The purpose of this study is to evaluate the effect of PRRT with 177Lu-octreotate on circulating NET transcriptomes. In particular, the variation of circulating NEN transcripts will be correlated to the response to PRRT to test whether this analysis…
ID
Source
Brief title
Condition
- Endocrine neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Significant changes in levels of circulating NEN transcripts during and after
treatment with PRRT utilizing 177Lu-octreotate
- Significant relation between final tumor response to PRRT and changes in
levels of circulating NEN transcripts
- To identify if variations in levels of circulating NEN transcripts may
constitute as an early predictive marker for response to PRRT
Secondary outcome
Not applicable
Background summary
Treatment of Neuroendocrine Tumors (NETs) using PRRT is valuable and takes
about 6 months to complete the intended 4 cycles with 177Lu-Octreotate. There
is a lack of an adequate blood marker which can be used as indicator for tumor
response between the different cycles of PRRT. Currently Chromogranine A (CgA)
is used as marker, however, there is no 1:1 correlation with tumor response and
it is not uncommon to see an elevation of the CgA levels after the start with
PRRT. Normally, the response evaluation via CT-/MRI-scan takes place after
finishing all the intended cycles with PRRT. Especially for patients who are
not responding to treatment with PRRT it is important that they can switch to
another form of therapy in an early stage to prevent any delay in further
treatment.
Transcriptome analysis with the PCR technique in the treatment of NETs with
biotherapy or surgery demonstrated that this test can differentiate between
treated and untreated GEP-NETs (sensitivity and specificity 85-96%), determine
whether a patient has residual disease (100%), determine if a patients can be
categorized as clinically stable following surgery or LAR therapy (90-95%
correct), exhibits progressive or non-responsive disease (75% correct).
Preliminary results demonstrated a clear superiority of this test compared to
conventional CgA assay.
We expect to find a comparable sensitivity, specificity, PPV and NPV also in
the assessment of patients treated with PRRT.
Study objective
The purpose of this study is to evaluate the effect of PRRT with
177Lu-octreotate on circulating NET transcriptomes. In particular, the
variation of circulating NEN transcripts will be correlated to the response to
PRRT to test whether this analysis may constitute an early predictive marker.
Study design
International multi-centre observational study.
A consortium was formed named *LuGenIum Consortium* with the following
participating medical centers:
- Erasmus Medical Centre Rotterdam, the Netherlands
- European Institute of Oncology Milan, Italy
- Zentralklinik Bad Berka, German
Study burden and risks
A vena puncture has been considered as diagnostic tool with minimal side
effects. Participation in this study is associated with a minimal risk and
burden for patients, because;
- New for the patient is that according the protocol extra 10ml blood will be
collected at three time points around the infusion of PRRT. The patient will be
hospitalized for 24 hours for administration of the PRRT, during this
hospitalization the blood samples will be collected.
- During regular follow-up after completion of treatment with PRRT blood is
collected as a procedure of standard care and an extra amount of 10ml will be
drawn. No extra moment of blood collection will be introduced during the
follow-up.
- Patient is not required to invest extra time during, like visiting the
outpatient clinic, when participating in the study.
- Possible risks associated with a venipuncture are minimal
Because of the observational design of the study no negative side effects can
be expected.
s'-Gravendijkwal 230
Rotterdam 3015 CE
NL
s'-Gravendijkwal 230
Rotterdam 3015 CE
NL
Listed location countries
Age
Inclusion criteria
Patient is affected by an inoperable Neuroendocrine Tumor and eligible for treatment with PRRT based on the following criteria:;- The capacity to understand and willingness to sign an informed consent form, obtained prior to enrolment into the study;And meets the standard conditions for treatment with PRRT:
- Presence of histology proven GEP tumor(s), including bronchial carcinoids
- Presence of somatostatin-receptors on the known tumor lesions demonstrated by OctreoScan® within 6 months of the first dose of radiolabelled octreotate/octreotide. The uptake on the OctreoScan® should be at least as high as normal liver uptake on planar imaging
- Life expectancy greater than 12 weeks
- Serum creatinine <=150 µmol/liter or 1.7 mg/dL, and a measured creatinine clearance (or measured GFR using plasma clearance methods, not gamma-camera based) of >=50 mL/min
- Hemoglobin (HgB) concentration >=5.5 mmol/L (>=8.9 g/dL); WBC >=2.0*109/L (2000/mm3); platelets >=75*109/L (75*103/mm3)
- Total bilirubin <=3 x ULN
- Serum albumin >30 g/L, or serum albumin <=30 g/L but normal prothrombin time
- Karnofsky Performance Status >=60
- Presence of at least 1 measurable site of disease
Exclusion criteria
Patient is not eligible for PRRT or an alternative treatment is available:;A potential subject who meets any of the standard contraindications for treatment with PRRT will not be able to participate in this study:
- Possible surgery with curative intent
- Surgery, radiotherapy, chemotherapy or other investigational therapy within 3 months of
the start of therapy
- Patients with known brain metastases unless these metastases have been treated and
stabilized for at least six months prior to study start. Patients with a history of brain
metastases must have a head CT with contrast to document stable disease prior to study
start
- Uncontrolled congestive heart failure
- Any subject who is taking concomitant medications which decrease renal function
- Any subject receiving therapy with somatostatin analogues in whom these analogues cannot be interrupted for 12 hours before and 12 hours after the administration of the radiolabelled somatostatin analogues, or any subject receiving therapy with long-acting somatostatin analogues in whom these analogues cannot be interrupted for at least 6 weeks before the administration of the radiolabelled somatostatin analogues, unless the uptake on the OctreoScan® during continued somatostatin analogue medication is at least as high as normal liver uptake on planar imaging
- In patients with unusual haematological parameters, including an increased MCV
(>105fL), and especially in those who had previous chemotherapy, the advice of a hematologist should be seeked, for adequate further work up
- Subjects with another significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study.
- Pregnancy
- Prior radiation therapy to more than 25% of the bone marrow
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL48623.078.14 |