E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with neuroendocrine neoplasms origin from the gastrointestinal tract, pancreas, adrenal glands (pheochromocytomas.), lungs, or from unknown primary site |
Neuroendokrine neoplasmer |
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E.1.1.1 | Medical condition in easily understood language |
Patients with neuroendocrine neoplasms origin from the gastrointestinal tract, pancreas, adrenal glands (pheochromocytomas.), lungs, or from unknown primary site |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10062476 |
E.1.2 | Term | Neuroendocrine tumor |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary: • Difference in progression free survival between NEN patients treated with dosimetry based versus standard PRRT. Defined as time from randomization to documented disease progression or death by any cause.
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E.2.2 | Secondary objectives of the trial |
Our secondary endpoints are: • Difference in tumor dose between dosimetry based and standard PRRT treatment groups • Difference in kidney toxicity between dosimetry based and standard PRRT treatment groups, measured by creatine, eGFR, cystatin-c, Tc-DTPA clearance, and kidney fibrosis markers PRO-6, C3M and LAMC1. • Difference in bone marrow function between dosimetry based and standard PRRT treatment groups, measured by hemoglobin, white blood cells, platelets. • Difference in subjective side effects between dosimetry based and standard PRRT treatment groups, evaluated by questionnaire. • Difference in quality of life between dosimetry based and standard PRRT treatment groups, evaluated by questionnaire EORTC QLQ-30 and QLQ-GI.NET21. • Difference in overall survival between dosimetry based and standard PRRT treatment groups. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients > 18 years of age 2. NEN confirmed by histology 3. Clinical, PET/CT or CT proven progression despite standard treatment with somatostatin analogues, targeted therapy (Everolimus, sunitinib), chemotherapy (STZ/5-FU, temozolomide/capecitabine) OR intolerable side effects caused by these standard treatment OR unmanageable carcinoid symptoms. 4. WHO/ ECOG Performance Status of 0-2. 5. Life expectancy > 6 months 6. Uptake higher than liver in primary tumor or metastases on Ga-DOTATOC PET/CT (Krenning 3 or 4), if the scan is more than 3 months old at inclusion time, a new scan should be done. 7. Adequate organ function as defined by: • Adequate kidney function: Standard glomerular filtration rate >30 ml/min/m2 measured by Tc-DTPA clearance • Adequate bone marrow function: • WBC ≥ 2.0 x 109/L • Platelets ≥ 100 x 109/L • Hb ≥ 6 mmol/l (≥9.67 g/dL ) • No evidence of significant liver disease: • Serum bilirubin < 40 µmol/L • Albumin > 20g/L 8. Willingness and ability to comply with scheduled visits for SPECT/CT scans, treatment plans, laboratory tests and other study procedures. 9. Written informed consent obtained prior to any screening procedures
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E.4 | Principal exclusion criteria |
1. Tumor amenable to surgery and/or radiofrequency ablation. 2. Patients who are unable to stay isolated for 24 hours 3. Previous PRRT 4. Female patients who are pregnant or lactating. Women who are of childbearing potential (defined as all women physiologically capable of becoming pregnant) have to practice an effective method of contraception/birth control. Fertile female patients have to take a urinary pregnancy test, to ensure that they are not pregnant, before they can enter the study. After entering the study, they have to use effective contraception during the study period and 6 months after. Effective contraception methods include: • Use of oral, injected or implanted hormonal methods of contraception or • Placement of an intrauterine device (IUD) or intrauterine system (IUS) • Barrier methods of contraception: condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository can be used if hormonal contraception is not tolerated. Both have to be used at the same time. • Total abstinence or patient sterilization (male or female) 5. Male patients are not allowed to conceive pregnancy for 6 months after last treatment cycle 6. Patients with meningioma
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E.5 End points |
E.5.1 | Primary end point(s) |
• Difference in progression free survival between NEN patients treated with dosimetry based versus standard PRRT. Defined as time from randomization to documented disease progression or death by any cause, evaluated by CT, RECIST 1.1. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Difference in tumor dose between dosimetry based and standard PRRT treatment groups • Difference in kidney toxicity between dosimetry based and standard PRRT treatment groups, measured by creatine, eGFR, cystatin-c, Tc-DTPA clearance, and kidney fibrosis markers PRO-6, C3M and LAMC1. • Difference in bone marrow function between dosimetry based and standard PRRT treatment groups, measured by hemoglobin, white blood cells, platelets. • Difference in subjective side effects between dosimetry based and standard PRRT treatment groups, evaluated by questionnaire. • Difference in quality of life between dosimetry based and standard PRRT treatment groups, evaluated by questionnaire EORTC QLQ-30 and QLQ-GI.NET21. • Difference in overall survival between dosimetry based and standard PRRT treatment groups.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Some can be evaluated right af LPLV and some several year after depending on how long the patients survive. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard dose vs dosimetry based dose |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study is estimated to end 5 years after FPFV. Inclusion is estimated to take 3.5 years. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |