Lutetium 177Lu-Edotreotide Versus Best Standard of Care in Well-differentiated Aggressive Grade-2 and Grade-3 GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs) - COMPOSE

Sponsor

ITM Solucin GmbH (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04919226

Collaborator

(none)

202

Enrollment

Locations

Arms

56.3

Anticipated Duration (Months)

11.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the efficacy, safety & patient-reported outcomes of peptide receptor radionuclide therapy (PRRT) with 177Lu-Edotreotide as 1st or 2nd line of treatment compared to best standard of care in patients with well-differentiated aggressive grade 2 and grade 3, somatostatin receptor-positive (SSTR+), neuroendocrine tumours of gastroenteric or pancreatic origin.

Condition or Disease	Intervention/Treatment	Phase
Neuroendocrine Tumors	Drug: 177Lu-Edotreotide (Peptide Receptor Radionuclide Therapy) PRRT Drug: CAPTEM (Capecitabine and Temozolomide) Other: Amino-Acid Solution Drug: Everolimus Drug: FOLFOX (Folinic acid + Fluorouracil + Oxaliplatin)	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

202 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Prospective, Randomised, Controlled, Open-label, Multicentre Study to Evaluate Efficacy, Safety and Patient-Reported Outcomes of Peptide Receptor Radionuclide Therapy (PRRT) With 177Lu-Edotreotide Compared to Best Standard of Care in Patients With Well-differentiated Aggressive Grade 2 and Grade 3, Somatostatin Receptor-Positive (SSTR+), Neuroendocrine Tumours of GastroEnteric or Pancreatic Origin

Actual Study Start Date :

Dec 21, 2021

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Sep 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Peptide Receptor Radionuclide Therapy (PRRT) Arm	Drug: 177Lu-Edotreotide (Peptide Receptor Radionuclide Therapy) PRRT Peptide Receptor Radionuclide Therapy (PRRT) using 177Lu-edotreotide with a defined number of cycles will be administered. Other Names: 177Lu-DOTATOC 177Lu-Edo Other: Amino-Acid Solution The Amino-Acid Solution (AAS) to be used in this study will contain a mixture of lysine and arginine diluted in an electrolyte solution. Other Names: Arginine-Lysine Solution
Active Comparator: CAPTEM(Capecitabine-Temozolomide), Everolimus, FOLFOX(Folinic acid + Fluorouracil + Oxaliplatin)	Drug: CAPTEM (Capecitabine and Temozolomide) Best standard of care treatment (investigator's choice [from the protocol comparator list]) according to individual risk-benefit assessment, institutional protocols, the local Prescribing Information, local regulations, or the local guidelines. Drug: Everolimus Best standard of care treatment (investigator's choice [from the protocol comparator list]) according to individual risk-benefit assessment, institutional protocols, the local Prescribing Information, local regulations, or the local guidelines. Drug: FOLFOX (Folinic acid + Fluorouracil + Oxaliplatin) Best standard of care treatment (investigator's choice [from the protocol comparator list]) according to individual risk-benefit assessment, institutional protocols, the local Prescribing Information, local regulations, or the local guidelines.

Arm

Intervention/Treatment

Experimental: Peptide Receptor Radionuclide Therapy (PRRT) Arm

Drug: 177Lu-Edotreotide (Peptide Receptor Radionuclide Therapy) PRRT

Peptide Receptor Radionuclide Therapy (PRRT) using 177Lu-edotreotide with a defined number of cycles will be administered.

Other Names:

177Lu-DOTATOC 177Lu-Edo

Other: Amino-Acid Solution

The Amino-Acid Solution (AAS) to be used in this study will contain a mixture of lysine and arginine diluted in an electrolyte solution.

Other Names:

Arginine-Lysine Solution

Active Comparator: CAPTEM(Capecitabine-Temozolomide), Everolimus, FOLFOX(Folinic acid + Fluorouracil + Oxaliplatin)

Drug: CAPTEM (Capecitabine and Temozolomide)

Best standard of care treatment (investigator's choice [from the protocol comparator list]) according to individual risk-benefit assessment, institutional protocols, the local Prescribing Information, local regulations, or the local guidelines.

Drug: Everolimus

Drug: FOLFOX (Folinic acid + Fluorouracil + Oxaliplatin)

Outcome Measures

Primary Outcome Measures

Progression-Free Survival [Every 12 weeks from randomization until disease progression or death whichever occurs earlier, during the time necessary to observe 148 Progression Free Survival (PFS) events.]
PFS (Progression-Free Survival), defined as the time from randomization until documented RECIST v1.1 (Response evaluation criteria in solid tumors) progression.

Secondary Outcome Measures

Overall Survival [Up to 2 years after disease progression]
OS (Overall Survival), defined as the time from randomization until death;

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients aged ≥ 18 years.
Histologically confirmed diagnosis of unresectable, well-differentiated GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs). measurable site of disease per RECIST v1.1 (Response evaluation criteria in solid tumors) using contrast computed tomography (CT) / magnetic resonance imaging (MRI).
Somatostatin receptor-positive (SSTR+) disease.

Exclusion Criteria:

Known hypersensitivity to Lutetium 177Lu, edotreotide, DOTA (dodecane tetraacetic acid), any of the comparators, or any excipient or derivative (e.g. rapamycin).
Prior (Peptide Receptor Radionuclide Therapy) PRRT.
Any major surgery within 4 weeks prior to randomization in the trial.
Therapy with an investigational compound and/or medical device within 30 days or 7 half-life periods (whichever is longer) prior to randomization.
Other known malignancies.
Serious non-malignant disease.
Renal, hepatic, cardiovascular, or hematological organ dysfunction, potentially interfering with the safety of the trial treatments.
Pregnant or breastfeeding women.
Patients not able to declare meaningful informed consent on their own or any other vulnerable population to that.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University Alvin J. Siteman Cancer Center	Saint Louis	Missouri	United States	63110
2	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
3	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
4	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia	VIC 3000
5	Haut-Leveque Hospital, Department of Hepatogastroenterology and Digestive Tract Oncology	Pessac	Bordeaux	France	33604
6	Nantes University Hospital Center - Hotel Dieu Hospital	Nantes	Cedex	France	44093
7	Edouard Herriot Hospital, Medical Oncology Unit	Lyon		France	69003
8	IUCT Oncopole - Institut Universitaire du Cancer de Toulouse	Toulouse		France	31059
9	All India Institute Of Medical Sciences, Nuclear Medicine	New Delhi	Delhi	India	110029
10	HCG Cancer Centre, Medical Oncology	Bangalore	Karnataka	India	560027
11	VU Medical Center (VUMC), Department of Medical Oncology	Amsterdam		Netherlands	1081-HV
12	University Hospital Vall d'Hebron, Department of Medical Oncology	Barcelona		Spain	08035
13	ICO Hospitalet, Catalan Institute of Oncology	Barcelona		Spain	199-203
14	University Hospital 12 de Octubre, Department of Gastroenterology	Madrid		Spain	28041
15	Central University Hospital de Asturias (HUCA), IUOPA - Universitary Institute of Oncology	Oviedo		Spain	33011
16	University Hospital Complex of Santiago (CHUS)	Santiago De Compostela		Spain	15706
17	University and Polytechnic Hospital La Fe, Endocrinology	Valencia		Spain	46026
18	Uppsala University Hospital, Department of Oncology	Uppsala		Sweden	75185