Clinical trial NCT05064150: Neuroendocrine Tumors - Patient Reported Outcomes
Official title: A Cohort Study of Symptom Burden and Therapeutic Selection in Neuroendocrine Tumors (NETs)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Neuroendocrine Tumors
Gastroenteropancreatic Neuroendocrine Tumor
Lung Neuroendocrine Neoplasm
Neuroendocrine Carcinoma
Keywords: Patient-reported outcomes
Neuroendocrine
Quality of Life
Survival
Treatment sequencing
Symptom burden
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: Allina Health System
name: Medical College of Wisconsin
name: University of Kansas Medical Center
name: University of Texas Southwestern Medical Center
name: University of Utah
name: University of Florida
name: Ohio State University
name: University of Michigan
name: University of Pittsburgh Medical Center
name: Medical University of South Carolina
name: University of North Carolina, Chapel Hill
name: Vanderbilt University Medical Center
name: Mayo Clinic
name: Northern California CarciNET Community
name: Neuroendocrine Cancer Awareness Network
name: Neuroendocrine Tumor Research Foundation
name: Healing NET Foundation
name: Patient-Centered Outcomes Research Institute
First posted: 2021-10-01
Enrollment: 2539
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief 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 09/30/2024 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 (2515 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.

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.

Eligibility criteria: 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 09/30/2024, 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

Primary outcomes:
measure: European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC QLQ-C30)
timeFrame: Change in score across baseline, 6, 12, and 18 month time points.
measure: European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire - Neuroendocrine Carcinoid Module (EORTC QLQ-GI.NET21)
timeFrame: Change in score across baseline, 6, 12, and 18 month time points.
measure: Sequencing of treatment regimens from electronic medical records (% of patients using modality)
timeFrame: Up to 5 years
measure: Renal function
timeFrame: Change in score across baseline, 6, 12, and 18 month time points.
Secondary outcomes:
measure: Norfolk Carcinoid Symptom Score
timeFrame: Change in score across baseline, 6, 12, and 18 month time points.
measure: Experiences with cancer care (from CANCORS)
timeFrame: Change in score across baseline, 6, 12, and 18 month time points.
measure: Progression-free survival
timeFrame: 1-, 3-, and 5-year
measure: Overall survival
timeFrame: Up to 5 years
measure: Adverse toxicities
timeFrame: Up to 5 years
measure: Presence of Acute Renal Failure Diagnosis
timeFrame: Up to 5 years
measure: Health related Quality of Life (HRQoL) by PRRT regimen
timeFrame: Change in score across baseline, 6, 12, and 18 month time points.
measure: Symptom scores by PRRT regimen
timeFrame: Change in score across baseline, 6, 12, and 18 month time points.
measure: Renal toxicity (creatinine clearance) by PRRT isotope
timeFrame: Up to 5 years
measure: Renal toxicity of PRRT by primary tumor location & grade 3 disease
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute, Inc
state: Kansas
city: Ann Arbor
country: United States
facility: Regents of the University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Allina Health System
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: The Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, Inc
state: Wisconsin
Study officials:
affiliation: University of Iowa
name: Michael O'Rorke, PhD
role: PRINCIPAL_INVESTIGATOR
References: