Neuroendocrine Tumors
Conditions
Keywords
non-functional and functional P-NET, non-functional GE-NET
Brief summary
The purpose of the study is to evaluate efficacy and safety of Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-Edotreotide compared to targeted molecular therapy with Everolimus in patients with inoperable, progressive, somatostatin receptor-positive (SSTR+), neuroendocrine tumours of gastroenteric or pancreatic origin (GEP-NET).
Interventions
DRUG177Lu-edotreotide PRRT
PRRT using 177Lu-edotreotide will be performed 3-monthly. A maximum of four cycles will be administered.
DRUGEverolimus
Everolimus will be administered as a standard dosis of 10 mg daily which may be reduced where required for acceptable tolerability.
OTHERAmino-Acid Solution
The Amino-Acid Solution (AAS) to be used in this study will contain a mixture of 25 g lysine and 25 g arginine diluted in 2000 mL of electrolyte solution, infused over 4 - 6 h, starting 30 - 60 min before PRRT
Sponsors
ITM Solucin GmbH
ABX CRO
PSI CRO
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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) * Measurable disease per RECIST 1.1 * Somatostatin receptor positive (SSTR+) disease * 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
* Known hypersensitivity to edotreotide or everolimus * Known hypersensitivity to DOTA, lutetium-177, or any excipient of edotreotide or everolimus or any other Rapamycin derivative * Prior exposure to any peptide receptor radionuclide therapy (PRRT) * Prior therapy with mTor inhibitors * Prior EFR (external field radiation) to GEP-NET lesions within 90 days before randomisation or radioembolisation therapy * Therapy with an investigational compound and/or medical device within 30 days prior to randomisation * Indication for surgical lesion removal with curative potential * Planned alternative therapy (for the period of study participation) * Serious non-malignant disease * Clinically relevant renal, hepatic, cardiovascular, or haematological organ dysfunction, potentially interfering with the safety of the study treatments * Pregnant or breast-feeding women * 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.).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From date of randomization until the date of first documented progression or death, assessed up to 30 months, | PFS determined as time elapsed between randomization, and the date of first objective report of tumor progression (evaluated by RECIST criteria v1.1) as evaluated by the Blinded Independent Central Review (BICR), or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 30 months | ORR will be assessed, defined as the proportion of participants achieving partial response (PR) or complete response (CR) as best outcome, after treatment with 177Lu-edotreotide compared to everolimus. |
| Overall Survival (OS) | Overall Survival (OS) will be followed up for 5 years (60 months) after the End of Study (EOS) | From the date of randomisation until the date of death up to the up to the end of the 5 year post-study follow-up. |
Countries
Australia, Austria, Belgium, Czechia, France, Germany, Italy, Netherlands, Poland, South Africa, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted in 14 countries. Of the 52 sites that screened at least one participant, 49 sites randomized at least one participant. A total of 324 participants were enrolled in the study. Of these, 309 (95.4%) were randomized in a 2:1 fashion to the 177Lu-edotreotide arm or the control arm. Of the 309 randomized participants, 7 did not receive treatment.
Pre-assignment details
The COMPETE protocol included Sub-Study C, to evaluate PK urine analysis and bone marrow dosimetry for 177Lu-edotreotide. Sub-Study C enrolled participants from the 177Lu-edotreotide arm of the COMPETE study and a non-randomized cohort. All participants in Sub-Study C received 177Lu-edotreotide.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62.8 Years STANDARD_DEVIATION 11.6 |
| BMI (Body Mass Index) | 25.32 Kg/m2 STANDARD_DEVIATION 4.5 |
| Height | 170.80 cm STANDARD_DEVIATION 9.8 |
| Race/Ethnicity, Customized Black or African American | 8 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 9 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 282 Participants |
| Race/Ethnicity, Customized Not Reported | 39 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 4 Participants |
| Race/Ethnicity, Customized White | 84 Participants |
| Sex: Female, Male Female | 44 Participants |
| Sex: Female, Male Male | 168 Participants |
| Weight | 73.84 Kg STANDARD_DEVIATION 15.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 14 / 217 | 7 / 99 |
| other Total, other adverse events | 204 / 217 | 98 / 99 |
| serious Total, serious adverse events | 66 / 217 | 44 / 99 |
Outcome results
None listed