177Lutetium-octreotate Treatment Prediction Using Multimodality Imaging in Refractory NETs
Conditions
Gastroenteropancreatic Neuroendocrine Tumors
Conditions: official terms
Apudoma - Carcinoid Tumor - Intestinal Neoplasms - Neuroendocrine Tumors - Pancreatic Neoplasms - Stomach Neoplasms
Conditions: Keywords
Peptide Receptor Radionuclide Therapy (PRRT), Neuroendocrine Tumors
Study Type
Interventional
Study Phase
Phase 3
Study Design
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: intravenous injection of 177Lu-octreotate
Type: Drug
Overall Status
Recruiting
Summary
The purpose of this study is to determine if 68Gallium-octreotate and 18Fluorodesoxyglucose uptake, apparent diffusion coefficient and post 177Lu-octreotate SPECT/CT dosimetry are reliable predictors for lesion-by-lesion treatment outcome.
Detailed Description
This is a feasibility study evaluating the use of 177Lutetium-octreotate in the treatment of advanced refractory Neuroendocrine Tumors.

Objectives of the study:

1. primary (on a lesion basis): To assess the value of the following parameters (obtained through functional and molecular imaging) for predicting the lesion-by-lesion PRRT treatment outcome:

- 18FDG uptake on 18FDG PET/CT

- 68Ga-octreotate uptake on 68Ga-octreotate PET/CT

- Apparent diffusion coefficient on diffusion weighted MRI (for these 3 parameters, absolute values at baseline and after each cycle will be assessed, as well as their relative differences)

- Tumor dosimetry on post 177Lu-octreotate SPECT/CT after each cycle.

2. secondary (on a patient basis): To generate a patient-based response model based on the aforementioned parameters.

Treatment will consist of 177Lu-octreotate injections in fixed activities of 7,4 GigaBecqurel each, given 11-13 weeks apart, injected intravenously with simultaneous infusion of an amino acid solution. (Before amino acid nephroprotection, ondansetron, methylprednisolone and metoclopramid, are given intravenously in order to prevent nausea or vomiting). Approximately 30 min after the beginning of the amino acid solution, 177Lu-octreotate is co-infused over 15-30 minutes. The amino acid infusion is continued at the same rate for 3-5 more hours (total infusion lasts 4-6 hours).

In total, 4 cycles are planned. However, the total number of administered cycles will be limited by critical organ (kidneys and bone marrow) cumulated absorbed doses.

Treatment efficacy will be assessed:

- on a lesion-basis (change of longest transversal diameter).

- on a patient-basis using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

1. Patient-based

- Age above 18 years.

- Histology-proven advanced Gastroenteropancreatic-Neuroendocrine tumors.

- Disease progression defined as follows (at least one of the following):

- Radiological progression (according to RECIST 1.1) on an MRI or CT over the last 12 months

- Progression on a somatostatin receptor-imaging, PET/CT or SPECT/CT over the last 12 months [apparition of new lesion(s) or increase in the transaxial axis size of more than 30% on the same imaging modality]

- Both of the following criteria (a+b):

1. clinical progression:

1. sustained (for more than 2 weeks) increase of NET-specific hormonal hypersecretion related symptom frequency by 50% or,

2. sustained (for more than 2 weeks) increase of severity by 1 grade (according to CTCAE version 4.03).

2. biochemical progression: by increase of NET-specific tumoral markers (plasma Chromogranin A, plasma NSE, urine 5-HIAA or other) in two consecutive measurements.

- Disease refractory to somatostatine analogues and/or standard systemic therapy available in Belgium at the time of inclusion criteria.

- Adequate renal function with GFR≥50 mL/min/1.73m2 (evaluated by 51Cr-EDTA test).

- Adequate bone marrow function with Hemoglobin≥9 g/dL; WBC≥2000/μL; platelet count≥100000/μL.

- Adequate liver function with total bilirubin ≤2 x upper limit of normal (ULN) and transaminases ≤5 x ULN., serum albumin>3,0gr/dL with normal prothrombin time (>70%).

- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.

- Women of childbearing potential and men must agree to use a highly‐effective form of contraception for the duration of study participation and up to six months after the end of the treatment. A serum pregnancy test will also be performed prior inclusion.

- Patient's written informed consent obtained prior to any study procedure.

2. Lesion-based: The patient must have at least one target lesion fulfilling all of the below criteria:

- On the 68Ga-octreotate PET/CT (performed within a period of 3 weeks after signature of the informed consent form): tumoral uptake higher than the physiological liver uptake (grade III or IV of the Rotterdam visual score) in a lesion with longest axis diameter ≥20mm (measured on PET/CT);

- At least one of these lesions morphologically measurable according RECIST 1.1 and progressive on the MRI (or CT if MRI is not applicable);

- Target lesion should not have been previously irradiated.

Exclusion Criteria:

- Possible surgery with curative intent.

- Surgery, radiotherapy, chemotherapy, within the last 6 weeks.

- Diffuse bone marrow infiltration on 68Ga-octreotate PET/CT confirmed by MRI.

- Patients with known uncontrolled brain metastases.

- Short-acting somatostatin analogues not interrupted for 24 hours before or long-acting somatostatin not interrupted for at minimum of 4 weeks before therapy.

- Subjects with another significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the investigator's opinion, may interfere with completion of the study.

- Pregnancy. Women of child-bearing potential refusing an adequate contraception.
Location
Jules Bordet Institute
Brussels, Belgium
Status: Recruiting
Start Date
May 2013
Completion Date
May 2016
Sponsors
Jules Bordet Institute
Source
Jules Bordet Institute
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page