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Neuroendocrine TumorsFENET-2016NCT04790708

Peptide Receptor Radionuclide Therapy (PRRT) in Tumors With High Expression of Somatostatin Receptors (Phase 2)

A study testing Lutetium-177 (177Lu)-DOTATOC, Yttrium-90 (90Y)-DOTATOC and 177Lu-DOTATOC + 90Y-DOTATOC in people with Neuroendocrine Tumors and Peptide Receptor Radionuclide Therapy (PRRT), run by University Hospital of Ferrara at 1 site in Italy.

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 The sponsor has not verified this record for over two years, so it may be out of date.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

The rationale behind the purpose of this study lays on: the evidence that PRRT could represent a valuable treatment for the majority of patients with neuroendocrine tumor (NET) in disease progression, operated or inoperable, presenting lesions expressing somatostatin receptors and for which standard treatments are not… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Lutetium-177 (177Lu)-DOTATOC, Yttrium-90 (90Y)-DOTATOC and 177Lu-DOTATOC + 90Y-DOTATOC
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
250 participants
Where
1 siteItaly
Study dates
2 Jul 2018to 30 Jun 2023
Phase
Interventional
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1. Age ≥18 years, of both sexes, of any ethnicity;
  • 2. Cyto-histological and immunohistochemical diagnosis of NET;
  • 3. Evaluation of the cell proliferation index by studying Ki-67 and / or E3 ubiquitin-protein ligase (MIB-1).
  • 4. Illness measurable according to RECIST 1.1 criteria by imaging conventional (CT with contrast medium or MRI with contrast medium) not earlier than two months with respect to enrollment;
  • 5. Elevated expression of somatostatin receptors documented by PET-CT with 68Ga-DOTATOC in the target lesion (s). It is defined as "high expression of somatostatin receptors "a ratio of Maximum standardized uptake value (SUVmax) lesion / Mean standardized uptake value (SUVmean) muscle ≥ 4: 1 calculated with semi-quantitative analysis on examination PET-CT with 68Ga-DOTATOC;
  • 6. Dosage of Chromogranin A (and any other specific markers) not prior to two months of enrollment;
Show all 14Show fewer
  • 7. Evaluation of glucose metabolism in the target lesion (s) by PET-CT with 18F-FDG;
  • 8. Preserved haematological, hepatic and renal parameters, in particular: white blood cells ≥2500 / μL; platelets ≥ 90000 / μL; hemoglobin ≥ 9 gr / dL; creatinine ≤ 2 mg / dL; bilirubin ≤ 2.5 mg / dL
  • 9. Eastern Cooperative Oncology Group (ECOG) performance status ≤2;
  • 10. Life expectancy ≥ 6 months;
  • 11. Stable or progressive disease, at any stage, both in operated patients that inoperable;
  • 12. Absence of standard treatments already documented and of equal effectiveness;
  • 13. Absence of surgical, chemotherapy and / or radiotherapy treatments for at least 30 days. On the other hand, patients in therapy with somatostatin analogues or biologics, such as mechanistic target of rapamycin (m-TOR) inhibitors;
  • 14. Voluntary participation in the study by signing the consent form informed, after reading and complete understanding of the information notes.

Who cannot join

  • 1. Lack of the requirements listed above;
  • 2. State of pregnancy;
  • 3. Breastfeeding and relative refusal to suspend breastfeeding;
  • 4. Participation in another therapeutic experimental clinical protocol in the four weeks prior to the PRRT;
  • 5. Bone marrow invasion of disease> 25% confirmed;
  • 6. Previous extensive radiotherapy treatments.

Trial locations and contacts

1 site in 1 country.

Mirco Bartolomei, MD contact

0532236082

m.bartolomei@ospfe.it

Licia Uccelli, PhD contact

0532237462

licia.uccelli@unife.it

Italy1 site, 1 recruiting

  • University Hospital of Ferrara

    Ferrara, 44124

    Mirco Bartolomei, MD, 0532-236082, m.bartolomei@ospfe.it

    0532-236387, medicina.nucleare@ospfe.it

    Recruiting

Other trials in Italy

About this study

Official title: Peptide Receptor Radionuclide Therapy (PRRT) in Tumors With High Expression of Somatostatin Receptors

The rationale behind the purpose of this study lays on:

  • the evidence that PRRT could represent a valuable treatment for the majority of patients with neuroendocrine tumor (NET) in disease progression, operated or inoperable, presenting lesions expressing somatostatin receptors and for which standard treatments are not already available;
  • the current impossibility of acquiring on the market radiolabelled analogues of somatostatin used for PRRT with marketing authorisation;
  • the need to collect a larger case history than in previous studies;
  • the need to stratify the various histotypes based on the response obtained;
  • the need to define new treatment schemes that guarantee the maximum efficacy and the lowest possible toxicity - with low cumulative (and per cycle) activities radiopharmaceutical and according to the concept of dose hyperfractionation - with a view to an optimal balance between risk and benefit.
Being tested
Lutetium-177 (177Lu)-DOTATOC, Yttrium-90 (90Y)-DOTATOC, 177Lu-DOTATOC + 90Y-DOTATOC, Re-treatment 177Lu-DOTATOC, Re-treatment 90Y-DOTATOC
Keywords
Neuroendocrine Tumors, 90Y, 177Lu, PRRT
Medical subject headings
Neuroendocrine Tumors

What participants receive

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

  • Lutetium-177 (177Lu)-DOTATOCRadiation

    Also called "MONO"

    5 cycles of 3,7 e 5,55 gigabequerel (GBq) of 177Lu-DOTATOC every 8-10 weeks. Cumulative activity: 18,5 e 27,75 GBq

  • Yttrium-90 (90Y)-DOTATOCRadiation

    5 cycles of 1,85 e 2,775 GBq of 90Y-DOTATOC every 8-10 weeks. Cumulative activity: 9,25 e 13,875 GBq

  • 177Lu-DOTATOC + 90Y-DOTATOCRadiation

    Also called "DUO"

    3 cycles of 3,7 e 5,55 GBq of 177Lu-DOTATOC alternated with 2 cycles of 1,85 e 2,775 GBq of 90Y-DOTATOC every 8-10 weeks.

    Cumulative activity: 18,5 e 27,75 GBq of 177Lu-DOTATOC and 9,25 e 13,875 GBq of 90Y-DOTATOC

  • Re-treatment 177Lu-DOTATOCRadiation

    3 cycles of 3,7 e 5,55 GBq of 177Lu-DOTATOC every 8-10weeks. Cumulative activity: 11,1 e 16,65 GBq of 177Lu-DOTATOC

  • Re-treatment 90Y-DOTATOCRadiation

    3 cycles of 1,85 e 2,775 GBq of 90Y-DOTATOC every 8-10 weeks Cumulative activity: 5,55 e 8,325 GBq of 90Y-DOTATOC

Study groups in NCT04790708
Study groupRoleWhat they receive
Midgut NETsExperimental75 patients affected by non-functional and functional NETs arising from: stomach, duodenum, jejunum, ileum, colon and rectum.
Receives: Radiation: Lutetium-177 (177Lu)-DOTATOC; Radiation: Yttrium-90 (90Y)-DOTATOC; Radiation: 177Lu-DOTATOC + 90Y-DOTATOC; Radiation: Re-treatment 177Lu-DOTATOC; Radiation: Re-treatment 90Y-DOTATOC
Pancreatic NETsExperimental75 patients affected by non-functional and functional NETs arising from Pancreas.
Receives: Radiation: Lutetium-177 (177Lu)-DOTATOC; Radiation: Yttrium-90 (90Y)-DOTATOC; Radiation: 177Lu-DOTATOC + 90Y-DOTATOC; Radiation: Re-treatment 177Lu-DOTATOC; Radiation: Re-treatment 90Y-DOTATOC
Bronchial NETsExperimental25 patients affected by non-functional and functional Bronchial NETs.
Receives: Radiation: Lutetium-177 (177Lu)-DOTATOC; Radiation: Yttrium-90 (90Y)-DOTATOC; Radiation: 177Lu-DOTATOC + 90Y-DOTATOC; Radiation: Re-treatment 177Lu-DOTATOC; Radiation: Re-treatment 90Y-DOTATOC
Sympathetic-Adrenergic axis NEtsExperimental25 patients affected by non-functional and functional: Pheochromocytoma, Paraganglioma and Neuroblastoma
Receives: Radiation: Lutetium-177 (177Lu)-DOTATOC; Radiation: Yttrium-90 (90Y)-DOTATOC; Radiation: 177Lu-DOTATOC + 90Y-DOTATOC; Radiation: Re-treatment 177Lu-DOTATOC; Radiation: Re-treatment 90Y-DOTATOC
Other NetsExperimental25 patients affected by non-functional and functional NETs arising from Skin, Thyroid (medullary thyroid and anaplastic cancer) and Parathyroids.
Receives: Radiation: Lutetium-177 (177Lu)-DOTATOC; Radiation: Yttrium-90 (90Y)-DOTATOC; Radiation: 177Lu-DOTATOC + 90Y-DOTATOC; Radiation: Re-treatment 177Lu-DOTATOC; Radiation: Re-treatment 90Y-DOTATOC
Cancers of Unknown Primary Origin (CUP) NETsExperimental25 patients affected by non-functional and functional unknown primary NETs
Receives: Radiation: Lutetium-177 (177Lu)-DOTATOC; Radiation: Yttrium-90 (90Y)-DOTATOC; Radiation: 177Lu-DOTATOC + 90Y-DOTATOC; Radiation: Re-treatment 177Lu-DOTATOC; Radiation: Re-treatment 90Y-DOTATOC

What is being measured

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

  1. Disease Control Rate

    Post-treatment evaluation will be performed with:

    • a clinical examination;
    • a comparative morphological re-evaluation, using version 1.1 of Response evaluation criteria in solid tumors (RECIST criteria) on Computed Tomography (CT);
    • a comparative functional re-evaluation, performed both on 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission computed tomography (PET/CT) and Gallium-68 (68Ga)-DOTATOC PET/CT using visual and semi-quantitative parameters (such as SUVmax).

    Based on all these parameters, Disease Control Rate will be labelled as: Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression Disease (PD).

    Measured: 12 months

Secondary outcomes (4)

  1. Progression Free Survival

    Progression free survival is defined as the time intercurrent from treatment start to the date of first observation of documented disease progression or death due to any cause.

    Measured: 6 months

  2. Overall Survival

    Overall survival is defined as the time intercurrent from treatment start to the date of death due to any cause, or the date of last contact.

    Measured: 6 months

  3. Evaluation of PRRT Safety

    The evaluation of Treatment-Emergent Adverse Events, defined as any G3/G4 toxicity. The evaluation will be performed during every treatment cycle and after 12, 18, 24, 30, 36 and 42 months after the last treatment cycle and will be based on version 4.0 of Common Terminology Criteria for Adverse Events (CTC-AE) toxicity criteria.

    Measured: 6 months

  4. Evaluation of Quality of Life

    Quality of Life (QoL) will be evaluated with quality of life questionnaire, version 3 (QLQ-C30) by European Organisation for Research and Treatment of Cancer (EORTC). The questionnaire includes five functional scales, three symptom scales, a global health status / QoL scale, and six single items.

    All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

    Measured: 6 months

Timeline

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

  1. First posted10 Mar 2021
  2. Study start2 Jul 2018
  3. Primary completion30 Jun 2023 (estimated)
  4. Study completion30 Jun 2023 (estimated)

Resources

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 N/A
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
250 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04790708
Sponsor's protocol ID
160990
Other IDs
2016-005129-35, 2016
Acronym
FENET-2016
Status last verified
Mar 2021
First submitted
2 Mar 2021
Last updated
10 Mar 2021
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Smit Duijzentkunst DA, Kwekkeboom DJ, Bodei L. Somatostatin Receptor 2-Targeting Compounds. J Nucl Med. 2017 Sep;58(Suppl 2):54S-60S. doi: 10.2967/jnumed.117.191015.

    PubMed 28864613

  • Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003 Feb 15;97(4):934-59. doi: 10.1002/cncr.11105.

    PubMed 12569593

  • Teunissen JJ, Kwekkeboom DJ, Valkema R, Krenning EP. Nuclear medicine techniques for the imaging and treatment of neuroendocrine tumours. Endocr Relat Cancer. 2011 Oct 17;18 Suppl 1:S27-51. doi: 10.1530/ERC-10-0282. Print 2011 Oct.

    PubMed 22005114

  • Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A, Evans DB. One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008 Jun 20;26(18):3063-72. doi: 10.1200/JCO.2007.15.4377.

    PubMed 18565894

  • Hemminki K, Li X. Incidence trends and risk factors of carcinoid tumors: a nationwide epidemiologic study from Sweden. Cancer. 2001 Oct 15;92(8):2204-10. doi: 10.1002/1097-0142(20011015)92:83.0.co;2-r.

    PubMed 11596039

  • Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker RV, Caplin M, Delle Fave G, Kaltsas GA, Krenning EP, Moss SF, Nilsson O, Rindi G, Salazar R, Ruszniewski P, Sundin A. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008 Jan;9(1):61-72. doi: 10.1016/S1470-2045(07)70410-2.

    PubMed 18177818

  • Kloppel G, Couvelard A, Perren A, Komminoth P, McNicol AM, Nilsson O, Scarpa A, Scoazec JY, Wiedenmann B, Papotti M, Rindi G, Plockinger U; Mallorca Consensus Conference participants; European Neuroendocrine Tumor Society. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: towards a standardized approach to the diagnosis of gastroenteropancreatic neuroendocrine tumors and their prognostic stratification. Neuroendocrinology. 2009;90(2):162-6. doi: 10.1159/000182196. Epub 2009 Aug 28. No abstract available.

    PubMed 19060454

  • Rindi G, Kloppel G, Couvelard A, Komminoth P, Korner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2007 Oct;451(4):757-62. doi: 10.1007/s00428-007-0452-1. Epub 2007 Aug 3.

    PubMed 17674042

  • Scoazec JY, Couvelard A; pour le reseau TENpath (reseau national d'expertise pour le diagnostic anatomopathologique des tumeurs neuroendocrines malignes de l'adulte, sporadiques et familiales). [The new WHO classification of digestive neuroendocrine tumors]. Ann Pathol. 2011 Apr;31(2):88-92. doi: 10.1016/j.annpat.2011.01.001. Epub 2011 Mar 26. French.

    PubMed 21601112

  • Volante M, Gatti G, Papotti M. Classification of lung neuroendocrine tumors: lights and shadows. Endocrine. 2015 Nov;50(2):315-9. doi: 10.1007/s12020-015-0578-x. Epub 2015 Mar 21.

    PubMed 25795289

  • Warner RR. Enteroendocrine tumors other than carcinoid: a review of clinically significant advances. Gastroenterology. 2005 May;128(6):1668-84. doi: 10.1053/j.gastro.2005.03.078.

    PubMed 15887158

  • Massironi S, Sciola V, Peracchi M, Ciafardini C, Spampatti MP, Conte D. Neuroendocrine tumors of the gastro-entero-pancreatic system. World J Gastroenterol. 2008 Sep 21;14(35):5377-84. doi: 10.3748/wjg.14.5377.

    PubMed 18803349

  • Ramage JK, Davies AH, Ardill J, Bax N, Caplin M, Grossman A, Hawkins R, McNicol AM, Reed N, Sutton R, Thakker R, Aylwin S, Breen D, Britton K, Buchanan K, Corrie P, Gillams A, Lewington V, McCance D, Meeran K, Watkinson A; UKNETwork for Neuroendocrine Tumours. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut. 2005 Jun;54 Suppl 4(Suppl 4):iv1-16. doi: 10.1136/gut.2004.053314. No abstract available.

    PubMed 15888809

  • de Baere T, Deschamps F, Tselikas L, Ducreux M, Planchard D, Pearson E, Berdelou A, Leboulleux S, Elias D, Baudin E. GEP-NETS update: Interventional radiology: role in the treatment of liver metastases from GEP-NETs. Eur J Endocrinol. 2015 Apr;172(4):R151-66. doi: 10.1530/EJE-14-0630. Epub 2014 Nov 10.

    PubMed 25385817

  • Jann H, Denecke T, Koch M, Pape UF, Wiedenmann B, Pavel M. Impact of octreotide long-acting release on tumour growth control as a first-line treatment in neuroendocrine tumours of pancreatic origin. Neuroendocrinology. 2013;98(2):137-43. doi: 10.1159/000353785. Epub 2013 Aug 13.

    PubMed 23797176

Questions about this trial

What is this clinical trial studying?

A study testing Lutetium-177 (177Lu)-DOTATOC, Yttrium-90 (90Y)-DOTATOC and 177Lu-DOTATOC + 90Y-DOTATOC in people with Neuroendocrine Tumors and Peptide Receptor Radionuclide Therapy (PRRT), run by University Hospital of Ferrara at 1 site in Italy.

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 6 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 10 Mar 2021. 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 Italy. 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.

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 Mirco Bartolomei, MD (0532236082, m.bartolomei@ospfe.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Control Rate (time frame: 12 months). 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 NCT04790708, which also lists 91 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 10 Mar 2021.

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