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

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ClinicalTrials.gov Identifier: NCT04917484
Recruitment Status : Recruiting
First Posted : June 8, 2021
Last Update Posted : June 8, 2021
Sponsor:
Information provided by (Responsible Party):
Tine Gregersen, MD, Aarhus University Hospital

Tracking Information
First Submitted Date  ICMJE September 1, 2020
First Posted Date  ICMJE June 8, 2021
Last Update Posted Date June 8, 2021
Actual Study Start Date  ICMJE February 1, 2020
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 7, 2021)
Progression free survival [ Time Frame: 12 months after LPLV ]
Defined as time from randomization to documented disease progression or death by any cause, evaluated by CT, RECIST 1.1.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2021)
Tumor dose [ Time Frame: Through out the study efter each patient has completed treatment, up to 48 weeks ]
Difference in tumor dose between dosimetry based and standard PRRT treatment groups and between patients in the dosimetry based treatment group over time.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 7, 2021)
  • Kidney toxicity [ Time Frame: At baseline and after 3, 6 and 12 months ]
    Measured by Tc-DTPA clearance
  • Kidney toxicity [ Time Frame: At baseline and 3 months after the last treatment ]
    Measured by kidney fibrosis markers PRO-C6, PRO-C3, and C3M two groups
  • Bone marrow function, hemoglobin [ Time Frame: Every second week in up to 64 weeks ]
    Measured by hemoglobin in the two groups
  • Bone marrow function, white blood cells [ Time Frame: Every second week in up to 64 weeks ]
    Measured by white blood cells in the two groups
  • Bone marrow function, platelets [ Time Frame: Every second week in up to 64 weeks ]
    Measured by platelets in the two groups
  • Subjective side effects [ Time Frame: After every treatment, up to 48 weeks ]
    Evaluated by use of dedicated questionaire with score from 0-3
  • Quality of life score 1 [ Time Frame: After every treatment, up to 48 weeks ]
    Evaluated by questionnaire EORTC QLQ-30 filled out at every treatment
  • Quality of life score 2 [ Time Frame: After every treatment, up to 48 weeks ]
    Evaluated by questionnaire QLQ-GI.NET21. filled out at every treatment
  • Overall survival [ Time Frame: 3 years after LPLV ]
    Registration of time for baseline to death
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Dosimetry Based PRRT Versus Standard Dose PRRT With Lu-177-DOTATOC in NEN Patients
Official Title  ICMJE Dosimetry Based PRRT Versus Standard Dose PRRT With Lu-177-DOTATOC in NEN Patients- a Randomized Study; a Step Towards Tailored PRRT
Brief 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomized, non blinded
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neuroendocrine Neoplasm
Intervention  ICMJE Drug: Lu-177-DOTA-Octreotide
Lu-177-DOTATOC in standard doses or individualized doses.
Study Arms  ICMJE
  • Active Comparator: Standard
    Patients in this arm receive our standard treatment. Four treatment with standard dose of 7.4 GBq Lu-177-DOTATOC
    Intervention: Drug: Lu-177-DOTA-Octreotide
  • 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.
    Intervention: Drug: Lu-177-DOTA-Octreotide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 7, 2021)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2025
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Tine N Gregersen, MD, PhD +4522334161 tigreg@rm.dk
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04917484
Other Study ID Numbers  ICMJE EudraCT 2019-002450-23
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Tine Gregersen, MD, Aarhus University Hospital
Study Sponsor  ICMJE Tine Gregersen, MD
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University of Aarhus
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP