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

December 6, 2024 updated by: Tine Gregersen, MD

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Tine N Gregersen, MD, PhD
  • Phone Number: +4522334161
  • Email: tigreg@rm.dk

Study Locations

  • Denmark
    • Palle Juul-Jensens Boulevard
      • Aarhus, Palle Juul-Jensens Boulevard, Denmark, 8200
        • Recruiting
        • Aarhus University Hospital, department of Nuclear medicine and PET centre
        • Contact:
          • Tine N Gregersen, MD, PhD
          • Phone Number: 004522334161
          • Email: tigreg@rm.dk
        • 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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
12 months after LPLV

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Through out the study efter each patient has completed treatment, up to 48 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Kidney toxicity
Time Frame: At baseline and after 3, 6 and 12 months
Measured by Tc-DTPA clearance
At baseline and after 3, 6 and 12 months
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
At baseline and 3 months after the last treatment
Bone marrow function, hemoglobin
Time Frame: Every second week in up to 64 weeks
Measured by hemoglobin in the two groups
Every second week in up to 64 weeks
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
Every second week in up to 64 weeks
Bone marrow function, platelets
Time Frame: Every second week in up to 64 weeks
Measured by platelets in the two groups
Every second week in up to 64 weeks
Subjective side effects
Time Frame: After every treatment, up to 48 weeks
Evaluated by use of dedicated questionaire with score from 0-3
After every treatment, up to 48 weeks
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
After every treatment, up to 48 weeks
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
After every treatment, up to 48 weeks
Overall survival
Time Frame: 3 years after LPLV
Registration of time for baseline to death
3 years after LPLV

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tine Gregersen, MD

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2020

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 1, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 7, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 8, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 9, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 6, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • EudraCT 2019-002450-23

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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