This study has been transitioned to CTIS with ID 2024-510812-64-00 check the CTIS register for the current data. The purpose of this study is to investigate the efficacy and safety of the investigational drug known as Lutetium (177Lu) edotreotide in…
ID
Source
Brief title
Condition
- Endocrine neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objective
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]).
Primary endpoint
Progression-free survival (PFS), defined as the time from randomization until
adequately documented Response Evaluation Criteria in Solid Tumors (RECIST)
v1.1 disease progression (based on blinded, central assessment) or death,
whichever occurs first.
Secondary outcome
Secondary objectives
1. To further demonstrate the efficacy of PRRT with lutetium (177Lu)
edotreotide.
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. To assess the safety and tolerability of PRRT with lutetium (177Lu)
edotreotide in trial patients compared to control treatment options.
Secondary endpoints
1. Further demonstration of efficacy:
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.
1.1 Objective response rate (ORR), defined as the proportion of randomized
patients with complete response (CR) or partial response (PR) (RECIST v1.1).
1.2 Overall survival (OS), defined as the time from randomization until death.
1.3 Duration of response (DoR), defined as the time from experiencing first CR
or PR until the next progressive disease (PD) (RECIST v1.1).
1.4 Disease control rate (DCR), defined as the proportion of randomized
patients with CR, PR or stable disease (SD) (RECIST v1.1).
1.5 Duration of disease control (DDC), defined as the time from experiencing
CR, PR or SD until the next subsequent PD (RECIST v1.1).
2. 2 HRQL (European Organization for Research and Treatment of Cancer [EORTC]
quality of life questionnaire [QLQ]-C30 and - GI.NET21)):
2.1 Maximum HRQL improvement in total scores relative to baseline.
2.2 Duration of maximum HRQL improvement, defined as the time from maximum
improvement until subsequent deterioration.
2.3 Time to HRQL deterioration, defined as the time from randomization until
first HRQL deterioration.
3. Safety and tolerability based on adverse events, laboratory data and vital
signs.
Background summary
Lutetium (177Lu) edotreotide is a type of therapy known as Peptide Receptor
Radionuclide Therapy (or PRRT for short). This type of therapy is described in
more detail in a later section of this document. Briefly, lutetium (177Lu)
edotreotide binds to a receptor on the surface of GEP NETs called the
*somatostatin receptor*. The cells of most GEP-NETs have an overload of these
receptors. The participant will need to have somatostatin receptor-positive
disease in order to be able to take part in the study, confirmed at entry into
the study as explained later in this document.
In this study, the effect of lutetium (177Lu) edotreotide (known as the
*Investigational Medicinal Product* or *IMP* arm) will be compared with other
drugs (known as the *control* arm) being used to treat well-differentiated G2
and G3 GEP-NETs. Several other drugs are used worldwide for this type of
cancer, but in this study, treatment will be limited to one of three options
which are considered to be the best standard of care in the regions the study
is being run. These other treatments are described in a later section of this
document. No matter which group the participant is assigned to, the quality of
your medical care will be absolutely the same. If the participant is assigned
to receive one of the other treatments, and if the disease worsens on that
treatment, it might be decide to offer the PRRT therapy outside of this study,
if this is to be considered appropriate and beneficial.
This study is being done for research purposes to collect information on how
effective and safe lutetium (177Lu) edotreotide is in patients with GEP-NETs,
specifically those classified as well differentiated Grade 2 (G2: Ki-67 between
15 and 20, both inclusive) and Grade 3 (G3: Ki-67 above 20 up to 55,
inclusive). Ki-67 is a protein that is found in growing, dividing cells but is
absent in cells not growing. Cancer cells grow and divide rapidly and Ki-67 is
considered a good marker of cell growth allowing your doctor to follow the
progress of your cancer. In this study only patients with a Ki-67 of 15 to 55
will be included, as this indicates an aggressive type of GEPNETs with poorer
outcomes and limited other treatment options. The safety information will look
at any general changes in the participants wellbeing.
Study objective
This study has been transitioned to CTIS with ID 2024-510812-64-00 check the CTIS register for the current data.
The purpose of this study is to investigate the efficacy and safety of the
investigational drug known as Lutetium (177Lu) edotreotide in comparison with
several other drugs that are already used worldwide in the treatment of
neuroendocrine tumors.
It is the aim that lutetium (177Lu) edotreotide will slow or stop tumor
progression or even reduce tumor size, thereby increasing survival and
improving symptoms in patients with neuroendocrine tumors, specifically those
which originate in the stomach or intestines (gastroenteric) or the pancreas.
Study design
This is a prospective, randomized, controlled, open-label, multi-center,
international, Phase III clinical trial to evaluate the efficacy, safety and
patient-reported outcomes of PRRT with lutetium (177Lu) edotreotide compared to
best standard of care (investigator*s choice [from the protocol comparator
list]) in patients with unresectable or metastatic, histologically confirmed,
well-differentiated aggressive G2 (Ki-67 between 15 and 20, both inclusive) and
G3 (Ki-67 above 20 up to 55, inclusive) SSTR+ GEP NETs.
Intervention
All successfully screened patients will be randomized in a 1:1 manner to
receive:
- PRRT with lutetium (177Lu) edotreotide (7.5 ± 0.7 GBq), administered as an IV
infusion for 6 cycles or until diagnosis of disease progression (101 patients),
For a given patient, trial treatment dosing should be discontinued in case of a
persistent Dose Modifying Toxicity (DMT) or if the patient withdraws consent to
continue with treatment.
Each dosis contains a mass dose of 150 µg of edotreotide (DOTATOC).
Treatment may be delayed by up to a maximum of 4 to 16 weeks depending on the
cycle if required due to safety concerns.
The cumulative lutetium (177Lu) edotreotide dose will be up to 45 GBq, which is
estimated not to exceed, on average, a
cumulative renal absorbed radiation dose of 23 Gy, as calculated based on a
blinded analysis of the dosimetry data of the first
dose administered in the COMPETE trial
(https://clinicaltrials.gov/ct2/show/NCT03049189).
or
- In the best standard of care (control) arm, each patient will receive an
Investigator*s choice of therapy from the following list: CAPTEM
(capecitabine-temozolomide), everolimus or FOLFOX (folinic acid, fluorouracil
and oxaliplatin). The choice and treatment process will be based on individual
risk-benefit assessment, institutional protocols, the local Prescribing
Information, local regulations or the local guidelines.
Also in this arm, the treatment should be discontinued in case of progression,
persistent DMT or if the patient withdraws consent.
Study burden and risks
There are risks, discomforts, and inconveniences associated with any research
study. Side effects may be experienced from taking part in this study, although
not everybody does. Side effects are mostly reversible and not all require
treatment. It is very important that any side effects, reactions, or
discomforts experienced between visits to the hospital are mentioned to the
study doctor or nurses.
Any drug may cause an allergic reaction. These symptoms, as they may be signs
of a severe allergic reaction: sudden swelling of your lips, face, throat, or
tongue, severe rash, and/or difficulty swallowing or breathing should be
reported right away to the study doctor or nurses.
Side Effects of Lutetium (177Lu) Edotreotide
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. These side effects are relatively common but are mostly temporary.
Further possible side effects include sickness, vomiting and abdominal pain
during drug administration, fatigue, changes in appetite afterwards,
constipation, diarrhea, dizziness, restlessness, discomfort in your upper
abdomen, and tumor pain. In one study participant, lutetium (177Lu) edotreotide
administration caused a pulmonary embolism (a pulmonary embolism is a clot of
material that blocks blood from getting to the lungs).
Precaution measures are implemented to downsize the discomfort and burden as
much as possible.
Lichtenbergstrasse 1
Garching 85748
DE
Lichtenbergstrasse 1
Garching 85748
DE
Listed location countries
Age
Inclusion criteria
1. Provided written informed consent.
2. Patients aged >= 18 years (fully mature per local regulations).
3. Histologically confirmed diagnosis of unresectable or metastatic,
well-differentiated GEP-NETs, with a Ki-67 index between 15 and 55, inclusive.
4. In the Investigator*s opinion, eligible to receive treatment with at least
one of the following: CAPTEM, everolimus or FOLFOX.
5. At least 1 measurable site of disease per RECIST v1.1 using contrast
computed tomography (CT)/magnetic resonance imaging (MRI).
6. SSTR+ disease.
7. All patients need to undergo an FDG PET scan within 2 months prior to
randomization and as close as possible to the PET SRI.
8. Patients may be treatment naive (first-line received in COMPOSE trial) or
have a maximum of one prior line of systemic therapy, including SSAs
(second-line received in COMPOSE trial).
9. Karnofsky-score >= 60.
Exclusion criteria
1. Known hypersensitivity to 177Lu, edotreotide, DOTA, any of the comparators,
or any excipient or derivative (e.g. rapamycin).
2. Known hypersensitivity to lysine, arginine, or any excipient of the
nephroprotective AAS given concurrently with the lutetium (177Lu) edotreotide
infusion.
3. Prior external beam radiation therapy (EBRT) to GEP-NET lesions or liver
directed selective internal radiation therapy within 12 weeks before
randomization.
4. Prior selective internal radiation therapy.
5. Prior PRRT.
6. Received chemotherapy, mammalian target of rapamycin (mTOR) inhibitors,
vascular endothelial growth factor (VEGF) pathway inhibitors, immunotherapy,
interferon, chemo-embolization, bland embolization, cyclosporine A,
locoregional treatment (e.g. cytoreduction surgery, radiofrequency ablation
[RFA], liver directed intra-arterial intervention) or SSAs within 4 weeks prior
to randomization into the trial.
7. Any major surgery within 4 weeks prior to randomization in the trial.
8. Therapy with an investigational compound and/or medical device within 30
days or 7 half-life periods (whichever is longer) prior to randomization. Live
attenuated vaccines should not be administered during the trial treatment and
over the next 3 months after the last treatment dose.
9. Patients with known brain metastases, unless these metastases have been
treated and stabilized for at least 24 weeks prior to randomization. Patients
with brain metastases must have a head CT or MRI with contrast to document
stable brain disease.
10. Other known malignancies, (except non-invasive skin cancer, superficial
bladder cancer and carcinoma of the cervix in situ), unless definitively
treated and proven no evidence of recurrence for 3 years.
11. Serious non-malignant disease (e.g. psychiatric, infectious, autoimmune,
metabolic or dementia), that may interfere with the objectives of the trial or
with the safety or compliance of the patient, as judged by the Investigator.
12. Renal, hepatic, cardiovascular, or hematological organ dysfunction,
potentially interfering with the safety of the trial treatments.
13. Current spontaneous urinary incontinence preventing safe administration of
the IMP, in the investigator's opinion.
14. Pregnancy and breast-feeding
15. Patients not able to declare meaningful informed consent on their own or
any other vulnerable population to that sense.
Design
Recruitment
Medical products/devices used
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 | CTIS2024-510812-64-00 |
| EudraCT | EUCTR2021-001086-20-NL |
| CCMO | NL77964.029.21 |