Neuroendocrine; Symptom burden; Treatment sequencing
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasms; Carcinoma, Neuroendocrine; Neuroendocrine Tumors
• Other Study ID Numbers: 202104599

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) will be made available to researchers and details will be provided.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

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