Neoplasms

Symptoms and General Pathology

All Conditions

Rare Diseases

Neoplasm Metastasis

Neuroendocrine Tumors

Lymphatic Metastasis

Neoplastic Processes

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Edotreotide

Dihydroxyphenylalanine

Evaluation of preoperative abdominal imaging in patients who underwent an a resection for neuroendocrine tumors

evaluation of preoperative imaging (versus nodes observed on pathology)

preoperative imaging

laurent Brunaud, MD, PhD

laurent brunaud

Laurent Brunaud

Digestive NETs are the second most common malignant digestive tumor after adenocarcinoma. The most common gastrointestinal NETs arise from the small intestine. These tumors have a high lymph node and distant metastatic potential (hepatic, pulmonary, etc.). Their management is essentially surgical and the extent of the resection essentially depends on preoperative data from conventional and isotopic imaging.

The goal of surgical resection is to remove the portion of the small intestine carrying the tumour(s) with healthy margins (so-called R0 resection) and affected lymph nodes in the mesentery (lymph node dissection). The extent of lymph node dissection, sometimes significant, exposes you to the risk of short hail with its own complications (malnutrition, diarrhoea, etc.). Consequently, an analysis of the benefits and risks between the interest of an extensive and oncological resection (R0) and the risks of short bowel must be carried out for each patient.

The reference examination to define lymph node involvement is determined by the histological examination of the resected surgical specimen (reference examination). The preoperative evaluation of lymph node extension is done by preoperative abdominal CT scan. However, the preoperative CT scan is not always consistent (sensitivity and specificity) with the pathology data (reference examination). For about 5 years, isotopic imaging (DOPA-PET and DOTATOC) has become feasible and could improve the quality of preoperative evaluation of lymph node extension. Consequently, the aim of this study is to determine the contribution of isotopic imaging (DOPA-PET and DOTATOC) in the preoperative evaluation of lymph node extension.

Digestive neuroendocrine tumors (NET) are developed from neuroendocrine cells, of epithelial origin, scattered throughout the digestive tract. These tumors form a heterogeneous group defined according to the site of origin, the cell type affected, the functional character or not, the cell differentiation (morphology), and finally the potential for tumor progression and aggressiveness. Digestive NETs are the second most common malignant digestive tumor after adenocarcinoma. The most common gastrointestinal NETs arise from the small intestine. These tumors have a high lymph node and distant metastatic potential (hepatic, pulmonary, etc.). Their management is essentially surgical and the extent of the resection essentially depends on preoperative data from conventional and isotopic imaging. The goal of surgical resection is to remove the portion of the small intestine carrying the tumour(s) with healthy margins (so-called R0 resection) and affected lymph nodes in the mesentery (lymph node dissection). The extent of lymph node dissection, sometimes significant, exposes you to the risk of short hail with its own complications (malnutrition, diarrhoea, etc.). Consequently, an analysis of the benefits and risks between the interest of an extensive and oncological resection (R0) and the risks of short bowel must be carried out for each patient.

The reference examination to define lymph node involvement is determined by the histological examination of the resected surgical specimen (reference examination). The preoperative evaluation of lymph node extension is done by preoperative abdominal CT scan. However, the preoperative CT scan is not always consistent (sensitivity and specificity) with the pathology data (reference examination). For about 5 years, isotopic imaging (DOPA-PET and DOTATOC) has become feasible and could improve the quality of preoperative evaluation of lymph node extension. Consequently, the aim of this study is to determine the contribution of isotopic imaging (DOPA-PET and DOTATOC) in the preoperative evaluation of lymph node extension.

Preoperative Imaging in Patients With Small Bowel Neuroendocrine Tumors

Evaluation of Preoperative Imaging (CT Scan, DOPA-PET and DOTATOC) in Patients With Small Bowel Neuroendocrine Tumors

Evaluate the number and location of affected mesenteric lymph nodes (defined by the pathology reference) which were visualized preoperatively by conventional imaging (CT) and isotopic imaging (DOPA-TEP and DOTATOC).

Compare conventional imaging (CT) and isotopic imaging (DOPA-TEP and DOTATOC) in terms of positive predictive value of nodal involvement

Laurent BRUNAUD

Heart and Blood Diseases

Substance Related Disorders

Syndrome

Heart Diseases

Carcinoid Tumor

Malignant Carcinoid Syndrome

Serotonin Syndrome

Carcinoid Heart Disease

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Carcinoid Syndrome

Psychotropic Drugs

Antineoplastic Agents

Amino Acids

Somatostatin

Tryptophan

Lanreotide

Lanreotide 120 mg q4w Telotristat Ethyl 250 mg TID

Telotristat Ethyl

120 mg Q4W deep subcutaneous injection in the superior external quadrant of the buttock or in the upper outer thigh

Juan Valle

Angela Lamarca

This is a randomized phase III clinical trial of Lanreotide combined with Telotristat ethyl or placebo for the first-line treatment in patients with advanced well differentiated small intestinal neuroendocrine tumours (siNET) with highly-functioning carcinoid syndrome to test whether telotristat ethyl plus lanreotide is more effective than placebo plus lanreotide in reducing the number of daily bowel movements.

In addition, the study allows evaluation of the biochemical response (5-HIAA and chromogranin-A), the reduction in the number of daily cutaneous flushing episodes, the improvement in abdominal pain/discomfort, health-related quality of life, improvement in gastro-intestinal and endocrine symptoms, changes in emotional functioning, the impact of discontinuation of telotristat ethyl/placebo on HRQOL and symptoms, and the safety and toxicity of the treatment.

Patients will enter into a screening/run-in period of 1 week to establish baseline characteristics and symptomatology. The baseline assessment of daily bowel movement, as assessed in an electronic diary, will be averaged over the run-in period.

Following the screening/run-in period, patients will be randomly assigned (1:1) to either the control arm or the experimental arm for 12 months. Randomization will be stratified according to the grade of tumour differentiation (grade 1 vs. grade 2) and by baseline number of bowel movements per day (4-6 versus \>6). A total of 94 patients will be randomly assigned (1:1) to either arm.

Upon randomization, all patients will enter the 12-month treatment period with lanreotide + telotristat ethyl/placebo (blinded). In the experimental arm, patients will receive the deep subcutaneous injection of lanreotide (120 mg) every 28 days and 250 mg orally three times daily (TID) of telotristat ethyl for 12 months. In the control arm, patients will receive the deep subcutaneous injection of lanreotide every 28 days (120 mg) and placebo orally TID for 12 months.

After completion of a minimum of 6 months on randomized blinded-treatment, the protocol allows for patients on treatment with telotristat ethyl/placebo to be unblinded in the event of "lack of symptom control". Unblinding due to "lack of symptom control" can happen at any time between 6 and 12 months of the blinded-treatment period. After unblinding, patient will interrupt protocol treatment and will be further treated as per clinician discretion.

All patients will be unblinded after a maximum of 12 months on randomized blinded-treatment.

After a follow-up of 12 months, patients will go off study except patients with carcinoid heart disease. Patients off study will be further treated as per clinician discretion.

Patients with carcinoid heart disease will continue open-label treatment on study (lanreotide + telotristat ethyl or lanreotide alone according to what they were receiving at unblinding at 12 months) for 4 additional years (open-label extension period). Patients with carcinoid heart disease who discontinue protocol treatment before 12 months will also enter the extension period for additional follow-up. Additional follow-up will last 4 years for these patients and will include 6-monthly cardiological assessments.

All efficacy analyses will be conducted in the Intention-to-treat population as primary analyses i.e. all 94 randomized patients will be analyzed in the arm they were allocated by randomization. Safety analyses will be performed on the Safety population i.e. on all patients who have received at least one dose of the study drugs.

The translational research projects include blood metabolite discovery and targeted assays to find new biomarker candidates of response to Telotristat.

Human biological material that will be collected for translational research purpose:

* whole blood, plasma and serum at baseline, 4 hours after first dose, 4 weeks, 12 weeks and at end of treatment visit with telotristat/placebo (due to end of study, disease progression or lack of benefit)
* archival tissue samples (formalin-fixed paraffin-embedded) will be retrieved for all patients at study entry. In addition, one EDTA blood tube of whole blood (10 ml) at baseline, 12 weeks and end of treatment (EOT visit) might be also collected for not yet pre-defined and further translational research.

Quality of life will be assessed with the EORTC Quality of Life Questionnaire (QLQ-C30) version 3, together with the QLQ-GI.NET21 specific module designed for Neuroendocrine Tumours. The computer-adaptive testing (CAT) diarrhea scale will also be used. The baseline questionnaires must be completed during the screening period and before randomization. Subsequent questionnaires are completed at 4 weeks, 12 weeks, 24 weeks, 36 weeks and 52 weeks. Once a patient has stopped treatment, HRQoL data collection for that patient is required 1 month (28-35 days) after protocol treatment discontinuation.

Lanreotide Combined With Telotristat Ethyl or Placebo for the First-line Treatment in Patients With Advanced Well Differentiated Small Intestinal Neuroendocrine Tumours (siNET) With Highly-functioning Carcinoid Syndrome

Randomized Phase III Clinical Trial of Lanreotide Combined With Telotristat Ethyl or Placebo for the First-line Treatment in Patients With Advanced Well Differentiated Small Intestinal Neuroendocrine Tumours (siNET) With Highly-functioning Carcinoid Syndrome

The change from baseline in the number of bowel movements (BMs) per day

Intrapatient change from baseline in urine/serum/plasma 5-HIAA and chromogranin-A

Change from baseline in the number of daily cutaneous flushing episodes.

Quality of life will be assessed with the EORTC Quality of Life Questionnaire (QLQ-C30) version 3. Scale measures are: not at all; a little; quite a bit; very much.

Ipsen

European Organisation for Research and Treatment of Cancer - EORTC

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Cohorts A, B, and C: oral surufatinib 300 mg once daily in treatment cycles of 28 days starting at Cycle 1 Day1

Cohort D:

Surufatinib 300 mg once daily in treatment cycles of 28 days starting at Cycle 1 Day and single doses of drug cocktail on Day-2 and Day 15 Cycle 1

Surufatinib

John Kauh, MD

This is a Phase 2, open-label, multi-centre study of surufatinib in patients with low to intermediate grade (Grade 1 or Grade 2), well-differentiated neuroendocrine tumours (NETs).

This is a Phase 2, open-label, multi-centre study of surufatinib in patients with low- to intermediate-grade (Grade 1 or Grade 2), well-differentiated NETs.

The study will enroll 4 cohorts of varying NETs, as follows:

* Cohort A - NET of lung origin
* Cohort B - NET of small bowel origin
* Cohort C - NET of non-small bowel, non-pancreas, and non-lung origin
* Cohort D - NET of any origin (DDI substudy)

All patients will be treated with oral surufatinib 300 mg QD in treatment cycles of 28 days starting on Cycle 1 Day 1.

Open-Label Surufatinib in European Patients With NET

An Open-Label Phase 2 Study of Surufatinib in Patients With Neuroendocrine Tumours in Europe

Disease control rate the incidence of complete response, partial response and stable disease.

Blood sampling will be taken to measure levels of the study drug in all cohorts and cytochrome P450 in cohort D only

QTc change from baseline in approximately first 40 patients (Cohorts A, B, and C)

Evaluate the safety and tolerability of surufatinib in patients with NET

the duration between the enrollment date and the first disease progression (PD) or death (whichever comes first).

The duration between the date the criteria for complete response or partial response was first measured (first record shall prevail) and the date of disease recurrence or progression as objectively recorded

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Preoperative Imaging in Patients With Small Bowel Neuroendocrine Tumors	NCT05246319	Neuroendocrine ... Small Intestina... Lymph Node Meta...	preoperative im...	16 Years - 95 Years	Central Hospital, Nancy, France
Lanreotide Combined With Telotristat Ethyl or Placebo for the First-line Treatment in Patients With Advanced Well Differentiated Small Intestinal Neuroendocrine Tumours (siNET) With Highly-functioning Carcinoid Syndrome	NCT04065165	Small Intestina... Carcinoid Heart...	Telotristat Eth... Lanreotide	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
Open-Label Surufatinib in European Patients With NET	NCT04579679	Neuroendocrine ... Neuroendocrine ... Small Intestina...	Surufatinib	18 Years -	Hutchmed
Preoperative Imaging in Patients With Small Bowel Neuroendocrine Tumors	NCT05246319	Neuroendocrine ... Small Intestina... Lymph Node Meta...	preoperative im...	16 Years - 95 Years	Central Hospital, Nancy, France

Spots Global Cancer Trial Database for small intestinal net