Neuroendocrine TumorsPhase 2LUFORNCT06045260
"Receptor Radionuclide Therapy With 177Lu-DOTATOC
A Phase 2 study testing 177Lu-DOTATOC in people with Neuroendocrine Tumors and Paraganglioma, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 2 sites in Italy.
Trial summary
Peptide receptor radionuclide therapy (PRRT) may be recommended in G1- G2 GEP-NET patients with disease progression on somatostatine analogues therapy (LUTATHERA®). However, there are several diseases, including neuroendocrine neoplasia not originating from the digestive tract, for which the efficacy of PRRT has… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuroendocrine Tumors, Paraganglioma, Pheochromocytoma
- What is being tested?
- 177Lu-DOTATOC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 2 sitesItaly
- Study dates
- 13 Sep 2023to Jan 2027
- 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
- Age ≥18 years.
- Patients must have histologically or cytologically confirmation of neuroendocrine tumors or any other tumor histology type documented as sst2-positive, that may benefit from receptor radionuclide therapy and for which there are not any other effective treatments, included locoregional methods of control for PPGLs/pheochromocytoma. For cerebral and PPGLs sst2- positive tumors, if biopsy is no feasible for technical reason or risk benefit balance, patients may be enrolled if CT or MRI strongly suggest oncological lesion confirming the 68Ga PET-CT dota-peptide SSTr2 positivity.
- Measurable disease according to RECIST 1.1 criteria also patients without measurable but with evaluable disease can be enrolled.
- Any disease stage is allowed. Patients with documented disease will be admitted to the therapeutic phase only if the diagnostic PET/CT 68Ga-peptide images demonstrate a significant uptake in the tumour, according to the adapted Krenning Scale. Only patients with a greater caption (Grade 3 or 4) in most of the lesions will be admitted.
- Patients with progressive disease in pre-study period (PD within the last 12 months), refractory to conventional standard treatments; clinical progression is allowed.
- Patients with or without concurrent therapy with somatostatin analogs. It will be maintained the same dose of the SSA analogs as at the time of demonstrated disease progression.
Show all 11Show fewer
- Life expectancy of greater than 6 months.
- ECOG performance status <2.
- Adequate haematological, liver and renal function: haemoglobin >= 9 g/dL, absolute neutrophil count (ANC) >= 1.5 x 109 /L, platelets >= 100 x 109 /L, bilirubin ≤1.5 X UNL (upper normal limit), ALT and AST <2.5 X UNL (< 5 X UNL in presence of liver metastases), creatinine < 2 mg/dL and/or eGFR or creatinine clearance > 50 ml/min.
- If female of childbearing potential highly effective birth control methods, according to guideline "Recommendation related to contraception and pregnancy testing in clinical trials", (2014_09_15 section 4.1) are mandatory (see Appendix F). Highly effective birth control methods are required beginning at the screening visit and continuing until 6 months following last treatment with study drug. A negative serum pregnancy test should be performed the same day the treatment is started at any cycle. Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 6 months after final study drug administration. Two acceptable methods of birth control thus include Condom (barrier method of contraception) and one of the following is required (established use of oral, or injected or implanted hormonal method of contraception by the female partner; placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner; additional barrier method like occlusive cap with spermicidal foam/gel/film/cream/suppository in the female partner; tubal ligation in the female partner; vasectomy or other procedure resulting in infertility (eg, bilateral orchiectomy), for more than 6 months (see Appendix F).
- Participant is willing and able to give informed consent for participation in the study.
Who cannot join
- Patients treated with chemotherapy and therapeutic radiotherapy within 4 weeks and treated within 2 weeks with palliative radiotherapy, hormonal or biological therapy.
- Known hypersensitivity to lutetium-177 (177Lu), edotreotide, DOTA or components of the formulation or other radiolabeled peptide agents.
- Known hypersensitivity to lysine, arginine, or any excipient of the nephroprotective aminoacids given concurrently with the lutetium (177Lu) edotreotide infusion;
- Patients treated with prior external beam radiation therapy (EBRT) to more than 25% of the bone marrow.
- Patients treated with previous PRRT with an absorbed dose to the kidney more than 23 Gy and more than 1.8 Gy for the bone marrow or as surrogate of dosimetry (13).
- Patients which are included in the indication of LUTATHERA®(9).
Show all 11Show fewer
- All acute toxic effects of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to a grade ≤ 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE).
- ECOG performance status >2.
- Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or breastfeeding women are excluded from the present study.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Italy2 sites, 2 recruiting
- Not yet recruiting
AUSL Romagna - Ospedale "M. Bufalini"
Cesena, Forlì-Cesena, 47521
Federica Matteucci, 0543739339, federica.matteucci@irst.emr.it
- Recruiting
IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l.
Meldola, Forlì-Cesena, 47014
Maddalena Sansovini, 0543739100, maddalena.sansovini@ist.emr.it
About this study
Official title: "Receptor Radionuclide Therapy With 177Lu-DOTATOC (177Lu-edotreotide or 177Lu-octreotide) in SSTR Positive Patients: a Multicenter, Prospective, Phase II Trial"
Peptide receptor radionuclide therapy (PRRT) may be recommended in G1- G2 GEP-NET patients with disease progression on somatostatine analogues therapy (LUTATHERA®). However, there are several diseases, including neuroendocrine neoplasia not originating from the digestive tract, for which the efficacy of PRRT has already been demonstrated, but which are not currently within the indications of LUTATHERA and therefore cannot benefit from it (i.e. bronchopulmonary, ovarian, renal NETs and neuroendocrine carcinomas). Moreover, the role of PRRT is also accepted in Pheochromocytomas and paragangliomas (PPGLs), Meningiomas, but also as a salvage therapy in pre-treated NET pts, and other SSTR-positive malignancies (Lymphomas, Gliomas…). Least explored among radiopharmaceuticals for SSTR-positive tumors is 177Lu-DOTATOC. This study aims to investigate the efficacy and safety of lutetium (177Lu) edotreotide (Lu-Dotatoc) on all the above-mentioned diseases that could benefit from receptor radionuclide therapy. We believe that this study, which will involve only patients outside the indication of LUTATHERA, will expand the current knowledge of radionuclide receptor therapy with 177Lu- DOTATOC, particularly with regard to objective response and safety parameters, and may consolidate its in the management of these diseases.
- Conditions
- Neuroendocrine Tumors, Paraganglioma, Pheochromocytoma
- Being tested
- 177Lu-DOTATOC
- Medical subject headings
- Neuroendocrine Tumors, Paraganglioma, Pheochromocytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
177Lu-DOTATOCDrug
Administration of 4 cycles of therapy with 7.4 Gbq Dose for No risk factors Arm and 5.5 Gbq Dose for Risk Factor Arm. Both through slow intravenous infusion in 30 minutes with a dedicated pump system.
| Study group | Role | What they receive |
|---|---|---|
| 7.4 Gbq Dose | Experimental | Patients with less than 2 risk factors out of the following will receive a dose equal to 7.4 GBq of the experimental radiopharmaceutical 177Lutetium-DOTATOC:
* Pre-existing renal impairment (Creatinine > 1.5 mg/dl and/or eGFR or creatinine clearance >50 and < 60 ml/min) or(chemotherapy, local external radiotherapy);
* Patients who have received earlier nephrotoxic treatment modalities (chemotherapy, local external field radiation);
* Relevant renal morphological abnormalities;
* Previously major (G3-4) iatrogenic toxicities;
* ECOG = 2;
* Any previous Peptide Receptor Radionuclide Therapy;
* Type 1 or 2 diabetes not controlled with therapy;
* Arterial hypertension not controlled with therapy;
* Extension of disease = 4 according to "tumor burden Krenning scale" (9);
* Age (>80 years). Receives: Drug: 177Lu-DOTATOC |
| 5.5 Gbq Dose | Experimental | Patients with al least 2 risk factors out of the following will receive a dose equal to 5.5 GBq of the experimental radiopharmaceutical 177Lutetium-DOTATOC:
* Pre-existing renal impairment (Creatinine > 1.5 mg/dl and/or eGFR or creatinine clearance >50 and < 60 ml/min) or(chemotherapy, local external radiotherapy);
* Patients who have received earlier nephrotoxic treatment modalities (chemotherapy, local external field radiation);
* Relevant renal morphological abnormalities;
* Previously major (G3-4) iatrogenic toxicities;
* ECOG = 2;
* Any previous Peptide Receptor Radionuclide Therapy;
* Type 1 or 2 diabetes not controlled with therapy;
* Arterial hypertension not controlled with therapy;
* Extension of disease = 4 according to "tumor burden Krenning scale" (9);
* Age (>80 years). Receives: Drug: 177Lu-DOTATOC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy as Disease control rate (DCR)
percentage of patients who have achieved complete response, partial response, stable disease (according to RECIST 1.1) at the 1st planned evaluation.
Measured: 32 months
Secondary outcomes (4)
(Safety) percentage of patients who experience acute toxicity
evaluated according to version 5.0 CTC-AE (Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE). Safety is defined as the percentage of patients who experience acute toxicity from the 1st treatment until 30 days after the last treatment cycle or late toxicity that occurred after 30 days from the last treatment administration up to 6 months.
Measured: 37 months
Progression free survival
Time from the start treatment date to the date of first observation of documented disease progression or death due to any cause.
Measured: 44 months
Overall survival
Time from the therapy start to the date of death due to any cause or the date of last contact (censored observation) at the date of data cut-off.
Measured: 44 months
Quality of life
Evaluated through validated standardized data collection forms from the EORTC QLQ-C30 questionnaire.
Measured: 32 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2023
- Study start13 Sep 2023
- Primary completionFeb 2025 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuroendocrine TumorsStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Maddalena Sansovini, Study chair, IRCCS IRSTFederica Matteucci, Principal investigator, IRCCS IRST
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06045260
- Sponsor's protocol ID
- IRST 100.60
- Acronym
- LUFOR
- Status last verified
- Aug 2024
- First submitted
- 13 Sep 2023
- Last updated
- 13 Aug 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "Receptor Radionuclide Therapy With 177Lu-DOTATOC (177Lu-edotreotide or 177Lu-octreotide) in SSTR Positive Patients: a Multicenter, Prospective, Phase II Trial"
- ClinicalTrials.gov ID
- NCT06045260
- Acronym / sponsor ID
- LUFOR / IRST 100.60
- Conditions
- Neuroendocrine Tumors, Paraganglioma, Pheochromocytoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCSUniversity, hospital or other
- Study start
- 13 Sep 2023 (actual)
- Primary completion
- Feb 2025 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 21 Sep 2023 (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.
Peptide receptor radionuclide therapy (PRRT) may be recommended in G1- G2 GEP-NET patients with disease progression on somatostatine analogues therapy (LUTATHERA®). However, there are several diseases, including neuroendocrine neoplasia not originating from the digestive tract, for which the efficacy of PRRT has already been demonstrated, but which are not currently within the indications of LUTATHERA and therefore cannot benefit from it (i.e. bronchopulmonary, ovarian, renal NETs and neuroendocrine carcinomas). Moreover, the role of PRRT is also accepted in Pheochromocytomas and paragangliomas (PPGLs), Meningiomas, but also as a salvage therapy in pre-treated NET pts, and other SSTR-positive malignancies (Lymphomas, Gliomas…). Least explored among radiopharmaceuticals for SSTR-positive tumors is 177Lu-DOTATOC. This study aims to investigate the efficacy and safety of lutetium (177Lu) edotreotide (Lu-Dotatoc) on all the above-mentioned diseases that could benefit from receptor radionuclide therapy. We believe that this study, which will involve only patients outside the indication of LUTATHERA, will expand the current knowledge of radionuclide receptor therapy with 177Lu- DOTATOC, particularly with regard to objective response and safety parameters, and may consolidate its in the management of these diseases.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 7.4 Gbq Dose | Experimental | Drug: 177Lu-DOTATOCPatients with less than 2 risk factors out of the following will receive a dose equal to 7.4 GBq of the experimental radiopharmaceutical 177Lutetium-DOTATOC: * Pre-existing renal impairment (Creatinine > 1.5 mg/dl and/or eGFR or creatinine clearance >50 and < 60 ml/min) or(chemotherapy, local external radiotherapy); * Patients who have received earlier nephrotoxic treatment modalities (chemotherapy, local external field radiation); * Relevant renal morphological abnormalities; * Previously major (G3-4) iatrogenic toxicities; * ECOG = 2; * Any previous Peptide Receptor Radionuclide Therapy; * Type 1 or 2 diabetes not controlled with therapy; * Arterial hypertension not controlled with therapy; * Extension of disease = 4 according to "tumor burden Krenning scale" (9); * Age (>80 years). |
| 5.5 Gbq Dose | Experimental | Drug: 177Lu-DOTATOCPatients with al least 2 risk factors out of the following will receive a dose equal to 5.5 GBq of the experimental radiopharmaceutical 177Lutetium-DOTATOC: * Pre-existing renal impairment (Creatinine > 1.5 mg/dl and/or eGFR or creatinine clearance >50 and < 60 ml/min) or(chemotherapy, local external radiotherapy); * Patients who have received earlier nephrotoxic treatment modalities (chemotherapy, local external field radiation); * Relevant renal morphological abnormalities; * Previously major (G3-4) iatrogenic toxicities; * ECOG = 2; * Any previous Peptide Receptor Radionuclide Therapy; * Type 1 or 2 diabetes not controlled with therapy; * Arterial hypertension not controlled with therapy; * Extension of disease = 4 according to "tumor burden Krenning scale" (9); * Age (>80 years). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age ≥18 years.
- Patients must have histologically or cytologically confirmation of neuroendocrine tumors or any other tumor histology type documented as sst2-positive, that may benefit from receptor radionuclide therapy and for which there are not any other effective treatments, included locoregional methods of control for PPGLs/pheochromocytoma. For cerebral and PPGLs sst2- positive tumors, if biopsy is no feasible for technical reason or risk benefit balance, patients may be enrolled if CT or MRI strongly suggest oncological lesion confirming the 68Ga PET-CT dota-peptide SSTr2 positivity.
- Measurable disease according to RECIST 1.1 criteria also patients without measurable but with evaluable disease can be enrolled.
- Any disease stage is allowed. Patients with documented disease will be admitted to the therapeutic phase only if the diagnostic PET/CT 68Ga-peptide images demonstrate a significant uptake in the tumour, according to the adapted Krenning Scale. Only patients with a greater caption (Grade 3 or 4) in most of the lesions will be admitted.
- Patients with progressive disease in pre-study period (PD within the last 12 months), refractory to conventional standard treatments; clinical progression is allowed.
Key exclusion criteria (11 listed)
- Patients treated with chemotherapy and therapeutic radiotherapy within 4 weeks and treated within 2 weeks with palliative radiotherapy, hormonal or biological therapy.
- Known hypersensitivity to lutetium-177 (177Lu), edotreotide, DOTA or components of the formulation or other radiolabeled peptide agents.
- Known hypersensitivity to lysine, arginine, or any excipient of the nephroprotective aminoacids given concurrently with the lutetium (177Lu) edotreotide infusion;
- Patients treated with prior external beam radiation therapy (EBRT) to more than 25% of the bone marrow.
- Patients treated with previous PRRT with an absorbed dose to the kidney more than 23 Gy and more than 1.8 Gy for the bone marrow or as surrogate of dosimetry (13).
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 |
|---|---|---|
| 177Lu-DOTATOCAdministration of 4 cycles of therapy with 7.4 Gbq Dose for No risk factors Arm and 5.5 Gbq Dose for Risk Factor Arm. Both through slow intravenous infusion in 30 minutes with a dedicated pump system. | Drug | 5.5 Gbq Dose, 7.4 Gbq Dose |
Primary outcome
Efficacy as Disease control rate (DCR)
Time frame: 32 months
percentage of patients who have achieved complete response, partial response, stable disease (according to RECIST 1.1) at the 1st planned evaluation.
4 secondary outcomes
(Safety) percentage of patients who experience acute toxicity
Time frame: 37 months
Progression free survival
Time frame: 44 months
Overall survival
Time frame: 44 months
Quality of life
Time frame: 32 months
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 13 Aug 2024.
Related trials for Neuroendocrine Tumors
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingPhase 1/2
Hepzato Kit and Opdualag for Metastatic Melanoma and Liver Metastasis
Metastatic Melanoma, Liver Metastases
Not yet recruitingObservational study
Clinical Genetics Branch Eligibility Screening Survey
Melanoma, Li-Fraumeni Syndrome
RecruitingPhase 4
Safety and Efficacy of Belzutifan in Preoperative Preparation for Patients With Pheochromocytoma/Paraganglioma (PPGL)
Pheochromocytoma and Paraganglioma (PPGL)
RecruitingPhase 1
A Study of BI 3810944 in Patients With Advanced Cancer
Solid Tumours, Melanoma
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.
Maddalena Sansovini study chair
IRCCS IRST
Federica Matteucci principal investigator
IRCCS IRST
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 177Lu-DOTATOC in people with Neuroendocrine Tumors and Paraganglioma, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 2 sites in Italy.
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 11 inclusion and 11 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 13 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. 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 Oriana Nanni (+390543739266, oriana.nanni@irst.emr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy as Disease control rate (DCR) (time frame: 32 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Aug 2024.