Peptide Receptor Radionuclide Therapy With 177Lu-Dotatate Associated With Metronomic Capecitabine In Patients Affected By Aggressive Gastro-Etero-Pancreatic Neuroendocrine Tumors

NCT02736500 | Completed Phase 1

• 1 other identifier: IRST100.19
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

Brief 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. Moreover to analyze the effects of the capecitabine metronomic schedule on the level of circulating angiogenetic factors.

Conditions

Neuroendocrine Tumors; Gastro Entero Pancreatic Neuroendocrine Tumors

Keywords

neuroendocrine tumors; gastro entero pancreatic neuroendocrine tumors; Radioisotope therapy; 177Lu-DOTATATE; METRONOMIC CAPECITABINE

Outcome Measures

Primary Outcomes (2)

• Objective Overall Response Rate

  rate of objective clinical response (complete response (CR), partial response (PR), or minor response (MR) according to RECIST criteria

  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.

  up to 24 months

Secondary Outcomes (2)

• Progression free survival in association with histopathology characteristics

  up to 24 months

• Progression free survival in association with the receptor and metabolic status at OctreoScan and FDG PET

  up to 24 months

Study Arms (2)

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

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

Drug: 22 GBq 177Lu-DOTATATE

Interventions

28 GBq 177Lu-DOTATATE DRUG

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.

28 GBq 177Lu-DOTATATE

22 GBq 177Lu-DOTATATE DRUG

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

22 GBq 177Lu-DOTATATE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS: lead
• Istituto Europeo di Oncologia: collaborator

Study Sites (2)

Giovanni Paganelli

Meldola, FC, 47014, Italy

Location

Lisa Bodei

Milan, Italy

Location

MeSH Terms

Conditions

Neuroendocrine Tumors

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• Giovanni Paganelli, MD

  IRST IRCCS, Meldola (FC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2016
• First Posted: April 13, 2016
• Study Start: September 2, 2015
• Primary Completion: April 1, 2017
• Study Completion: October 22, 2019
• Last Updated: January 13, 2025

Record last verified: 2025-01

Locations

IT (2)