Survival Without Persistent Limiting Toxicity: Real Life Prospective Cohort of Advanced Neuroendocrine Tumor (TOLERATE)

March 12, 2026 updated by: Gustave Roussy, Cancer Campus, Grand Paris

Survival Without Persistent Limiting Toxicity: a Real Life Prospective Cohort of Advanced Neuroendocrine Tumor Followed in the French ENDOCAN-RENATEN and GTE Networks

Advanced neuroendocrine tumors (NETs) are rare cancers, characterized by prolonged survival (median>5 years). If five medical options are now approved and 4 others are only recommended, the best sequence is still unknown. No single study on long-term cumulative toxicity of consecutive treatment interventions has been published so far. Taking into account real-world context is required for sound decision- making that cannot be answered by randomized trials.

Project objectives and brief description of the methods, which will be used to achieve them: Study team will construct a longitudinal prospective cohort of consecutive non resectable or metastatic NET patients using the GTE-RENATEN network to evaluate the real world cumulative and limiting toxicities. They will expect, as primary endpoint, a difference in survival without limiting (>grade 1 adverse event according to nci.ctc V5) persistent (>6 months) toxicity between therapeutics classes or therapeutics sequences in the real life conditions all along the treatments lines, since metastasis diagnosis. All NET primary patients will be enrolled.

Patients will be followed until the primary endpoint is reached, death or until 5 years.

Based on our pilot study, we plan to enroll 1100 patients to detect 150 events and adjust for 15 cofounders and 10% of lost to follow-up. Cox model adapted to time-related dependency will be used to analyze the data and machine learning will be utilized to take into account the number of confounding factors, interactions and nonlinear relationship. The best model of prediction will be validated in a subgroup of the cohort population.

Expected results: Study team will create a tool to help therapeutic decision in order to identify in a given patient the best therapeutic class or sequence with the lowest risk of persistent limiting toxicity.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Tolerate is a real life longitudinal prospective cohort of NET unresectable or metastatic patients. Patients included in this study are patients followed in ENDOCAN - RENATEN expert centres which decide for each patient therapeutic sequential strategy over time according to published ESMO and national guidelines multidisciplinary local and national boards of ENDOCAN-RENATEN network.

In addition to the follow-up performed by the ENDOCAN-RENATEN centres, the TOLERATE study will propose a remote monitoring of the adverse effects caused by cancer and treatments in patients' real life by a monthly survey (TOLERATE PRO-CTC-AE) coordinated by RESILIENCE or CUREETY which are companies approved and specialized in remote monitoring in oncology.

TOLERATE study does not affect patient's care. However, patients enrolled in this study, should not be opposed (using a non-opposition letter) to answer , in addition to the monthly survey, at baseline, every 6 months and 1 month after the administration of each new treatment, up to 5 years, quality of life questionnaires (EORTC QLQ C30, GINET-21, EQ-5D-5L, preference questionnaire and pedometer)

Study Type

Observational

Enrollment (Estimated)

1100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

unresectable or metastatic NET patients

Description

Inclusion Criteria:

  • Unresectable local or metastatic NET naive of treatment tumor except somatostatin analogues or primary surgery.
  • Unresectable local or metastatic NET newly diagnosed<6 months whatever the primary NET site
  • Well differentiated neuroendocrine tumor (WHO classifications) pathologically reviewed locally
  • No initial medical absolute contraindication to any of the authorized or recommended treatments (no AE>grade 1 according to NCI CTC v.5 criteria),
  • Patient who have full medical follow-up in an expert center of the French ENDOCAN network for the management of their advanced neuroendocrine tumor
  • Patient not opposed to data collection in the on GTE databasis
  • Patient not opposed to participate in the clinical study

Exclusion Criteria:

  • Patients with severe illness that contraindicates participation to any study
  • Age <18 years old

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
TOLERATE cohort
advanced neuroendocrine cancers followed in the French ENDOCAN - RENATEN and GTE networks
Other: quality of life questionnaire, treatment side effect follow up
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What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival without persistent limiting toxicity
Time Frame: "From enrollment to the end of follow up at 5 years"
To determine the survival of unresectable or metastatic NET patients without limiting persistent toxicity (SPLT) in order to obtain decision support for the best therapeutic class or sequence depending on the patient and the treatments received
"From enrollment to the end of follow up at 5 years"

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival without persistent limiting toxicity according to nci.ctc v.5 grade 3 or 4 adverse events
Time Frame: "From enrollment to the end of follow up at 5 years"
To evaluate the survival without persistent limiting toxicity according to nci.ctc v.5 grade 3 or 4 adverse events
"From enrollment to the end of follow up at 5 years"
Survival without persistent, defined above 3 months, limiting toxicity according to nci.ctc v.5 grade >1 adverse events
Time Frame: "From enrollment to the end of follow up at 5 years"
To analyze the survival without persistent, defined above 3 months, limiting toxicity according to nci.ctc v.5 grade >1 adverse events
"From enrollment to the end of follow up at 5 years"
Best treatment line sequencing
Time Frame: "From enrollment to the end of follow up at 5 years"
Best treatment line sequencing in terms of maximizing SPLT after adjustment to comorbidity, modality of follow-up and prognostic parameters
"From enrollment to the end of follow up at 5 years"
Duration of each active treatment
Time Frame: "From enrollment to the end of follow up at 5 years"
To analyze the duration of each active treatments and therapeutic breaks
"From enrollment to the end of follow up at 5 years"
Best response according to local RECIST 1.1
Time Frame: "From enrollment to the end of follow up at 5 years"
To determine best response according to local RECIST 1.1 evaluation per line
"From enrollment to the end of follow up at 5 years"
Progression free survival
Time Frame: "From enrollment to the end of follow up at 5 years"
To determine progression free survival to local RECIST 1.1 evaluation per line
"From enrollment to the end of follow up at 5 years"
Time to next line systemic therapy
Time Frame: "From enrollment to the end of follow up at 5 years"
To determine time to next line systemic therapy per line
"From enrollment to the end of follow up at 5 years"
Overall survival
Time Frame: "From enrollment to the patient's death"
To determine overall survival (whatever death cause) from the date of diagnosis of unresectable or metastatic tumor
"From enrollment to the patient's death"
Specific survival
Time Frame: "From enrollment to the patient's death"
To determine specific survival (death related to NET progression or toxicity due to therapeutic intervention)
"From enrollment to the patient's death"

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gustave Roussy, Cancer Campus, Grand Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

June 1, 2034

Study Completion (Estimated)

June 1, 2034

Study Registration Dates

First Submitted

March 5, 2026

First Submitted That Met QC Criteria

March 12, 2026

First Posted (Actual)

March 13, 2026

Study Record Updates

Last Update Posted (Actual)

March 13, 2026

Last Update Submitted That Met QC Criteria

March 12, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-A02354-43
  • CSET number 2023/3770 (Other Identifier: Gustave Roussy)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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