Neuroendocrine TumorsPhase 1/2LuXNCT02736500
Peptide Receptor Radionuclide Therapy With 177Lu-Dotatate Associated With Metronomic Capecitabine In Patients Affected By Aggressive Gastro-Etero-Pancreatic Neuroendocrine Tumors
A Phase 1/2 study testing 28 GBq 177Lu-DOTATATE and 22 GBq 177Lu-DOTATATE in people with Neuroendocrine Tumors and Gastro Entero Pancreatic Neuroendocrine Tumors, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 2 sites in Italy.
Trial summary
The aim of this phase I-II study is to evaluate the efficacy and toxicity of PRRT with 177Lu-DOTATATE (Lu-PRRT) associated to metronomic chemotherapy with Capecitabine in patients affected by aggressive FDG-positive gastro-entero-pancreatic NET. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuroendocrine Tumors, Gastro Entero Pancreatic Neuroendocrine Tumors
- What is being tested?
- 28 GBq 177Lu-DOTATATE and 22 GBq 177Lu-DOTATATE
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 2 sitesItaly
- Study dates
- 2 Sep 2015to 22 Oct 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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
- Histopathologic diagnosis of inoperable or metastatic gastro-entero-pancreatic neuroendocrine neoplasia.
- Conserved hematological, liver and renal parameters: haemoglobin >= 10 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 <2.5 X UNL (< 5 X UNL in presence of liver metastases), creatinine < 2 mg/dL.
- Age more than 18 years.
- Patients with documented disease will be admitted to therapeutic phase only if the diagnostic receptor imaging (OctreoScan) demonstrate a significant uptake in the tumor (grade 2 or 3, according to a preset scoring, where grade 1= equal to normal liver, grade2 = higher than normal liver, grade 3= higher than kidneys and spleen), that may allow delivering a low absorbed dose to normal organs and a high dose to the tumor.
- Patients with documented disease will be admitted to therapeutic phase only if the 18FDG PET/CT is positive with a SUV > 2.5 at least in one documented lesion.
- Disease must be measurable by means of conventional imaging (CT or MRI).
Show all 9Show fewer
- Before treatment clinical history data will be collected, physical examination will be performed and diagnostic and laboratory data will be examined.
- Patients must not receive other treatments (e.g. chemo- or radiotherapy) from one month before to two months after the completion of 177Lu-DOTATATE cycles.
- Patients must be naive from previous radionuclide treatments with radiopeptides (e.g. 111Inpentetreotide, 90Y-DOTATOC) or other radiopharmaceuticals (e.s. 131I-MIBG, 131I).
Who cannot join
- Pregnancy/breastfeeding (a pregnancy test not older than 7 days is mandatory).
- Assessed bone marrow invasion > 25%.
- Other concomitant neoplasm (excluding in situ basaliomas and radically treated cervical cancers).
- ECOG score higher than 2.
- Expectancy of life shorter than 6 months.
- Patients with psycho-physical conditions that are not suitable for entering this clinical study and fulfilling its requirements.
Trial locations and contacts
2 sites in 1 country.
About this study
The aim of this phase I-II study is to evaluate the efficacy and toxicity of PRRT with 177Lu-DOTATATE (Lu-PRRT) associated to metronomic chemotherapy with Capecitabine in patients affected by aggressive FDG-positive gastro-entero-pancreatic NET. Moreover to analyze the effects of the capecitabine metronomic schedule on the level of circulating angiogenetic factors.
Read the detailed description
Neuroendocrine tumors (NETs) are relatively rare tumors, mainly originating from the digestive system, able to produce bioactive amines and hormones. NETs tend to be slow growing and are often diagnosed when metastatic. Treatment is multidisciplinary and should be individualized according to the tumor type, burden, and symptoms. Therapeutic tools include surgery, interventional radiology, and medical treatments such as somatostatin analogues, interferon, chemotherapy, new targeted drugs (everolimus, sunitinib) with radiolabelled somatostatin analogues. Despite the options available, antiproliferative treatment options for patients with inoperable gastro-entero-pancreatic (GEP) NETs are limited.
PRRT with radiolabelled somatostatin analogues 90Y-DOTATOC, and 177Lu-DOTATATE (177Lu-DOTA-D-Phe1-Tyr3-octreotate), has been experimented for more then 15 years in few centers. The introduction of PRRT and, particularly, the advent of 177Lu-DOTATATE, broke through the poor scenario of available treatment for NETs.
Dosimetric studies demonstrated that 90Y-DOTATOC and 177Lu-DOTATATE are able to deliver high radiation doses to somatostatin receptor sst2-expressing tumors and low doses to normal organs. Clinical studies demonstrated that partial and complete objective responses in up to 30% of patients can be obtained, with a great survival benefit including those with stable disease. Side effects may involve the kidney and the bone marrow and are usually mild. Renal protection is used to minimize the risk of a late decrease of renal function.
Recently, in order to further increase the objective response to PRRT, a combined treatment with the radiosensitizer capecitabine, has been proposed and tested on GEP-NET patients' population. Capecitabine is the oral prodrug of 5-fluorouracile (5-FU), which is active in GEP tumors and a radiosensitizer itself. The finding that neo-angiogenesis can be shut down also with cytotoxic drugs like capecitabine when administered in low and frequent doses, constitutes the rationale for proposing a particular schedule of chemotherapy that is, therefore, named "metronomic" or "anti-angiogenic".
Based on the reported experience, the investigators think to offer a combined therapy in aggressive, metabolically active tumors, such as those patients with a positive FDG scan. FDG-PET allow the investigators to obtain in vivo imaging of increased glycolysis which is known to be an hallmark of tumor aggressiveness.
The aim of this phase I-II study is to evaluate the efficacy and toxicity of PRRT with 177Lu-DOTATATE (Lu-PRRT) associated to metronomic chemotherapy with Capecitabine in patients affected by aggressive FDG-positive gastro-entero-pancreatic NET. Moreover to analyze the effects of the capecitabine metronomic schedule on the level of circulating angiogenetic factors.
- Being tested
- 28 GBq 177Lu-DOTATATE, 22 GBq 177Lu-DOTATATE
- Keywords
- neuroendocrine tumors, gastro entero pancreatic neuroendocrine tumors, Radioisotope therapy, 177Lu-DOTATATE, METRONOMIC CAPECITABINE
- Medical subject headings
- Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
28 GBq 177Lu-DOTATATEDrug
Patients without risk factors (particularly long standing and poorly controlled diabetes and hypertension) for late renal toxicity will be administered with 5 cycles of 5.5 GBq (150 mCi) each, up to the total cumulative activity of 28 GBq (750 mCi) of 177Lu-DOTATATE.
22 GBq 177Lu-DOTATATEDrug
Patients with risk factors for late renal toxicity will be administered with 6 cycles of 3.7 GBq (100 mCi) each, up to the total cumulative activity of 22 GBq (600 mCi)177Lu-DOTATATE
| Study group | Role | What they receive |
|---|---|---|
| 28 GBq 177Lu-DOTATATE | Experimental | 5 cycles of 5.5 GBq (150 mCi) each, up to the total cumulative activity of 28 GBq (750 mCi) 177Lu-DOTATATE Receives: Drug: 28 GBq 177Lu-DOTATATE |
| 22 GBq 177Lu-DOTATATE | Experimental | 6 cycles of 3.7 GBq (100 mCi) each, up to the total cumulative activity of 22 GBq (600 mCi) 177Lu-DOTATATE Receives: Drug: 22 GBq 177Lu-DOTATATE |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Overall Response Rate
rate of objective clinical response (complete response (CR), partial response (PR), or minor response (MR) according to RECIST criteria
Measured: up to 24 months
toxicity rate
The rate of toxicity, either acute or delayed, according to NCI criteria, of the association 177Lu-DOTATATE and metronomic capecitabine.
Measured: up to 24 months
Secondary outcomes (2)
Progression free survival in association with histopathology characteristics
evaluation of the PFS and the possible association between histopathology characteristics (grading and proliferation index)
Measured: up to 24 months
Progression free survival in association with the receptor and metabolic status at OctreoScan and FDG PET
Progression free survival in association with the receptor and metabolic status at OctreoScan and FDG PET
Measured: up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2016 (estimated)
- Study start2 Sep 2015
- Primary completionApr 2017
- Study completion22 Oct 2019
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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
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
- Collaborators
- Istituto Europeo di Oncologia
- Responsible party
- Sponsor
- Investigators
- Giovanni Paganelli, MD, Principal investigator, IRST IRCCS, Meldola (FC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02736500
- Sponsor's protocol ID
- IRST100.19
- Acronym
- LuX
- Status last verified
- Jan 2025
- First submitted
- 7 Apr 2016
- Last updated
- 13 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Peptide Receptor Radionuclide Therapy With 177Lu-Dotatate Associated With Metronomic Capecitabine In Patients Affected By Aggressive Gastro-Etero-Pancreatic Neuroendocrine Tumors
- ClinicalTrials.gov ID
- NCT02736500
- Acronym / sponsor ID
- LuX / IRST100.19
- Keywords
- neuroendocrine tumors, gastro entero pancreatic neuroendocrine tumors, Radioisotope therapy, 177Lu-DOTATATE, METRONOMIC CAPECITABINE
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCSUniversity, hospital or other
- Collaborators
- Istituto Europeo di Oncologia
- Study start
- 2 Sep 2015 (actual)
- Primary completion
- Apr 2017 (actual)
- Study completion
- 22 Oct 2019 (actual)
- First posted
- 13 Apr 2016 (estimated)
- 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.
The aim of this phase I-II study is to evaluate the efficacy and toxicity of PRRT with 177Lu-DOTATATE (Lu-PRRT) associated to metronomic chemotherapy with Capecitabine in patients affected by aggressive FDG-positive gastro-entero-pancreatic NET. Moreover to analyze the effects of the capecitabine metronomic schedule on the level of circulating angiogenetic factors.
Detailed description
Neuroendocrine tumors (NETs) are relatively rare tumors, mainly originating from the digestive system, able to produce bioactive amines and hormones. NETs tend to be slow growing and are often diagnosed when metastatic. Treatment is multidisciplinary and should be individualized according to the tumor type, burden, and symptoms. Therapeutic tools include surgery, interventional radiology, and medical treatments such as somatostatin analogues, interferon, chemotherapy, new targeted drugs (everolimus, sunitinib) with radiolabelled somatostatin analogues. Despite the options available, antiproliferative treatment options for patients with inoperable gastro-entero-pancreatic (GEP) NETs are limited.
PRRT with radiolabelled somatostatin analogues 90Y-DOTATOC, and 177Lu-DOTATATE (177Lu-DOTA-D-Phe1-Tyr3-octreotate), has been experimented for more then 15 years in few centers. The introduction of PRRT and, particularly, the advent of 177Lu-DOTATATE, broke through the poor scenario of available treatment for NETs.
Dosimetric studies demonstrated that 90Y-DOTATOC and 177Lu-DOTATATE are able to deliver high radiation doses to somatostatin receptor sst2-expressing tumors and low doses to normal organs. Clinical studies demonstrated that partial and complete objective responses in up to 30% of patients can be obtained, with a great survival benefit including those with stable disease. Side effects may involve the kidney and the bone marrow and are usually mild. Renal protection is used to minimize the risk of a late decrease of renal function.
Recently, in order to further increase the objective response to PRRT, a combined treatment with the radiosensitizer capecitabine, has been proposed and tested on GEP-NET patients' population. Capecitabine is the oral prodrug of 5-fluorouracile (5-FU), which is active in GEP tumors and a radiosensitizer itself. The finding that neo-angiogenesis can be shut down also with cytotoxic drugs like capecitabine when administered in low and frequent doses, constitutes the rationale for proposing a particular schedule of chemotherapy that is, therefore, named "metronomic" or "anti-angiogenic".
Based on the reported experience, the investigators think to offer a combined therapy in aggressive, metabolically active tumors, such as those patients with a positive FDG scan. FDG-PET allow the investigators to obtain in vivo imaging of increased glycolysis which is known to be an hallmark of tumor aggressiveness.
The aim of this phase I-II study is to evaluate the efficacy and toxicity of PRRT with 177Lu-DOTATATE (Lu-PRRT) associated to metronomic chemotherapy with Capecitabine in patients affected by aggressive FDG-positive gastro-entero-pancreatic NET. Moreover to analyze the effects of the capecitabine metronomic schedule on the level of circulating angiogenetic factors.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 28 GBq 177Lu-DOTATATE | Experimental | Drug: 28 GBq 177Lu-DOTATATE5 cycles of 5.5 GBq (150 mCi) each, up to the total cumulative activity of 28 GBq (750 mCi) 177Lu-DOTATATE |
| 22 GBq 177Lu-DOTATATE | Experimental | Drug: 22 GBq 177Lu-DOTATATE6 cycles of 3.7 GBq (100 mCi) each, up to the total cumulative activity of 22 GBq (600 mCi) 177Lu-DOTATATE |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histopathologic diagnosis of inoperable or metastatic gastro-entero-pancreatic neuroendocrine neoplasia.
- Conserved hematological, liver and renal parameters: haemoglobin >= 10 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 <2.5 X UNL (< 5 X UNL in presence of liver metastases), creatinine < 2 mg/dL.
- Age more than 18 years.
- Patients with documented disease will be admitted to therapeutic phase only if the diagnostic receptor imaging (OctreoScan) demonstrate a significant uptake in the tumor (grade 2 or 3, according to a preset scoring, where grade 1= equal to normal liver, grade2 = higher than normal liver, grade 3= higher than kidneys and spleen), that may allow delivering a low absorbed dose to normal organs and a high dose to the tumor.
- Patients with documented disease will be admitted to therapeutic phase only if the 18FDG PET/CT is positive with a SUV > 2.5 at least in one documented lesion.
Key exclusion criteria (6 listed)
- Pregnancy/breastfeeding (a pregnancy test not older than 7 days is mandatory).
- Assessed bone marrow invasion > 25%.
- Other concomitant neoplasm (excluding in situ basaliomas and radically treated cervical cancers).
- ECOG score higher than 2.
- Expectancy of life shorter than 6 months.
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 |
|---|---|---|
| 28 GBq 177Lu-DOTATATEPatients without risk factors (particularly long standing and poorly controlled diabetes and hypertension) for late renal toxicity will be administered with 5 cycles of 5.5 GBq (150 mCi) each, up to the total cumulative activity of 28 GBq (750 mCi) of 177Lu-DOTATATE. | Drug | 28 GBq 177Lu-DOTATATE |
| 22 GBq 177Lu-DOTATATEPatients with risk factors for late renal toxicity will be administered with 6 cycles of 3.7 GBq (100 mCi) each, up to the total cumulative activity of 22 GBq (600 mCi)177Lu-DOTATATE | Drug | 22 GBq 177Lu-DOTATATE |
Primary outcome
Objective Overall Response Rate
Time frame: up to 24 months
rate of objective clinical response (complete response (CR), partial response (PR), or minor response (MR) according to RECIST criteria
toxicity rate
Time frame: up to 24 months
The rate of toxicity, either acute or delayed, according to NCI criteria, of the association 177Lu-DOTATATE and metronomic capecitabine.
2 secondary outcomes
Progression free survival in association with histopathology characteristics
Time frame: up to 24 months
Progression free survival in association with the receptor and metabolic status at OctreoScan and FDG PET
Time frame: up to 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2025.
Related trials for Neuroendocrine Tumors
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
RecruitingPhase 2
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Carcinoma, Neuroendocrine, Tumor, Neuroendocrine
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 3
Somatostatin Analogues vs. Observation After Peptide Receptor Radionuclide Therapy (PRRT) in Nonfunctional Neuroendocrine Neoplasms
Neuroendocrine Neoplasm, Gastroenteropancreatic Neuroendocrine Neoplasm
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. This study is not recruiting at the moment.
Giovanni Paganelli, MD principal investigator
IRST IRCCS, Meldola (FC)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 28 GBq 177Lu-DOTATATE and 22 GBq 177Lu-DOTATATE in people with Neuroendocrine Tumors and Gastro Entero Pancreatic Neuroendocrine Tumors, 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 9 inclusion and 6 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: finished, as of the sponsor's last update on 13 Jan 2025. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Overall Response Rate (time frame: up to 24 months). The study lists 2 primary outcomes in all. 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 Jan 2025.