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

Neuroendocrine Neoplasm Clinical Trial

— DOBATOC  

Official title:

Dosimetry Based PRRT Versus Standard Dose PRRT With Lu-177-DOTATOC in NEN Patients- a Randomized Study; a Step Towards Tailored PRRT

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04917484
• Other study ID #: EudraCT 2019-002450-23
• Status: Recruiting
• Phase: Phase 2
• Start date: February 1, 2020
• Est. completion date: December 2026

Study information

• Verified date: May 2023
• Source: University of Aarhus
• Contact: Tine N Gregersen, MD, PhD
• Phone: +4522334161
• Email: tigreg[@]rm.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neuroendocrine Neoplasm
• Neuroendocrine Tumors

Intervention

Drug:
• Lu-177-DOTA-Octreotide
Lu-177-DOTATOC in standard doses or individualized doses.

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital, department of Nuclear medicine and PET centre	Aarhus	Palle Juul-Jensens Boulevard

Sponsors (1)

Lead Sponsor	Collaborator
Tine Gregersen, MD

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Kidney toxicity	Measured by Tc-DTPA clearance	At baseline and after 3, 6 and 12 months
Other	Kidney toxicity	Measured by kidney fibrosis markers PRO-C6, PRO-C3, and C3M two groups	At baseline and 3 months after the last treatment
Other	Bone marrow function, hemoglobin	Measured by hemoglobin in the two groups	Every second week in up to 64 weeks
Other	Bone marrow function, white blood cells	Measured by white blood cells in the two groups	Every second week in up to 64 weeks
Other	Bone marrow function, platelets	Measured by platelets in the two groups	Every second week in up to 64 weeks
Other	Subjective side effects	Evaluated by use of dedicated questionaire with score from 0-3	After every treatment, up to 48 weeks
Other	Quality of life score 1	Evaluated by questionnaire EORTC QLQ-30 filled out at every treatment	After every treatment, up to 48 weeks
Other	Quality of life score 2	Evaluated by questionnaire QLQ-GI.NET21. filled out at every treatment	After every treatment, up to 48 weeks
Other	Overall survival	Registration of time for baseline to death	3 years after LPLV
Primary	Progression free survival	Defined as time from randomization to documented disease progression or death by any cause, evaluated by CT, RECIST 1.1.	12 months after LPLV
Secondary	Tumor dose	Difference in tumor dose between dosimetry based and standard PRRT treatment groups and between patients in the dosimetry based treatment group over time.	Through out the study efter each patient has completed treatment, up to 48 weeks