Efficacy and Safety of 177Lu-edotreotide PRRT in GEP-NET Patients (COMPETE)

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

24 Nov 2017 → ongoing

Decision date (initial)

2024-07-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

ITM Solucin GmbH

External identifiers

EU CT number

2023-510444-21-00

EudraCT number

2016-001897-13

ClinicalTrials.gov

NCT03049189

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To demonstrate the efficacy of PRRT with 177Lu-edotreotide to prolong progression-free survival (PFS) in patients with inoperable, progressive, SSTR+ GEP-NET, compared to everolimus

Secondary objectives 2

1. 1. To assess objective response rates (ORR), defined as the proportion of patients achieving partial response (PR) or complete response (CR) as best outcome, after treatment with 177Lu-edotreotide compared to everolimus
2. 2. To assess overall survival (OS), defined as the time from the date of randomisation until death

Conditions and MedDRA coding

Neuroendocrine tumours of gastroenteric or pancreatic origin

Study design 3 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 6

1. 1. Written informed consent
2. 2. Male or female ≥18 years of age
3. 3. Histologically confirmed diagnosis of well-differentiated neuro-endocrine tumour of non-functional gastroenteric origin (GE-NET) or both functional or non-functional pancreatic origin (P-NET)
4. 4. Measurable disease per RECIST 1.1
5. 5. Somatostatin receptor positive (SSTR+) disease
6. 6. Progressive disease based on RECIST 1.1. criteria as evidenced by two morphological imaging examinations made with the same imaging method (either CT or MRI)

Exclusion criteria 12

1. 1. Known hypersensitivity to edotreotide or everolimus
2. 2. Known hypersensitivity to DOTA, lutetium-177, or any excipient of edotreotide or everolimus or any other Rapamycin derivative.
3. 3. Prior exposure to any peptide receptor radionuclide therapy (PRRT)
4. 4. Prior therapy with mTor inhibitors
5. 5. Prior EFR (external field radiation) to GEP-NET lesions within 90 days before randomisation or radioembolisation therapy.
6. 6. Therapy with an investigational compound and/or medical device within 30 days prior to randomization
7. 7. Indication for surgical lesion removal with curative potential
8. 8. Planned alternative therapy (for the period of study participation)
9. 9. Serious non-malignant disease
10. 10. Clinically relevant renal, hepatic, cardiovascular, or haematological organ dysfunction, potentially interfering with the safety of the study treatments
11. 11. Pregnant or breast-feeding women
12. 12. Subjects not able to declare meaningful informed consent on their own (e.g. with legal guardian for mental disorders) or any other vulnerable population to that sense (e.g. persons institutionalised, incarcerated etc.)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Progression-free survival (PFS)

Secondary endpoints 17

1. 1. Objective response rate (ORR), % patients achieving PR or CR as best outcome
2. 2. Overall survival (OS)
3. 3. Safety and tolerability-Measured TER, percentage depart from baseline value
4. 4. Safety and tolerability-Calculated GFR, percentage depart from baseline value
5. 5. Safety and tolerability-Renal volume (Vkidney), percentage depart from baseline value
6. 6. Safety and tolerability-Frequency of occurrence and severity of abnormal findings in safety investigations (vital signs, 12-lead ECG, clinical laboratory, adverse events)
7. 7. Health-related quality of life (HRQL)- Maximum HRQL improvement (EORTC QLQ-C30 and GI.NET21 questionnaires) total scores, relative to baseline
8. 8. Health-related quality of life (HRQL)- Duration of maximum HRQL improvement
9. 9. Health-related quality of life (HRQL)- Time to HRQL deterioration, defined as the time from randomisation to first HRQL deterioration
10. 10. Dosimetry- Full dosimetry assessments of target organs and tumour lesions
11. 11. Dosimetry- Cumulative absorbed dose (in Gy) from 177Lu-edotreotide to target tumour lesions, estimated from 177Lu-edotreotide dosimetry after first dose
12. 12. Dosimetry- Sub-study A patients: cumulative absorbed dose to kidneys and to tumour lesions extrapolated from absorbed dose estimated at D1 compared with the cumulative absorbed dose measured at the different administration times (i.e. D1 to D4)
13. 13. Dosimetry- Sub-study B patients: absorbed dose (in Gy) determined by 3D dosimetry compared to absorbed dose values obtained by planar (2D) and hybrid (2D/3D) dosimetry
14. 14. Dosimetry- Sub-study C patients: bone marrow absorbed dose (in Gy) extrapolated from blood radioactivity
15. 15. Pharmacokinetics (Sub-study C) Urine radioactivity in percentage of injected activity (%IA) at pre-defined intervals within 48 hours post-injection to assess excretion pattern
16. 16. Pharmacokinetics (Sub-study C) Blood radioactivity in %IA at pre-defined time points within 7 days post-injection to assess clearance pattern
17. 17. Pharmacokinetics (Sub-study C)_Radiochemical purity assessed through HPLC of urine samples collected within 48 hours post-injection

Investigational products

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

Test 1

Comparator 2

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

9 EU/EEA countries · 33 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 69 files

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

Application history

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