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

NCT04029428 | Unknown Phase 2

• 1 other identifier: POLNETS_2004
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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).

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; PFS - progression free survival

Outcome Measures

Primary Outcomes (1)

• 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.

  up to 8 years

Secondary Outcomes (10)

• OS - Overall Survival (time months)

  up to 8 years

• Performance Status (PS) - evaluation criteria

  up to 8 years

• Cancer Related Symptoms - assessment of clinical criteria

  From date of first enrollment to the end of the follow-up, overall up to 8 years.

• Hormonal overproduction symptoms - assessment of clinical criteria

  From date of first enrollment to the end of the follow-up, overall up to 8 years.

• ORR - Objective Response Rate - evaluation criteria

  from date of first enrollment to the end of the follow-up, overall up to 8 years.

Study Arms (2)

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.

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.

Drug: (177Lu-DOTAOTyr3)Octreotate; Drug: 90Y DOTATATE and 177Lu DOTATATE (mix each of 50%)

Interventions

90Y-DOTATATE DRUG

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.

Also known as: 90Y DOTATATE

90Y DOTATATE

(177Lu-DOTAOTyr3)Octreotate DRUG

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.

Also known as: 177Lu DOTATATE

177Lu DOTATATE or mix 90Y and 177Lu DOTATATE (50% each)

90Y DOTATATE and 177Lu DOTATATE (mix each of 50%) DRUG

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.

Also known as: 90Y DOTATATE and 177Lu DOTATATE (mix)

177Lu DOTATATE or mix 90Y and 177Lu DOTATATE (50% each)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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),
• 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.
• Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments;
• Signed, written informed consent.

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• University of Warmia and Mazury: lead
• Stowarzyszenie Pacjentów i Osób Wspierających Chorych na Guzy Neuroendokrynne: collaborator

Study Sites (1)

Centrum Diagnostyczno-Lecznicze Gammed

Warsaw, 02-351, Poland

RECRUITING

Related Publications (11)

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  PMID: 9737302 BACKGROUND

• 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.

  PMID: 11521799 BACKGROUND

• 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.

  PMID: 11357492 BACKGROUND

• 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.

  PMID: 10774879 BACKGROUND

• 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.

  PMID: 12634971 BACKGROUND

• 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.

  PMID: 16847654 BACKGROUND

• 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.

  PMID: 11994522 BACKGROUND

• 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.

  PMID: 19833821 BACKGROUND

• 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.

  PMID: 11965609 BACKGROUND

• 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.

  PMID: 18445841 BACKGROUND

• 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.

  PMID: 20194865 BACKGROUND

MeSH Terms

Conditions

Neuroendocrine Tumors; Paraganglioma

Interventions

90Y-octreotate, DOTA(0)-Tyr(3)-Thr(8)-; lutetium Lu 177 dotatate

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Jarosław B Ćwikła, MD, PhD

CONTACT

+48602112599; jbcwikla@interia.pl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Clinical Professor; Head of Nuclear Medicine; Principal Investigator

Model Details: 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).

Study Record Dates

• First Submitted: May 19, 2019
• First Posted: July 23, 2019
• Study Start: November 2, 2004
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2021
• Last Updated: April 1, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)