utetium (177Lu) Edotreotide versus Best Standard of Care in Well-differentiated Aggressive Grade 2 and Grade 3 GEP-NETs
- Conditions
- Well-differentiated Aggressive Grade2 and Grade 3, Somatostatin receptor-positive (SSTR+), Neuroendocrine Tumors of GastroEnteric or Pancreatic Origin (GEP-NET)MedDRA version: 20.0Level: PTClassification code 10077559Term: Gastroenteropancreatic neuroendocrine tumour diseaseSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-001086-20-DE
- Lead Sponsor
- ITM Solucin GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 202
1. Provided written informed consent.
2. Patients aged =18 years (fully mature per local regulations).
3. Histologically confirmed diagnosis of unresectable, well-differentiated GEP-NETs, with a Ki-67 index between 15 and 55, inclusive. This should be at least confirmed by a local pathological report of a biopsy specimen of the primary tumor or metastasis, or, if unavailable, willingness to undergo current biopsy for local analysis before randomization. The biopsy should not be older than 3 years.
4. In the investigator’s opinion, patients recruited into the trial must be eligible to receive treatment with at least one of the following: CAPTEM, everolimus or FOLFOX according to individual risk-benefit assessment, institutional protocols, the latest local Prescribing Information, local regulations or the local guidelines.
5. At least 1 measurable site of disease per RECIST v1.1 using contrast computed tomography (CT)/magnetic resonance imaging (MRI). Patients who are allergic to IV contrast may be imaged without.
6. SSTR+ disease, as evidenced by locally approved 68Ga-based or 64Cu-based SSTR positron emission tomography (PET) somatostatin receptor imaging (SRI; 68Ga-DOTATOC, 68Ga-DOTATATE or 64Cu-DOTATATE) within 2 months prior to randomization and as close as possible to the fluorodeoxyglucose (FDG) PET.
a. All RECIST v1.1 selected target lesions have to be SSTR+.
b. All other lesions considered dominant by investigator must also be SSTR+ (See guidance and examples in Protocol Appendix 4).
7. All patients need to undergo a FDG PET scan within 2 months prior to randomization and as close as possible to the PET SRI.
a. FDG PET-positive RECIST v1.1 target lesions and all other FDG PET-positive lesions considered dominant by the investigator have to be SSTR+ (See guidance and examples in Protocol Appendix 4).
8. Patients may be treatment naïve (first-line) or have a maximum of one prior line of therapy, including SSAs (second-line).
a. Patients on any prior antineoplastic therapy (including SSAs) must have radiological disease progression (according to RECIST v1.1) within the 4 months prior to randomization, based on the investigator’s assessment.
b. Patients who progress on SSAs may enter the trial continuing on the same dose if required for symptom control.
9. Karnofsky performance status scale = 60.
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 135
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 67
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 amino acid solution (AAS) given concurrently with the lutetium (177Lu) edotreotide infusion
3. Prior EBRT to GEP-NET lesions or liver selective internal radiation therapy within 12 weeks before randomization
4. Prior PRRT
5. 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. Patients may be treated with SSAs for symptom control, but they must have remained on the same dose of the SSA as at the time of demonstrated disease progression.
6. Any major surgery within 4 weeks prior to randomization in the trial.
7. Therapy with an investigational compound and/or medical device within 30 days or 7 half-life periods (whichever is longer) prior to randomization.
8. Patients who have received a live attenuated vaccine up to 4 weeks 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 screening. Patients with a history of brain metastases must have a head CT or MRI with contrast to document stable brain disease prior to randomization in the study.
10. Other known malignancies, (except non-invasive skin cancer and carcinoma of the cervix in situ), unless definitively treated and proven no evidence of recurrence for 5 years.
11. Serious non-malignant disease (e.g. CNS diseases, 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, as follows:
a. Renal
i. GFR < 50 mL/min/1.73 m2 (calculated by the Chronic Kidney Disease Epidemiology [CKD-EPI] equation (Inker et al. 2021) or
ii. Creatinine clearance < 45 mL/min calculated by the Cockcroft Gault method
iii. Renal tract obstruction
b. Hepatic
i. Total bilirubin > 3 × ULN
ii. Albumin < 30 g/L, unless prothrombin time is within normal range
iii. AST/ALT > 5 × ULN
iv. Known ascites
c. Cardiovascular
i. Heart failure (New York Heart Association [NYHA] classification III and IV)
ii. Uncontrolled hypertension
d. Hyperkalemia (in accordance with local practice) if not adequately corrected before the study treatment starts
e. Hematopoietic
i. Platelets = 75 × 10e9/L
ii. ANC < 1.5 × 10e9 cells/L
iii. Hemoglobin (Hb) concentration < 5.0 mmol/L (< 8.0 g/dL)
f. Any other ongoing hematological or renal Grade 2 toxicity or other Grade 3 toxicity from previous standard or investigational therapies (NCI-CTCAE version 5.0).
13. Current spontaneous urinary incontinence preventing safe administration of the IMP, in the investigator’s opinion.
14. Pregnancy and breast-feeding:
a. Female patients of childbearing potential or male patients
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method