Neuroendocrine TumorsPhase 2POLNETS_PRRTNCT04029428

Peptide Receptor Radionuclide Therapy in the Treatment of Advanced, Non-resectable and/or Symptomatic Tumors With SSTR Overexpression

A Phase 2 study testing 90Y-DOTATATE, (177Lu-DOTAOTyr3)Octreotate and 90Y DOTATATE and 177Lu DOTATATE (mix each of 50%) in people with Neuroendocrine Tumors, run by University of Warmia and Mazury at 1 site in Poland.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 85 years
Conditions the study is for: Neuroendocrine Tumors
What is being tested?: 90Y-DOTATATE, (177Lu-DOTAOTyr3)Octreotate and 90Y DOTATATE and 177Lu DOTATATE (mix each of 50%)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 150 participants
Where: 1 sitePoland
Study dates: 2 Nov 2004to 1 Jan 2021
Phase: Phase 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 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Adults ≥18 years old, male or female, with histologically proven, well-differentiated G1/2 GEP-NET, BPCs, PPGLs or NET (cancer with unknown primary - CUP), with Ki-67 <20%, in selected cases patients with NETG3 will be included if there will be reported well/moderate morphological appearance but Ki-67>20% but less then Ki<30%; and there will be high expression of somatostatin receptor seen in functional imaging utilized functional imaging 99mTc HYNICTOC or 68Ga DOTATATE or 68Ga DOTATOC.
The presence of high expression of somatostatin receptors demonstrated on Somatostatin Receptor Imaging using 99mTc HYNICTOC (SPECT) or 68Ga DOTATATE or 68Ga DOTATOC (PET) scans, et least as uptake in not involved liver, Krenning >2
Non-resectable, advanced determined by an appropriately specialized surgeon or deemed not suitable for liver directed therapies where liver is the only site of disease;
Performance status (PS) based on ECOG 0-2;
Unresectable, advanced/metastatic progressive disease evaluated as clinical, biochemical, bad control symptoms of tumour hypersecretion or disease progression seen in imaging structural or functional.
Adequate renal function (measured creatinine clearance > 30 ml/min by DTPA or eGFR),

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Adequate bone marrow function (Hb>8 g/d/L, WBC>2.0 x109L, ACN>1.5 x109L and PLT>80 x 103/L);
Adequate liver function (serum total bilirubin ≤ 1.5 x ULN, and Alanine aminotransferase (ALAT), Aspartate aminotransferase (ASPAT), Alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver metastases)). INR ≤ 1.5 (or on a stable dose of LMW heparin for >2 weeks at time of enrollment);
Life expectancy of at least 6 months;
The tumor parameters that can be measured objectively as the size to be assessed in radiological studies on the basis of the RECIST 1.0;
In the absence of the ability to measure tumor size based on RECIST criteria, they have tumor parameters that can be measured objectively as tumor markers determined in the blood or urine CgA, 5HIAA.
Study treatment both planned and able to start within 28 days of inclusion;
Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments;
Signed, written informed consent.

Who cannot join

• Primary non-NETs;
Cytotoxic chemotherapy e.g. CAPTEM, or any other type of chemotherapy recorded 6 weeks before enrollment into the study;
Any type of biotherapy using somatostatin analogues or any targeted therapy within the last four weeks;
Pre-existing locoregional treatment such as radiomebolization (SIR-spheres) or HDR brachytherapy under CT control, performed in the last 6 months;
Major surgery/surgical therapy for any cause within two months before start of PRRT;
Surgical therapy of loco-regional metastases within the last three months prior to inclusion;

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Uncontrolled metastases to the central nervous system, in the case of surgical and / or radiotherapeutic treatment, patients should remain on a stable dose of steroids for at least 2 weeks before enrollment, without deterioration of the general state associated with the presence of metastatic disease in the CNS;
Poorly controlled concurrent medical illness. E.g. unstable diabetes with glycosylated hemoglobin (HbA1c> 9.0), the optimal glycaemic control should be achieved before starting trial therapy);
Symptomatic heart failure NYHA class III or IV, congestive cardiac failure, myocardial infarction in the last 6 months, serious uncontrolled cardiac arrhythmia, unstable angina, or other serious cardiac problems;
Active uncontrolled infection, including Hepatitis and Hepatitis, HIV, in the case of HCV and HBV infection, the patient can be included in the study confirming the suppression of viral replication and the patient remains on the correct therapeutic dose of antiviral drugs;
Pregnant patients (a negative pregnancy test is required);
Women of childbearing age must present a negative pregnancy test at the beginning of the study and must use double barrier to contraception. Women of childbearing age are defined as menopausal if they remain menstrual for at least 1 year, or surgical sterilization or removal of the uterus before the start of the study;
Breast-feeding female patients;
Patients in a mental state who can't understand the nature, extent and possible consequences of participating in the study associated with radioisotope treatment, or there is evidence of a lack of cooperation by the patient;
Exclusive clinical and laboratory findings that may compromise the patient's safety or reduce the chances of obtaining satisfactory data to achieve the goal (s) of the study;
Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse;
The patient may be included in the maintenance treatment if the patient's clinical condition is stable.

Trial locations and contacts

1 site in 1 country.

Jarosław B Ćwikła, MD, PhD contact

+48602112599

jbcwikla@interia.pl

Poland1 site, 1 recruiting

Centrum Diagnostyczno-Lecznicze Gammed
Warsaw, 02-351
Jarosław B Ćwikła, M.D., +48602112599, jbcwikla@interia.pl
Alina Czepukojć, M.Sc., +48228223001 ext. Ćwikła, jbcwikla@interia.pl
Recruiting

Other trials in Poland

About this study

Official title: Clinical Study of the Use of Yttrium-90 (90Y) and/or Lutecium-177 (177Lu) DOTATATE (DOTA-0-Tyr3-Octreotate) in the Treatment of Disseminated and / or Symptomatic Tumors With Somatostatin Receptor Overexpression

This is a non-randomized phase II , open label, comparative study. Patients with advanced non-resectable and/or progressive gastro-entero-pancreatic Neuroendocrine Tumours - GEP-NET, (G1, G2 and G3), Broncho-pulmonary Carcinoids (BPCs Atypical-AC or Typical-TC), pheochromocytoma/paraganglioma (PPGLs) and neuroendocrine tumours of unknown primary (NET-CUP) with overexpression of somatostatin receptor (SSTR positive) will be enrolled in the study and will be treated using Peptide Receptor Radionuclide Therapy (PRRT) initially with Yttrium-90 (90Y) DOTATATE (DOTA-0-Tyr3-Octreotate), and then compare to Lutecium-177 (177Lu) DOTATATE or mix of both Yttrium-90 (90Y) and Lutecium-177 (177Lu) DOTATATE. Total maximum activity for Yttrium-90 up to 4x3,7GBq, for Lutecium-177 up to 4x5,55GBq (Lu-177) and for both (mix) 4x3,7GBq (90Y and 177Lu 50% each).

Read the detailed description

This is a non-randomized phase II, open-label, comparative study. Patients with advanced, unresectable and/or progressive Gastro-Entero-Pancreatic Neuroendocrine Tumors - GEP-NET, (histological grade G1, G2 and G3), Broncho-Pulmonary Carcinoids (BPCs), including typical carcinoid (AC) and typical carcinoid (TC), pheochromocytoma/paragangliomas (PPGLs) and neuroendocrine tumors (cancers) of unknown primary (NET-CUP). All with overexpression of somatostatin receptor (SSTR positive) based on somatostatin receptor imaging (scintigraphy or PET), will be enrolled in this study.

Initially patients will be assigned to single arm of PRRT using yttrium-90 (90Y) DOTATATE (DOTA-0-Tyr3-Octreotate) and then patients will be non-randomly assigned to one of the two groups lutecium-177 (177Lu) DOTATATE or mix yttrium (90Y) DOTATATE and lutecium-177 (177Lu) DOTATATE (50% each). The dosages (total activity used in each group of treated patients will be as follows:

Total activity of 90Y DOTATATE 4x3,7GBq (14,8 GBq) for 4 cycles at 8 ± 2 weeks (400mCi)
Total activity of 177Lu DOTATATE 4x5,55GBq (22,2 GBq for 4 cycles at 8 ± 2 weeks (600 mCi)
Total activity of mix both 90Y DOTATATE and 177Lu DOTATATE (50 each) 4x3,7 GBq for 4 cycles at 8 ± 2 weeks (400mCi).

The non-randomized, phase II study design, allows for proposed initial active treatment arm using standard dose of 90Y DOTATATE and experimental treatment arm which composed of two options of PRRT with lutecium-177 DOTATATE or mix 90Y and 177Lu DOTATATE. The experimental therapy arm will be consisting of randomly allocated patients.

Subjects including in this study will be evaluated in the mixed patients' population, including GEP-NET, bronchopulmonary carcinoid (BPCs), paraganglioma/pheochromocytomas (PPGLs) and NET of unknown origin (NET-CUP).

Estimates of the original goals of the study can be assessed for each scheme separately using a two-step design using an external standard for comparison (the investigator's previous published results include standard PRRT using 90Y DOTATATE in subjects with GEP-NET).

Although the sample size in this study is not based on any specific statistical hypothesis to compare separate groups of patients those with PRRT using 90Y DOTATATE, next those with 177Lu DOTATATE and those who will receive mix 90Y and 177Lu DOTATATE.

This study design allows an objective set of clinical efficacy results in terms of PRRT responses and safety in these three treatment regimens in the same patient population, even different groups of tumors, which may be useful when planning next generation of the clinical trial using PRRT.

Conditions: Neuroendocrine Tumors
Being tested: 90Y-DOTATATE, (177Lu-DOTAOTyr3)Octreotate, 90Y DOTATATE and 177Lu DOTATATE (mix each of 50%)
Keywords: PRRT - Peptide Receptor Radionuclide Therapy,, GEP-NET - Gastro-Entero-Pancreatic Neuroendocrine Tumours;, BPCs - Bronchopulmonary Carcinoids (Atypical & Typical), PPGLs - Pheochromocytomas/Paragangliomas;, NET-CUP - Neuroendocrine Tumours of unknown primary, clinical efficacy, toxcity - adverse events (AEs), OS - overall survival, PFS - progression free survival
Medical subject headings: Neuroendocrine Tumors, Paraganglioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

90Y-DOTATATEDrug
Also called 90Y DOTATATE
Total activity of 90Y DOTATATE, 4x3.7GBq (14.8 GBq). Single session of i.v. infusion of 90Y DOTATATE administered for 20 min via infusion pump with co-infusion of amino-acids solution 1000ml for 1h before and then et least 6h after 90Y DOTATATE infusion. Therapy consists up to 4 cycles at 8 ± 2 weeks between each other.
(177Lu-DOTAOTyr3)OctreotateDrug
Also called 177Lu DOTATATE
Total activity of 177Lu DOTATATE, 4x5.55GBq (22.2 GBq). Single session of i.v. infusion of 177Lu DOTATATE administered for 20 min via infusion pump with co-infusion of amino-acids solution 1000ml for 1h before and then et least 6h after 177Lu DOTATATE infusion. Therapy consists up to 4 cycles at 8 ± 2 weeks between each other.
90Y DOTATATE and 177Lu DOTATATE (mix each of 50%)Drug
Also called 90Y DOTATATE and 177Lu DOTATATE (mix)
Total activity of 90Y DOTATATE and 177Lu DOTATATE, 4x3.7GBq (14.8 GBq 50% each 90Y and 177Lu). Single session of i.v. infusion of 90Y and 177Lu DOTATATE administered for 20 min via infusion pump with co-infusion of amino-acids solution 1000ml for 1h before and then et least 6h after 177Lu DOTATATE infusion. Therapy consists up to 4 cycles at 8 ± 2 weeks between each other.

Study groups in NCT04029428
Study group	Role	What they receive
90Y DOTATATE	Active comparator	Therapy 90Y DOTATATE, total activity 4x3.7GBq (14.8 GBq), i.v. infusion of 90Y DOTATATE administered for 20 min. via infusion pump with co-infusion of amino-acids (AA) solution 1000ml for 1h before and then et least 6h after 90Y DOTATATE infusion. Therapy consists up to 4 cycles at 8 ± 2 weeks between each other. Receives: Drug: 90Y-DOTATATE
177Lu DOTATATE or mix 90Y and 177Lu DOTATATE (50% each)	Experimental	Therapy 177Lu DOTATATE, total activity 4x5.55GBq (22.2 GBq), i.v. infusion of 177Lu DOTATATE administered for 20 min via infusion pump with co-infusion of amino-acids solution (AA) 1000ml for 1h before and then et least 6h after 177Lu DOTATATE infusion. Therapy consists up to 4 cycles at 8 ± 2 weeks between each other or therapy 90Y and 177Lu DOTATATE, 4x3.7GBq total activity 14.8 GBq, (mix 50% each 90Y and 177Lu), i.v. infusion of mix 90Y and 177Lu DOTATATE administered for 20 min via infusion pump with co-infusion of amino-acids (AA) solution 1000ml for 1h before and then et least 6h after 90Y and 177Lu DOTATATE infusion. Therapy consists up to 4 cycles at 8 ± 2 weeks between each other. Receives: Drug: (177Lu-DOTAOTyr3)Octreotate; Drug: 90Y DOTATATE and 177Lu DOTATATE (mix each of 50%)

What is being measured

The primary outcome is the main question the study is designed to answer.

PFS - Progression Free Survival (time - months)
PFS is the time from the date of the start therapy to the date of first observation of documented disease progression or death due to any cause. Patients without tumor progression at the time of analysis will be censored at their last date of tumor evaluation.
Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
CT or MRI tumour assessment will be used to response evaluation. CT/MRI tumour assessment will be performed before start of PRRT and then after 6+2 weeks after last PRRT session followed by 6 months intervals during first 3 years of follow-up, after that annually. The measurement of PFS will be calculated in months.
Measured: up to 8 years

Secondary outcomes (10)

OS - Overall Survival (time months)
Overall survival is defined as the time from the date of the start therapy to the date of death due to any cause or the date of last contact (censored observation) at the date of data cut-off. The measurement of OS will be calculated in months.
Measured: up to 8 years
Performance Status (PS) - evaluation criteria
Clinical response based on physical performance status (PS) using standard evaluation based on WHO/ECOG criteria. It will be assessed before each treatment cycle and then followed by 6 weeks after completion of therapy and then at three-month intervals. The measurement will be in the scale as follows: 0-asymptomatic, 1=symptomatic but completely ambulatory, 2=Symptomatic <50% in bed during the day, 3= Symptomatic >50% in bed during the day; 4=Bedbound; 5=Death.
Measured: up to 8 years
Cancer Related Symptoms - assessment of clinical criteria
Clinical response based on potential relief in the initial phase before PRRT during and after PRRT. Items will be assessed, including: appetite, malaise, pain associated with the disease, nausea, vomiting, fever, wheezing and abdominal pain or any other symptoms of advanced cancer. All of the above will be assessed as yes / no. Intensity will be recorded in the quality assessment.
It will be evaluated before treatment, before each treatment cycle, and then 6 weeks after the end of therapy, and then at three-month intervals. The measurement will be made in the qualitative data set and categorized as improvement, stabilization or disease progression.
Measured: From date of first enrollment to the end of the follow-up, overall up to 8 years.
Hormonal overproduction symptoms - assessment of clinical criteria
Hormonal response based on relief of symptoms of hormonal overproduction, which will be compare to clinical symptoms before PRRT, during and after PRRT during clinical follow-up. The presence of specific symptoms with hormone overproduction including: 1. Carcinoid syndrome (CS) - initial intensity of diarrhea and potential relief after PRRT (number per day), initial intensity of flushing and potential relief after PRRT (number per day). 2. Presence of heartburn in case of NET with ZES (Zollinger-Elisson syndrome) initial intensity and potential relief during PRRT and after finished PRRT during clinical follow-up. 3. Presence of hypoglycemia in case of NET with insulin overproduction (insulinoma), initial intensity of hypoglycemia before PRRT and potential relief after PRRT during clinical follow-up. The measurement will be made in a set of the qualitative data as improvement, stabilization or disease progression.
Measured: From date of first enrollment to the end of the follow-up, overall up to 8 years.
ORR - Objective Response Rate - evaluation criteria
The evaluation of objective response will be utilized by multiphase structural imaging before and after i.v. contrast enhancement (CT or MRI). The radiological response will be based on RECIST 1.0 using standard terminology of objective response, performed before start of PRRT and then after 6+2 weeks after last PRRT therapy followed by 6 months intervals during first 3 years of follow-up, after that annually. The measurement will be made in a set of quantitative data as partial response (PR), stable disease (SD) or disease progression (DP).
Measured: from date of first enrollment to the end of the follow-up, overall up to 8 years.
Safety Assessments - Laboratory Parameters - evaluation criteria: CTCAEs ver. 4.0
Changes from Baseline in Hematology (WBC, RBC, platelets, haemoglobin), Blood chemistry (BUN, serum creatinine and creatinine clearance, uric acid, albumin, total bilirubin, AP, aspartate aminotransferase [AST/ASAT], alanine aminotransferase [ALT/ALAT], gamma-glutamyl transferase [γ-GT], [Na], [K], lactic dehydrogenase [LDH], glycosylated hemoglobin/hemoglobin A1c [glycoHb] and specific biomarkers Chromogranin-A (CgA) in the serum and 5-Hydroxyindoleacetic acid (5-HIAA) in the urine.
The measurement will be made in a set of quantitative data, based on CTCAEs ver. 4.0. https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf
Measured: from date of first enrollment to the end of the follow-up, overall up to 8 years.
Vital Signs - heart rate - physiological parameter
heart rate (beats per minute)
Measured: from date of first enrollment to the end of the follow-up, overall up to 8 years.
Systolic and diastolic blood pressure - physiological parameter
mmHg.
Measured: from date of first enrollment to the end of the follow-up, overall up to 8 years.
BMI - Body Mass Index - physiological parameter
weight (kg), height (m) Body Mass Index (BMI kg/m2). The measurement will be made in a set of quantitative data.
Measured: from date of first enrollment to the end of the follow-up, overall up to 8 years.
ECG - physiological parameter
ECG analysis during each therapy session and clinical follow-up, including: P Wave, QRS Complex, QT Interval. The measurement will be made in a set of quantitative data.
Measured: from date of first enrollment to the end of the follow-up, overall up to 8 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

2 Nov 20041 Jan 2021

First posted23 Jul 2019
Study start2 Nov 2004
Primary completion1 Jan 2021 (estimated)
Study completion1 Jan 2021 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (11)Papers the sponsor has linked to this study.
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 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Model description: Every patients from groups as follows: Gastro-Entero-Pancreatic Neuroendocrine Tumours - GEP-NET, (G1, G2 and G3), Broncho-pulmonary Carcinoids (BPCs Atypical-AC or Typical-TC), pheochromocytoma/paragangliomas (PPGLs) and neuroendocrine tumours of unknown primary (NET-CUP).
Masking: None (open label)
Enrolment: 150 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04029428
Sponsor's protocol ID: POLNETS_2004
Acronym: POLNETS_PRRT
Status last verified: Mar 2020
First submitted: 19 May 2019
Last updated: 1 Apr 2020
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Caplin ME, Buscombe JR, Hilson AJ, Jones AL, Watkinson AF, Burroughs AK. Carcinoid tumour. Lancet. 1998 Sep 5;352(9130):799-805. doi: 10.1016/S0140-6736(98)02286-7.
PubMed 9737302
Waldherr C, Pless M, Maecke HR, Haldemann A, Mueller-Brand J. The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study. Ann Oncol. 2001 Jul;12(7):941-5. doi: 10.1023/a:1011160913619.
PubMed 11521799
Paganelli G, Zoboli S, Cremonesi M, Bodei L, Ferrari M, Grana C, Bartolomei M, Orsi F, De Cicco C, Macke HR, Chinol M, de Braud F. Receptor-mediated radiotherapy with 90Y-DOTA-D-Phe1-Tyr3-octreotide. Eur J Nucl Med. 2001 Apr;28(4):426-34. doi: 10.1007/s002590100490.
PubMed 11357492
Reubi JC, Schar JC, Waser B, Wenger S, Heppeler A, Schmitt JS, Macke HR. Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med. 2000 Mar;27(3):273-82. doi: 10.1007/s002590050034.
PubMed 10774879
Kwekkeboom DJ, Bakker WH, Kam BL, Teunissen JJ, Kooij PP, de Herder WW, Feelders RA, van Eijck CH, de Jong M, Srinivasan A, Erion JL, Krenning EP. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA(0),Tyr3]octreotate. Eur J Nucl Med Mol Imaging. 2003 Mar;30(3):417-22. doi: 10.1007/s00259-002-1050-8. Epub 2003 Jan 9.
PubMed 12634971
Esser JP, Krenning EP, Teunissen JJ, Kooij PP, van Gameren AL, Bakker WH, Kwekkeboom DJ. Comparison of [(177)Lu-DOTA(0),Tyr(3)]octreotate and [(177)Lu-DOTA(0),Tyr(3)]octreotide: which peptide is preferable for PRRT? Eur J Nucl Med Mol Imaging. 2006 Nov;33(11):1346-51. doi: 10.1007/s00259-006-0172-9. Epub 2006 Jul 18.
PubMed 16847654
Waldherr C, Pless M, Maecke HR, Schumacher T, Crazzolara A, Nitzsche EU, Haldemann A, Mueller-Brand J. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. J Nucl Med. 2002 May;43(5):610-6.
PubMed 11994522
Cwikla JB, Sankowski A, Seklecka N, Buscombe JR, Nasierowska-Guttmejer A, Jeziorski KG, Mikolajczak R, Pawlak D, Stepien K, Walecki J. Efficacy of radionuclide treatment DOTATATE Y-90 in patients with progressive metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs): a phase II study. Ann Oncol. 2010 Apr;21(4):787-794. doi: 10.1093/annonc/mdp372. Epub 2009 Oct 15.
PubMed 19833821
Chinol M, Bodei L, Cremonesi M, Paganelli G. Receptor-mediated radiotherapy with Y-DOTA-DPhe-Tyr-octreotide: the experience of the European Institute of Oncology Group. Semin Nucl Med. 2002 Apr;32(2):141-7. doi: 10.1053/snuc.2002.31563.
PubMed 11965609
Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, Feelders RA, van Aken MO, Krenning EP. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008 May 1;26(13):2124-30. doi: 10.1200/JCO.2007.15.2553.
PubMed 18445841
Bushnell DL Jr, O'Dorisio TM, O'Dorisio MS, Menda Y, Hicks RJ, Van Cutsem E, Baulieu JL, Borson-Chazot F, Anthony L, Benson AB, Oberg K, Grossman AB, Connolly M, Bouterfa H, Li Y, Kacena KA, LaFrance N, Pauwels SA. 90Y-edotreotide for metastatic carcinoid refractory to octreotide. J Clin Oncol. 2010 Apr 1;28(10):1652-9. doi: 10.1200/JCO.2009.22.8585. Epub 2010 Mar 1.
PubMed 20194865

Want to know more?

Jarosław B Ćwikła, MD, PhD

+48602112599

jbcwikla@interia.pl

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 1 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Clinical Study of the Use of Yttrium-90 (90Y) and/or Lutecium-177 (177Lu) DOTATATE (DOTA-0-Tyr3-Octreotate) in the Treatment of Disseminated and / or Symptomatic Tumors With Somatostatin Receptor Overexpression
ClinicalTrials.gov ID: NCT04029428
Acronym / sponsor ID: POLNETS_PRRT / POLNETS_2004
Conditions: Neuroendocrine Tumors
Keywords: PRRT - Peptide Receptor Radionuclide Therapy,, GEP-NET - Gastro-Entero-Pancreatic Neuroendocrine Tumours;, BPCs - Bronchopulmonary Carcinoids (Atypical & Typical), PPGLs - Pheochromocytomas/Paragangliomas;, NET-CUP - Neuroendocrine Tumours of unknown primary, clinical efficacy, toxcity - adverse events (AEs), OS - overall survival
Phase: Phase 2
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 150 participants (estimated)
Lead sponsor: University of Warmia and MazuryUniversity, hospital or other
Collaborators: Stowarzyszenie Pacjentów i Osób Wspierających Chorych na Guzy Neuroendokrynne
Study start: 2 Nov 2004 (actual)
Primary completion: 1 Jan 2021 (estimated)
Study completion: 1 Jan 2021 (estimated)
First posted: 23 Jul 2019 (actual)
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.

Detailed description

Total activity of 90Y DOTATATE 4x3,7GBq (14,8 GBq) for 4 cycles at 8 ± 2 weeks (400mCi)
Total activity of 177Lu DOTATATE 4x5,55GBq (22,2 GBq for 4 cycles at 8 ± 2 weeks (600 mCi)
Total activity of mix both 90Y DOTATATE and 177Lu DOTATATE (50 each) 4x3,7 GBq for 4 cycles at 8 ± 2 weeks (400mCi).

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: Every patients from groups as follows: Gastro-Entero-Pancreatic Neuroendocrine Tumours - GEP-NET, (G1, G2 and G3), Broncho-pulmonary Carcinoids (BPCs Atypical-AC or Typical-TC), pheochromocytoma/paragangliomas (PPGLs) and neuroendocrine tumours of unknown primary (NET-CUP).

Arm	Type	Receives
90Y DOTATATE	Active comparator	Drug: 90Y-DOTATATETherapy 90Y DOTATATE, total activity 4x3.7GBq (14.8 GBq), i.v. infusion of 90Y DOTATATE administered for 20 min. via infusion pump with co-infusion of amino-acids (AA) solution 1000ml for 1h before and then et least 6h after 90Y DOTATATE infusion. Therapy consists up to 4 cycles at 8 ± 2 weeks between each other.
177Lu DOTATATE or mix 90Y and 177Lu DOTATATE (50% each)	Experimental	Drug: (177Lu-DOTAOTyr3)Octreotate, Drug: 90Y DOTATATE and 177Lu DOTATATE (mix each of 50%)Therapy 177Lu DOTATATE, total activity 4x5.55GBq (22.2 GBq), i.v. infusion of 177Lu DOTATATE administered for 20 min via infusion pump with co-infusion of amino-acids solution (AA) 1000ml for 1h before and then et least 6h after 177Lu DOTATATE infusion. Therapy consists up to 4 cycles at 8 ± 2 weeks between each other or therapy 90Y and 177Lu DOTATATE, 4x3.7GBq total activity 14.8 GBq, (mix 50% each 90Y and 177Lu), i.v. infusion of mix 90Y and 177Lu DOTATATE administered for 20 min via infusion pump with co-infusion of amino-acids (AA) solution 1000ml for 1h before and then et least 6h after 90Y and 177Lu DOTATATE infusion. Therapy consists up to 4 cycles at 8 ± 2 weeks between each other.

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

Adults ≥18 years old, male or female, with histologically proven, well-differentiated G1/2 GEP-NET, BPCs, PPGLs or NET (cancer with unknown primary - CUP), with Ki-67 <20%, in selected cases patients with NETG3 will be included if there will be reported well/moderate morphological appearance but Ki-67>20% but less then Ki<30%; and there will be high expression of somatostatin receptor seen in functional imaging utilized functional imaging 99mTc HYNICTOC or 68Ga DOTATATE or 68Ga DOTATOC.
The presence of high expression of somatostatin receptors demonstrated on Somatostatin Receptor Imaging using 99mTc HYNICTOC (SPECT) or 68Ga DOTATATE or 68Ga DOTATOC (PET) scans, et least as uptake in not involved liver, Krenning >2
Non-resectable, advanced determined by an appropriately specialized surgeon or deemed not suitable for liver directed therapies where liver is the only site of disease;
Performance status (PS) based on ECOG 0-2;
Unresectable, advanced/metastatic progressive disease evaluated as clinical, biochemical, bad control symptoms of tumour hypersecretion or disease progression seen in imaging structural or functional.

Key exclusion criteria (17 listed)

• Primary non-NETs;

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
90Y-DOTATATEAlso: 90Y DOTATATETotal activity of 90Y DOTATATE, 4x3.7GBq (14.8 GBq). Single session of i.v. infusion of 90Y DOTATATE administered for 20 min via infusion pump with co-infusion of amino-acids solution 1000ml for 1h before and then et least 6h after 90Y DOTATATE infusion. Therapy consists up to 4 cycles at 8 ± 2 weeks between each other.	Drug	90Y DOTATATE
(177Lu-DOTAOTyr3)OctreotateAlso: 177Lu DOTATATETotal activity of 177Lu DOTATATE, 4x5.55GBq (22.2 GBq). Single session of i.v. infusion of 177Lu DOTATATE administered for 20 min via infusion pump with co-infusion of amino-acids solution 1000ml for 1h before and then et least 6h after 177Lu DOTATATE infusion. Therapy consists up to 4 cycles at 8 ± 2 weeks between each other.	Drug	177Lu DOTATATE or mix 90Y and 177Lu DOTATATE (50% each)
90Y DOTATATE and 177Lu DOTATATE (mix each of 50%)Also: 90Y DOTATATE and 177Lu DOTATATE (mix)Total activity of 90Y DOTATATE and 177Lu DOTATATE, 4x3.7GBq (14.8 GBq 50% each 90Y and 177Lu). Single session of i.v. infusion of 90Y and 177Lu DOTATATE administered for 20 min via infusion pump with co-infusion of amino-acids solution 1000ml for 1h before and then et least 6h after 177Lu DOTATATE infusion. Therapy consists up to 4 cycles at 8 ± 2 weeks between each other.	Drug	177Lu DOTATATE or mix 90Y and 177Lu DOTATATE (50% each)

Primary outcome

PFS - Progression Free Survival (time - months)
Time frame: up to 8 years
PFS is the time from the date of the start therapy to the date of first observation of documented disease progression or death due to any cause. Patients without tumor progression at the time of analysis will be censored at their last date of tumor evaluation. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. CT or MRI tumour assessment will be used to response evaluation. CT/MRI tumour assessment will be performed before start of PRRT and then after 6+2 weeks after last PRRT session followed by 6 months intervals during first 3 years of follow-up, after that annually. The measurement of PFS will be calculated in months.

10 secondary outcomes

OS - Overall Survival (time months)
Time frame: up to 8 years
Performance Status (PS) - evaluation criteria
Time frame: up to 8 years
Cancer Related Symptoms - assessment of clinical criteria
Time frame: From date of first enrollment to the end of the follow-up, overall up to 8 years.
Hormonal overproduction symptoms - assessment of clinical criteria
Time frame: From date of first enrollment to the end of the follow-up, overall up to 8 years.
ORR - Objective Response Rate - evaluation criteria
Time frame: from date of first enrollment to the end of the follow-up, overall up to 8 years.
Safety Assessments - Laboratory Parameters - evaluation criteria: CTCAEs ver. 4.0
Time frame: from date of first enrollment to the end of the follow-up, overall up to 8 years.
Vital Signs - heart rate - physiological parameter
Time frame: from date of first enrollment to the end of the follow-up, overall up to 8 years.
Systolic and diastolic blood pressure - physiological parameter
Time frame: from date of first enrollment to the end of the follow-up, overall up to 8 years.
BMI - Body Mass Index - physiological parameter
Time frame: from date of first enrollment to the end of the follow-up, overall up to 8 years.
ECG - physiological parameter
Time frame: from date of first enrollment to the end of the follow-up, overall up to 8 years.

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2020.
Background: PubMed 9737302Caplin ME, Buscombe JR, Hilson AJ, Jones AL, Watkinson AF, Burroughs AK. Carcinoid tumour. Lancet. 1998 Sep 5;352(9130):799-805. doi: 10.1016/S0140-6736(98)02286-7.
Background: PubMed 11521799Waldherr C, Pless M, Maecke HR, Haldemann A, Mueller-Brand J. The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study. Ann Oncol. 2001 Jul;12(7):941-5. doi: 10.1023/a:1011160913619.
Background: PubMed 11357492Paganelli G, Zoboli S, Cremonesi M, Bodei L, Ferrari M, Grana C, Bartolomei M, Orsi F, De Cicco C, Macke HR, Chinol M, de Braud F. Receptor-mediated radiotherapy with 90Y-DOTA-D-Phe1-Tyr3-octreotide. Eur J Nucl Med. 2001 Apr;28(4):426-34. doi: 10.1007/s002590100490.
Background: PubMed 10774879Reubi JC, Schar JC, Waser B, Wenger S, Heppeler A, Schmitt JS, Macke HR. Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med. 2000 Mar;27(3):273-82. doi: 10.1007/s002590050034.
Background: PubMed 12634971Kwekkeboom DJ, Bakker WH, Kam BL, Teunissen JJ, Kooij PP, de Herder WW, Feelders RA, van Eijck CH, de Jong M, Srinivasan A, Erion JL, Krenning EP. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA(0),Tyr3]octreotate. Eur J Nucl Med Mol Imaging. 2003 Mar;30(3):417-22. doi: 10.1007/s00259-002-1050-8. Epub 2003 Jan 9.
Background: PubMed 16847654Esser JP, Krenning EP, Teunissen JJ, Kooij PP, van Gameren AL, Bakker WH, Kwekkeboom DJ. Comparison of [(177)Lu-DOTA(0),Tyr(3)]octreotate and [(177)Lu-DOTA(0),Tyr(3)]octreotide: which peptide is preferable for PRRT? Eur J Nucl Med Mol Imaging. 2006 Nov;33(11):1346-51. doi: 10.1007/s00259-006-0172-9. Epub 2006 Jul 18.
Background: PubMed 11994522Waldherr C, Pless M, Maecke HR, Schumacher T, Crazzolara A, Nitzsche EU, Haldemann A, Mueller-Brand J. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. J Nucl Med. 2002 May;43(5):610-6.
Background: PubMed 19833821Cwikla JB, Sankowski A, Seklecka N, Buscombe JR, Nasierowska-Guttmejer A, Jeziorski KG, Mikolajczak R, Pawlak D, Stepien K, Walecki J. Efficacy of radionuclide treatment DOTATATE Y-90 in patients with progressive metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs): a phase II study. Ann Oncol. 2010 Apr;21(4):787-794. doi: 10.1093/annonc/mdp372. Epub 2009 Oct 15.
Background: PubMed 11965609Chinol M, Bodei L, Cremonesi M, Paganelli G. Receptor-mediated radiotherapy with Y-DOTA-DPhe-Tyr-octreotide: the experience of the European Institute of Oncology Group. Semin Nucl Med. 2002 Apr;32(2):141-7. doi: 10.1053/snuc.2002.31563.
Background: PubMed 18445841Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, Feelders RA, van Aken MO, Krenning EP. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008 May 1;26(13):2124-30. doi: 10.1200/JCO.2007.15.2553.
Background: PubMed 20194865Bushnell DL Jr, O'Dorisio TM, O'Dorisio MS, Menda Y, Hicks RJ, Van Cutsem E, Baulieu JL, Borson-Chazot F, Anthony L, Benson AB, Oberg K, Grossman AB, Connolly M, Bouterfa H, Li Y, Kacena KA, LaFrance N, Pauwels SA. 90Y-edotreotide for metastatic carcinoid refractory to octreotide. J Clin Oncol. 2010 Apr 1;28(10):1652-9. doi: 10.1200/JCO.2009.22.8585. Epub 2010 Mar 1.
Individual participant dataSharing planned: No

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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.

Jarosław B Ćwikła, MD, PhD contact

+48602112599

jbcwikla@interia.pl

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 14 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 1 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Poland. 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 phase mean?

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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Jarosław B Ćwikła, MD, PhD (+48602112599, jbcwikla@interia.pl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PFS - Progression Free Survival (time - months) (time frame: up to 8 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04029428, which also lists 11 linked publications.

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 1 Apr 2020.