Dosimetry Based PRRT Versus Standard Dose PRRT With Lu-177-DOTATOC in NEN Patients

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Dosimetry Based PRRT Versus Standard Dose PRRT With Lu-177-DOTATOC in NEN Patients

Study Purpose

In this study, we want to randomize patients with neuroendocrine neoplasms (NENs) who are eligible for peptide receptor radionuclide therapy (PRRT), to either standard PRRT consisting of 4 treatments with 7.4 GBq Lu-177-DOTATOC (standard arm) or 4 treatments with individualized doses of Lu-177-DOTATOC (dosimetry arm). In the dosimetry arm, the first dose depends on the patients' kidney function and thereafter the absorbed dose to the kidneys at the previous treatment. A max of 20GBq will be administered at the first treatment and 25GBq at treatment 2-4. We aim to reach an accumulated kidney dose of 24Gy. After the first treatment all patients will go through three SPECT/CT scans 24 hours, 4 days, and 7 days, after treatment to calculate absorbed kidney dose. The patients in the standard dose treatment arm will have one SPECT/CT scan after each of the last three treatments; all performed 24 hours after treatment, used to approximate the kidney dose assuming the clearance of the Lu-177 DOTATOC is the same after all treatments. The patients in the dosimetry based treatment arm will go through three SPECT/CT scans after all four treatments for dosimetry calculation. Bone marrow dosimetry is calculated after all treatments in the dosimetry based treatment arm and after the first treatment in the standard treatment arm. For bone marrow dosimetry, blood samples are drawn right before administration of Lu-177 DOTATOC (time 0) and 3 minutes, 45 minutes, 2 hours, 4 hours, 7-8 hours, 24 hours, 4 days, and 7 days after administration of Lu-177 DOTATOC. Standard blood samples are routinely drawn every 2nd week after every treatment in all included patients and analysed regarding liver, kidney and bone marrow function. Kidney clearance is evaluated with Tc-DTPA clearance at baseline. Blood and urinary samples will be collected at baseline and 3 months after the last treatment for kidney fibrosis analyses. At baseline, blood and urine samples are collected for a biobank. All included patients fill in validated quality of life questionaires at all treatments. To evaluate the effect of the treatment, all patients will be evaluated with standard CT scans prior to treatment and 3 and 9 months after the 4th treatment. Ga-68 DOTATOC PET will be performed at baseline and 6 and 12 months after the last treatment.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- 1.

Male or female patients 18 years of age or more.

- 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 more than 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: Patient glomerular filtration rate >30 ml/min 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) - 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.

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) - 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.

Known to be hypersensitive to any component of the Lu-177-DOTATOC.

- 7.

Patients with meningioma

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04917484
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Tine Gregersen, MD
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Denmark
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Neuroendocrine Neoplasm

Arms & Interventions

Arms

Active Comparator: Standard

Patients in this arm receive our standard treatment. Four treatment with standard dose of 7.4 GBq Lu-177-DOTATOC

Experimental: Dosimetry

Patients in this treatment arm receive individualized calcuted treatment depending on kidney function and kidney dose. The treatment activity can differ from one treatment to the next.

Interventions

Drug: - Lu-177-DOTA-Octreotide

Lu-177-DOTATOC in standard doses or individualized doses.

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