A prospective, randomised, Controlled, Open-label, Multicentre phase III study 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, somato- statin receptor-positive (SSTR+), neuroendocrine tumours of gastroenteric or pancreatic origin (GEP-NET).

Phase 1

• Conditions: patients with inoperable, progressive, somatostatin receptor-positive (SSTR+), neuroendocrine tumours of gastroenteric or pancreatic origin (GEP-NET); MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-001897-13-IT
• Lead Sponsor: ITM SOLUCIN GMBH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-07
• Last Update Posted: 7 September 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

All patients must meet all of the following criteria:
1.DWritten informed consent
2.DMale or female = 18 years of age
3.DHistologically and clinically 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), tumour grade G1 or G2 (Ki-67 < 20%), unresectable or metastatic
4.DAvailability of existing biopsy specimen from primary tumour or metastasis or, if unavailable, willingness to undergo current biopsy for secondary central analysis
5.DMeasurable disease per RECIST 1.1, on CT/MRI scans, defined as at least 1 lesion with = 1 cm in longest diameter, and = 2 radiological tumour lesions in total. A maximum of 5 target lesions visible on CT/MRI will be defined, thereof not more than 2 lesions per organ
6.DSomatostatin receptor positive (SSTR+) disease, as evidenced by
SSTR imaging (SRI) within 4 months prior to randomisation, by:
•D68Ga-based SSTR PET imaging (e.g. using 68Ga-edotreotide or 68Ga- DOTATATE), or
•D111In-pentetreotide SSTR SPECT/planar imaging, or
•D99mTc-octreotide SSTR SPECT/planar imaging
All target lesions and = 90% of non-target lesions need to be positive for SSTR, demonstrated by adequate tracer uptake, being defined as being clearly differentiable from background
7.DRadiological disease progression, defined as:
•DProgressive disease per RECIST 1.1. criteria, evidenced by consecutive morphological imaging (CT or MRI) with = 90 days interval during the 12 months prior to randomisation
8.DKarnofsky performance status (KPS) scale = 70
9.DLife expectancy of at least 6 months
10.DGlomerular filtration rate (GFR, MDRD) = 60 mL/min/1.73 m^2

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

1.Known hypersensitivity to edotreotide or everolimus
2.Known hypersensitivity to DOTA, lutetium-177, or any excipient of edotreotide or everolimus or any other Rapamycin derivative
3.Known hypersensitivity to lysine, arginine, or any excipient of the nephroprotective amino acid solution
4.Prior exposure to any peptide receptor radionuclide therapy (PRRT),
5.Prior therapy with mTor inhibitors
6.Prior EFR (extended field radiation) to GEP-NET lesions or radioembolisation therapy (e.g. 90Y microspheres,
131I-lipiodol) with administration to the liver
7.Therapy with an investigational compound and/or medical device within 30 days or 5 half-life periods (whichever is longer) prior to randomisation
8.Subjects who have received a live vaccine up to 4 weeks prior to first dose
9.Current therapy with any prohibited medication (see 6.1.1)
10.Ongoing toxicity grade 2 according to CTCAE version 4.03 from previous standard or investigational therapies
11.Indication for surgical lesion removal with curative potential
12.Planned (for the period of study participation): chemotherapy, immunotherapy, radiation therapy, chemo-embolisation, bland embolisation, radio-embolisation, treatment with cyclosporine-A
13.Neuroendocrine tumours, not meeting the inclusion criteria:
•With known non-GEP-NET origin (e.g. pulmonary or gonadal primaries)
•Functional GE-NET
•NET with unknown primaries (CUP), manifesting as liver metastases
•Poorly differentiated neuroendocrine carcinomas(G3)
•NET for which no histological specimen for secondary histological analysis can be obtained
14.Total hepatic tumour burden > 70%
15.Brain metastases
16.Secondary malignoma within previous 5 years (except basalioma)
17.Serious non-malignant disease (e.g. psychiatric, infectious, autoimmune or metabolic), that may interfere with the objectives of the study or with the safety or compliance of the subject, as judged by the investigator
18.Renal, hepatic, cardiovascular, or haematological organ dysfunction, potentially interfering with the safety of the study treatments, as follows:
•Renal
oSerum potassium > 5.0 mmol/L
oRenal obstruction
oKnown nephropathy from any cause
•Hepatic
oTotal bilirubin > 1.5 x ULN
oAST or ALT > 2.5 x ULN oDAlkaline phosphatase > 5 x ULN
oAlbumin < 3 g/dL, unless prothrombin time is within normal range oKnown cirrhosis or other distinctly restricted liver function
•Cardiovascular
oNew York Heart Association classification III & IV
oUncontrolled hypertension
•Haematopoietic oPlatelets = 80 * 10^9/L
o Absolute neutrophil count (ANC) < 1 x 10^9 cells/L
19.Pregnant or breast-feeding women. Female patients of childbearing potential or male patients with female partners of childbearing potential, unless willing to practice full and true sexual abstinence or being surgically/permanently sterile or with a history of hysterectomy for women, not willing to practice effective contraception by using: a non- oral, injected or implanted non-oestrogen progesterone based hormonal method, male condom, vaginal diaphragm, cervical cap, intrauterine device, during the study period and for 56 days after treatment in the everolimus group and 66 days in the PRRT group (10 half-lives of 177Lu) after the last treatment cycle.
20.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.).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified