Peptide Receptor Radionuclide Therapy With 177Lu-Dotatate Associated With Metronomic Capecitabine In Patients Affected By Aggressive Gastro-Etero-Pancreatic Neuroendocrine Tumors (LuX)
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|ClinicalTrials.gov Identifier: NCT02736500|
Recruitment Status : Active, not recruiting
First Posted : April 13, 2016
Last Update Posted : April 21, 2020
|Condition or disease||Intervention/treatment||Phase|
|Neuroendocrine Tumors Gastro Entero Pancreatic Neuroendocrine Tumors||Drug: 28 GBq 177Lu-DOTATATE Drug: 22 GBq 177Lu-DOTATATE||Phase 1 Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||37 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Peptide Receptor Radionuclide Therapy With 177Lu-Dotatate Associated With Metronomic Capecitabine In Patients Affected By Aggressive Gastro-Etero-Pancreatic Neuroendocrine Tumors|
|Actual Study Start Date :||September 2, 2015|
|Actual Primary Completion Date :||July 2018|
|Estimated Study Completion Date :||June 2020|
Experimental: 28 GBq 177Lu-DOTATATE
5 cycles of 5.5 GBq (150 mCi) each, up to the total cumulative activity of 28 GBq (750 mCi) 177Lu-DOTATATE
Drug: 28 GBq 177Lu-DOTATATE
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.
Experimental: 22 GBq 177Lu-DOTATATE
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
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
- 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.
- Progression free survival in association with histopathology characteristics [ Time Frame: up to 24 months ]evaluation of the PFS and the possible association between histopathology characteristics (grading and proliferation index)
- Progression free survival in association with the receptor and metabolic status at OctreoScan and FDG PET [ Time Frame: up to 24 months ]Progression free survival in association with the receptor and metabolic status at OctreoScan and FDG PET
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02736500
|Meldola, FC, Italy, 47014|
|Principal Investigator:||Giovanni Paganelli, MD||IRST IRCCS, Meldola (FC)|