This study has been transitioned to CTIS with ID 2023-510444-21-00 check the CTIS register for the current data. The primary objective is to demonstrate the efficacy of Peptide Receptor Radionuclide Therapy with 177Lu-edotreotide to prolong…
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is progression-free survival (PFS). Diagnosis of
progression and liver tumour burden will be established based on
radiological information from morphological imaging (MRI and/or CT) according
to RECIST 1.1. Stratification will be made for primary tumour origin (GE-NET
vs. P-NET) and prior medical therapy (1st line vs. 2nd line). Tumour grade (G1,
G2), and baseline Karnofsky score will be used for further statistical subgroup
analyses.
Secondary outcome
Secondary endpoints include parameters of morphological and biomarker tumour
response such as objective response rate (ORR), overall survival
(OS), disease control rates (DCR), as well as duration of disease control
(DDC), safety, health-related quality of life (HRQL). Furthermore, exploratory
analyses will be performed on patient and tumour characteristics, as well as
the degree of 177Lu-edotreotide uptake for traits predicting PRRT efficacy.
Background summary
PRRT is a treatment option that is highly effective in controlling advanced,
progressive neuroendocrine tumours. PRRT has been shown to help relieve
symptoms and slow the progression of the disease. PRRT is an option for
patients who are not candidates for surgery and who have advanced and/or
progressive neuroendocrine tumours. Main goals of PRRT are to provide symptom
relief, to stop or slow tumour progression and to improve overall survival.
So far only one randomised prospective evaluation of PRRT has been performed
with 177Lu-DOTATATE. The NETTER-1 study only enrolled patients with midgut
neuroendocrine tumors. The academic study, conducted at the ENETS centre in
Germany showed for inoperable GEP-NETs treated with two or more cycles of
177Lu-edotreotide an unprecedented objective response rate of 54%.
In this study the efficacy and safety of PRRT with 177Lu-edotreotide in
patients with metastatic GEP-NET, in comparison to established medical therapy
is investigated, using a prospective randomised controlled trial. Everolimus
has been selected as comparator drug. Everolimus has an innovative mode of
action, high clinical acceptance, and a well-documented evidence of efficacy.
Study objective
This study has been transitioned to CTIS with ID 2023-510444-21-00 check the CTIS register for the current data.
The primary objective is to demonstrate the efficacy of Peptide Receptor
Radionuclide Therapy with 177Lu-edotreotide to prolong progression free
survival in patients with inoperable, progressive, somatostatin
receptor-positive (SSTR+), neuroendocrine tumours of gastroenteric or
pancreatic origin (GEP-NET), compared to Everolimus.
Study design
A prospective, randomised, controlled, open-label, multicentre phase III study
Study burden and risks
* Side effects associated with 177Lu-edotreotide PRRT:
Potential risks caused by 177Lu-edotreotide PRRT may arise from side effects
associated with radiation exposure and somatostatin-related side effects:
damage to (healthy) cells. One common side effect is the reduction of blood
cells that leads to an increased risk of bleeding, faster exhaustion, shortness
of breath and infections. The subject will have to discontinue from the study
in case the decrease in number of blood cells last for a long period. Further
side effects may be sickness, vomiting and abdominal pain during drug
administration, fatigue, changes in appetite afterwards, constipation, diarrhea
and dizziness.
* Side effects associated with everolimus treatment
Everolimus (Afinitor®) can cause serious side effects including lung or
breathing problems, infections and kidney failure which can lead to death.
Everolimus can cause incisions to heal slowly or not heal well. Mouth ulcers
and mouth sores are common side effects, occurring in up to 78% of patients
taking everolimus. Everolimus can affect blood cell counts, kidney and liver
function, and blood sugar and cholesterol levels.
* Side effects associated with study procedures
There are certain risks and discomforts associated with study procedures.There
can be pain, swelling, and/or bruising at the site where blood is drawn for lab
assessments, as well as possible inflammation of the vein or an infection at
this site. Mild skin rash (irritation, reddening or itching) can occur during
an ECG at places where electrodes are placed. An imaging procedure may be
uncomfotable and/or giving a claustrophobic sensation and an injection with
intravenous contrast may give itching, a rash, hives, or a feeling of warmth
throughout the body.
Lichtenbergstrasse 1
Garching D-85748
DE
Lichtenbergstrasse 1
Garching D-85748
DE
Listed location countries
Age
Inclusion criteria
1. Written informed consent
2. Male or female >=18 years of age
3. Histologically and clinically confirmed diagnosis of well-differentiated
neuroendocrine tumour of non-functional gastroenteric origin (GE-NET) or both
functional or non-functional pancreatic origin P-NET), grade G1 or G2 (Ki-67 <
20%), unresectable or metastatic, in a patient who is either treatment-naïve
(1st line) or who has progressed under prior therapy (2nd line)
Exclusion criteria
1. Known hypersensitivity to edotreotide or everolimus
2. Known hypersensitivity to DOTA, lutetium-177, or any excipient of
edotreotide or everolimus
3. Known hypersensitivity to lysin, arginin, or any excipient of the
nephroprotective amino acid solution
Design
Recruitment
Medical products/devices used
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-510444-21-00 |
| EudraCT | EUCTR2016-001897-13-NL |
| CCMO | NL60840.018.17 |