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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04917484
Recruitment Status : Recruiting
First Posted : June 8, 2021
Last Update Posted : June 8, 2021
Information provided by (Responsible Party):
Tine Gregersen, MD, Aarhus University Hospital

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.

Condition or disease Intervention/treatment Phase
Neuroendocrine Neoplasm Drug: Lu-177-DOTA-Octreotide Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, non blinded
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dosimetry Based PRRT Versus Standard Dose PRRT With Lu-177-DOTATOC in NEN Patients- a Randomized Study; a Step Towards Tailored PRRT
Actual Study Start Date : February 1, 2020
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2025

Arm Intervention/treatment
Active Comparator: Standard
Patients in this arm receive our standard treatment. Four treatment with standard dose of 7.4 GBq Lu-177-DOTATOC
Drug: Lu-177-DOTA-Octreotide
Lu-177-DOTATOC in standard doses or individualized doses.

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

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

Other Outcome Measures:
  1. Kidney toxicity [ Time Frame: At baseline and after 3, 6 and 12 months ]
    Measured by Tc-DTPA clearance

  2. 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

  3. Bone marrow function, hemoglobin [ Time Frame: Every second week in up to 64 weeks ]
    Measured by hemoglobin in the two groups

  4. 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

  5. Bone marrow function, platelets [ Time Frame: Every second week in up to 64 weeks ]
    Measured by platelets in the two groups

  6. Subjective side effects [ Time Frame: After every treatment, up to 48 weeks ]
    Evaluated by use of dedicated questionaire with score from 0-3

  7. 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

  8. 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

  9. Overall survival [ Time Frame: 3 years after LPLV ]
    Registration of time for baseline to death

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04917484

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Contact: Tine N Gregersen, MD, PhD +4522334161

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Aarhus University Hospital, department of Nuclear medicine and PET centre Recruiting
Aarhus, Palle Juul-Jensens Boulevard, Denmark, 8200
Contact: Tine N Gregersen, MD, PhD    004522334161   
Sub-Investigator: Anne K Arveschoug, MD         
Sub-Investigator: Peter F Staanum, Physicist, Ph.D         
Sub-Investigator: Peter Iversen, MD, PhD         
Sub-Investigator: Gitte A Dam, MD, PhD         
Sub-Investigator: Henning Gronbaek, Prof MD, PhD         
Sub-Investigator: Gerda E Villadsen, MD, PhD         
Sponsors and Collaborators
Tine Gregersen, MD
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Responsible Party: Tine Gregersen, MD, Primary investigator, Aarhus University Hospital Identifier: NCT04917484    
Other Study ID Numbers: EudraCT 2019-002450-23
First Posted: June 8, 2021    Key Record Dates
Last Update Posted: June 8, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tine Gregersen, MD, Aarhus University Hospital:
Peptide receptor radionuclide therapy
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Lutetium Lu 177 dotatate
Gastrointestinal Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action