Lutetium (177Lu) Edotreotide versus Best Standard of Care in Well-differentiated Aggressive Grade 2 and Grade 3 Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

ITM Solucin GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Sep 2021 → ongoing

Decision date (initial)

2024-07-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

ITM Solucin GmbH

External identifiers

EU CT number

2024-510812-64-00

EudraCT number

2021-001086-20

ClinicalTrials.gov

NCT04919226

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To demonstrate the efficacy of PRRT with lutetium (177Lu) edotreotide in the treatment of aggressive Grade 2 (G2; Ki67 between 15 and 20, both inclusive) and Grade 3 (G3; Ki-67 above 20 up to 55, inclusive) SSTR+ GEP-NETs compared to best standard of care (Investigator's choice [from the protocol comparator list]).

Secondary objectives 3

1. 1. To further demonstrate the efficacy of PRRT with lutetium (177Lu) edotreotide.
2. 2. To assess the impact of PRRT with lutetium (177Lu) edotreotide on trial patient's health-related quality of life (HRQL) and neuroendocrine functional tumor symptoms during and after therapy in comparison to best standard of care.
3. 3. To assess the safety and tolerability of PRRT with lutetium (177Lu) edotreotide in trial patients compared to control treatment options.

Conditions and MedDRA coding

Well-differentiated Aggressive Grade 2 and Grade 3, Somatostatin receptor-positive (SSTR+), Neuroendocrine Tumors of GastroEnteric or Pancreatic Origin (GEP-NET)

Study design 4 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003245-PIP01-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 1. Patients aged ≥18 years.
2. 2. 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).
3. 3. Somatostatin receptor-positive (SSTR+) disease.

Exclusion criteria 9

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS)

Secondary endpoints 13

1. 1. Further demonstration of efficacy:
2. 1.1 Overall survival (OS), defined as the time from randomization until death.
3. 1.2 PFS (local), defined as the time from randomization until adequately documented RECIST v1.1 disease progression (based on local assessment) or death, whichever occurs first.
4. For all endpoints based on RECIST v1.1, main analyses will be based on blinded, central assessment. Local assessments will be presented as sensitivity analyses.
5. 1.3 Disease control rate (DCR), defined as the proportion of randomized patients with complete response (CR), partial response (PR), or stable disease (SD) (RECIST v1.1).
6. 1.4 Duration of disease control (DDC), defined as the time from experiencing CR, PR or SD until the next subsequent progressive disease (PD) (RECIST v1.1).
7. 1.5 Objective response rate (ORR), defined as the proportion of randomized patients with CR or PR (RECIST v1.1).
8. 1.6 Duration of response (DoR), defined as the time from experiencing first CR or PR until PD (RECIST v1.1).
9. 2. Two HRQL (European Organization for Research and Treatment of Cancer [EORTC]) quality of life questionnaires ([QLQ]-C30 and –GI.NET21):
10. 2.1 Maximum HRQL improvement in total scores relative to baseline.
11. 2.2 Duration of maximum HRQL improvement, defined as the time from maximum improvement until subsequent deterioration.
12. 2.3 Time to HRQL deterioration, defined as the time from randomization until first HRQL deterioration.
13. 3. Safety and tolerability based on adverse events, laboratory data and vital signs.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 7

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

ITM Solucin GmbH

Sponsor organisation

ITM Solucin GmbH

Address

Lichtenbergstrasse 1

City

Garching B. Muenchen

Postcode

85748

Country

Germany

Scientific contact point

Organisation

ITM Solucin GmbH

Contact name

General Information

Public contact point

Organisation

ITM Solucin GmbH

Contact name

General Information

Third parties 13

Locations

5 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 50 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications