Neuroendocrine Tumors - Patient Reported Outcomes

Neuroendocrine Tumors Clinical Trial

— NET-PRO  

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05064150
• Other study ID #: 202104599
• Status: Enrolling by invitation
• Start date: May 10, 2022
• Est. completion date: June 2026

Study information

• Verified date: June 2024
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 3010
• Est. completion date: June 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Neuroendocrine
• Gastroenteropancreatic Neuroendocrine Tumor
• Lung Neuroendocrine Neoplasm
• Neoplasms
• Neuroendocrine Carcinoma
• Neuroendocrine Tumors

Locations

Country	Name	City	State
United States	Regents of the University of Michigan	Ann Arbor	Michigan
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	The Medical University of South Carolina	Charleston	South Carolina
United States	The Ohio State University	Columbus	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	University of Florida	Gainesville	Florida
United States	University of Iowa	Iowa City	Iowa
United States	University of Kansas Medical Center Research Institute, Inc	Kansas City	Kansas
United States	Medical College of Wisconsin, Inc	Milwaukee	Wisconsin
United States	Allina Health System	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	University of Utah	Salt Lake City	Utah

Sponsors (19)

Lead Sponsor

Collaborator

University of Iowa

Allina Health System, Healing NET Foundation, Mayo Clinic, Medical College of Wisconsin, Medical University of South Carolina, Neuroendocrine Cancer Awareness Network, Neuroendocrine Tumor Research Foundation, Northern California CarciNET Community, Ohio State University, Patient-Centered Outcomes Research Institute, University of Florida, University of Kansas Medical Center, University of Michigan, University of North Carolina, Chapel Hill, University of Pittsburgh Medical Center, University of Texas Southwestern Medical Center, University of Utah, Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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
Primary	Renal function	Creatinine clearance loss (per/Yr)	Change in score across baseline, 6, 12, and 18 month time points.
Secondary	Norfolk Carcinoid Symptom Score	Patient-reported symptoms	Change in score across baseline, 6, 12, and 18 month time points.
Secondary	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.
Secondary	Progression-free survival	Time to event	1-, 3-, and 5-year
Secondary	Overall survival	Time to event	Up to 5 years
Secondary	Adverse toxicities	Incident acute renal failure, dialysis and liver failure during follow-up	Up to 5 years
Secondary	Presence of Acute Renal Failure Diagnosis	Common Data Model (CDM) diagnosis codes for acute renal failure and dialysis	Up to 5 years
Secondary	Health related Quality of Life (HRQoL) by PRRT regimen	Changes in HRQOL	Change in score across baseline, 6, 12, and 18 month time points.
Secondary	Symptom scores by PRRT regimen	Changes in symptom scores	Change in score across baseline, 6, 12, and 18 month time points.
Secondary	Renal toxicity (creatinine clearance) by PRRT isotope	Creatinine clearance loss (per/Yr) 177Lu vs 90Y	Up to 5 years
Secondary	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