Neuroendocrine NeoplasmPhase 2DOBATOCNCT04917484
Dosimetry Based PRRT Versus Standard Dose PRRT With Lu-177-DOTATOC in NEN Patients
A Phase 2 study testing Lu-177-DOTA-Octreotide in people with Neuroendocrine Neoplasm, run by Tine Gregersen, MD at 1 site in Denmark.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuroendocrine Neoplasm
- What is being tested?
- Lu-177-DOTA-Octreotide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Feb 2020to Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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)
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- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site, 1 recruiting
- Recruiting
Aarhus University Hospital, department of Nuclear medicine and PET centre
Aarhus, Palle Juul-Jensens Boulevard, 8200
Tine N Gregersen, MD, PhD, 004522334161, tigreg@rm.dk
Anne K Arveschoug, MD
About this study
Official title: 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.
Read more
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.
- Conditions
- Neuroendocrine Neoplasm
- Being tested
- Lu-177-DOTA-Octreotide
- Keywords
- Peptide receptor radionuclide therapy, Dosimetry
- Medical subject headings
- Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lu-177-DOTA-OctreotideDrug
Lu-177-DOTATOC in standard doses or individualized doses.
| Study group | Role | What they receive |
|---|---|---|
| Standard | Active comparator | Patients in this arm receive our standard treatment. Four treatment with standard dose of 7.4 GBq Lu-177-DOTATOC Receives: Drug: Lu-177-DOTA-Octreotide |
| Dosimetry | Experimental | 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. Receives: Drug: Lu-177-DOTA-Octreotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
Defined as time from randomization to documented disease progression or death by any cause, evaluated by CT, RECIST 1.1.
Measured: 12 months after LPLV
Secondary outcomes (1)
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.
Measured: Through out the study efter each patient has completed treatment, up to 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2021
- Study start1 Feb 2020
- Primary completionDec 2025 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neuroendocrine NeoplasmStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, non blinded
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tine Gregersen, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Tine Gregersen, MD, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04917484
- Sponsor's protocol ID
- EudraCT 2019-002450-23
- Acronym
- DOBATOC
- Status last verified
- Dec 2024
- First submitted
- 1 Sep 2020
- Last updated
- 9 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Di Franco M, Zanoni L, Fortunati E, Fanti S, Ambrosini V. Radionuclide Theranostics in Neuroendocrine Neoplasms: An Update. Curr Oncol Rep. 2024 May;26(5):538-550. doi: 10.1007/s11912-024-01526-5. Epub 2024 Apr 6.
PubMed 38581469
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dosimetry Based PRRT Versus Standard Dose PRRT With Lu-177-DOTATOC in NEN Patients- a Randomized Study; a Step Towards Tailored PRRT
- ClinicalTrials.gov ID
- NCT04917484
- Acronym / sponsor ID
- DOBATOC / EudraCT 2019-002450-23
- Conditions
- Neuroendocrine Neoplasm
- Keywords
- Peptide receptor radionuclide therapy, Dosimetry
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Tine Gregersen, MDUniversity, hospital or other
- Study start
- 1 Feb 2020 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 8 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized, non blinded
| Arm | Type | Receives |
|---|---|---|
| Standard | Active comparator | Drug: Lu-177-DOTA-OctreotidePatients in this arm receive our standard treatment. Four treatment with standard dose of 7.4 GBq Lu-177-DOTATOC |
| Dosimetry | Experimental | Drug: Lu-177-DOTA-OctreotidePatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lu-177-DOTA-OctreotideLu-177-DOTATOC in standard doses or individualized doses. | Drug | Dosimetry, Standard |
Primary outcome
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.
1 secondary outcome
Tumor dose
Time frame: Through out the study efter each patient has completed treatment, up to 48 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2024.
- Derived from this study: PubMed 38581469Di Franco M, Zanoni L, Fortunati E, Fanti S, Ambrosini V. Radionuclide Theranostics in Neuroendocrine Neoplasms: An Update. Curr Oncol Rep. 2024 May;26(5):538-550. doi: 10.1007/s11912-024-01526-5. Epub 2024 Apr 6.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lu-177-DOTA-Octreotide in people with Neuroendocrine Neoplasm, run by Tine Gregersen, MD at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tine N Gregersen, MD, PhD (+4522334161, tigreg@rm.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: 12 months after LPLV). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04917484, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2024.