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Neuroendocrine TumorsPhase 2MIBNETNCT04831567

Study of MIBG-I131 in Patients With Well Differentiated Neuroendocrine Tumors

A Phase 2 study testing MIBG-I131 in people with Neuroendocrine Tumors, run by AC Camargo Cancer Center at 1 site in Brazil.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is a single-arm, unicentric, single-stage, phase 2 clinical study of therapeutic metaiodobenzylguanidine (MIBG) for patients with metastatic well-differentiated neuroendocrine tumors and radiological progression or intolerance after standard lines of treatment and with MIBG positive scan. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neuroendocrine Tumors
What is being tested?
MIBG-I131
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteBrazil
Study dates
4 Feb 2021to 13 May 2022
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age greater than or equal to 18 years
  • Histological diagnosis of well-differentiated neuroendocrine tumor (NET) (typical and atypical lung carcinoids and NET of all gastroenteropancreatic sites according to World Health Organization (WHO) 2019 classification); metastatic/unresectable, with no possibility of curative treatment.
  • MIBG-I131 positive scan in at least one lesion with uptake compatible with therapeutic effectiveness.
  • Disease with radiological progression (at least 10 percent tumor volume growth) in the last 12 months before day 1 cycle 1.
  • Intolerance due to toxicities or lack of access to standard treatments - [private context (somatostatin analog, everolimus) and public health system (somatostatin analog)].
  • Measurable disease
Show all 15Show fewer
  • Eastern Cooperative Oncology Group (ECOG) performance scale 0 to 2.
  • Adequate organic function as defined by the following criteria:
  • serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal of the local laboratory (ULN-LL);
  • Total serum bilirubin ≤ 2.0 x ULN-LL;
  • Absolute neutrophil count ≥ 1,500 / mm^3;
  • Platelet count ≥ 100,000 / mm^3;
  • Hemoglobin ≥ 9.0 g / dL;
  • Estimated creatinine clearance by the Modification of Diet in Renal Disease (MDRD) equation ≥ 60ml / min
  • Term of free and informed consent signed by the patient or legal representative.

Who cannot join

  • Patients already treated with MIBG-I131.
  • A history of serious clinical or psychiatric illness that, by clinical judgment, may involve participation risk in this study.
  • Patients participating in other protocols with experimental drugs.
  • Patients who underwent major recent surgery less than 4 weeks previously.
  • Patients receiving chemotherapy or other oncologic therapy for less than 3 weeks.
  • Pregnant or lactating patients.
  • Another synchronous neoplasm that requires systemic treatment.

Trial locations and contacts

1 site in 1 country.

Brazil1 site

  • AC Camargo Cancer Center

    São Paulo, São Paulo, 01509010

Other trials in Brazil

About this study

Official title: Phase II Study of MIBG-I131 (Metaiodobenzylguanidine) in Patients With Well Differentiated Neuroendocrine Tumors and MIBG Positive Scan

This is a single-arm, unicentric, single-stage, phase 2 clinical study of therapeutic metaiodobenzylguanidine (MIBG) for patients with metastatic well-differentiated neuroendocrine tumors and radiological progression or intolerance after standard lines of treatment and with MIBG positive scan.

Read the detailed description

Neuroendocrine tumors (NET) are rare neoplasms, which frequently present metastatic and incurable at diagnosis. In this context, few effective therapies exist. When the disease becomes refractory to standard therapies, treatments with limited efficacy (eg, surgical debulking, cytotoxic chemotherapies, interferon alpha) that could lead to important adverse events are used. Therefore, clinical studies that test new therapeutic strategies in NET patients with refractory disease are needed. Treatment with radiopharmaceuticals have been studied in NET and showed to be promisor. As an example, is the treatment with Lutetium177 octreotate, disponible in Brazil for decades, and one of the most active therapeutic options to NET.

The radiopharmaceutical MIBG-I131 (metaiodobenzylguanidine linked to Iodine131) is the first treatment choice for patients with paraganglioma/pheochromocytoma (PggF), a rare type of neuroendocrine neoplasm originated from neural ganglia. Patients with this neoplasia are submitted to scintigraphy with MIBG-I131, a norepinephrine analog whose transporter protein is highly expressed in this tumor. If the uptake is positive, patients receive treatment with therapeutic doses of MIBG-I131. The disease control with this intervention could last two years. Old and small studies suggested that MIBG-I131 could also have an activity in other NET besides PggF. Gastrointestinal (GI) or lung NET could have a positive expression on MIBG-I131 scan in up to 50% of the cases. With this rationale, retrospective series reported that MIBG-I131 could offer clinical benefit in patients with GI NET, with disease control in up to 80% of the cases. However, the literature regarding therapeutic MIBG-I131 to NET not PggF is scarce, heterogeneous regarding population, methods of response assessment, doses of the radiopharmaceutical, and short follow-up time. Therefore, due to the absence of effective therapeutic options for patients with metastatic well-differentiated NET refractory to standard treatments, the evidence that NET can have a positive expression on MIBG-I131 scan, and that small retrospective studies with a low level of evidence suggest a benefit for control disease and improvement of symptoms, the investigators proposed a phase II study of MIBG-I131 to well-differentiated GI or lung NET patients with positive MIBG-I131 scan.

Being tested
MIBG-I131
Keywords
MIBG-I131, Nuclear medicine, Treatment
Medical subject headings
Neuroendocrine Tumors

What participants receive

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

  • MIBG-I131Radiation

    Radiopharmaceutical

Study groups in NCT04831567
Study groupRoleWhat they receive
InterventionalExperimentalThe participants will be submitted to metaiodobenzylguanidine 4 doses of 7.400 Mbq (million of Becquerels) (200 mCi). Each dose will be repeated with a minimum interval of 60 days.
Receives: Radiation: MIBG-I131

What is being measured

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

  1. Disease control rate (DCR) at 6 months after the end of treatment

    Defined by absence of radiological progression in conventional imaging examinations by RECIST 1.1.

    Measured: At 6 months after the end of MIBG-I131 (4 cycles - each cycle is 60 days)

  2. Quality of life measured by questionnaire

    Quality of life questionnaire (QLQ), assessed by the European Organisation for Research and Treatment of Cancer Quality of Life for Neuroendocrine Tumors (EORTC QLQ-GINET21) (score ranging from 0 to 100, with higher scores meaning better state of the patient). Improvement in at least 10% of the baseline score will be considered positive.

    Measured: At 6 months after the end of MIBG-I131 (4 cycles - each cycle is 60 days)

Secondary outcomes (6)

  1. Disease control rate (DCR) at 3 months after the end of treatment

    Defined by absence of radiological progression in conventional imaging examinations by RECIST 1.1.

    Measured: At 3 months after the end of MIBG-I131 (4 cycles - each cycle is 60 days)

  2. Progression-free survival

    Defined by time from day 1 cycle 1 to death from any cause or radiological progression by RECIST 1.1, whichever occurs first. Patients alive and without progression at the time of study analysis will be censored for time-to-event analysis.

    Measured: Trough study completion, an average of 3 years

  3. Radiological response rate

    Assessed by RECIST 1.1 criteria.

    Measured: Trough study completion, an average of 3 years

  4. Rate of Biochemical response

    Defined by at least 30 percent drop in the tumor marker (24-hour urine 5-hydroxyindoleacetic acid (5-HIAA) and/or specific hormone), if functioning syndrome, at any time of treatment in relation to pre-treatment value.

    Measured: Trough study completion, an average of 3 years

  5. Quality of life measured by questionnaires

    Quality of life questionnaire (QLQ), assessed by the European Organisation for Research and Treatment of Cancer Quality of Life for Neuroendocrine Tumors (EORTC QLQ-GINET21) (score ranging from 0 to 100, with higher scores meaning better state of the patient). Improvement in at least 10% of the baseline score will be considered positive.

    Measured: Trough study completion, an average of 3 years

  6. Incidence of Treatment-related Adverse Events assessed by Common Terminology Criteria for Adverse Events (CTCAE)

    Frequency of adverse events of grades 2 or more by CTCAE version 5.0.

    Measured: Trough study completion, an average of 3 years

Timeline

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

  1. First posted5 Apr 2021
  2. Study start4 Feb 2021
  3. Primary completion13 May 2022
  4. Study completion13 May 2022

Why it stopped: No participants enrolled

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is a single-arm, unicentric, single-stage, phase 2 clinical study of therapeutic metaiodobenzylguanidine (MIBG) for patients with metastatic well-differentiated neuroendocrine tumors and radiological progression or intolerance after standard lines of treatment and with MIBG positive scan.
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04831567
Sponsor's protocol ID
3025/20
Acronym
MIBNET
Status last verified
May 2022
First submitted
25 Mar 2021
Last updated
19 May 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Rinke A, Muller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, Mayer C, Aminossadati B, Pape UF, Blaker M, Harder J, Arnold C, Gress T, Arnold R; PROMID Study Group. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol. 2009 Oct 1;27(28):4656-63. doi: 10.1200/JCO.2009.22.8510. Epub 2009 Aug 24.

    PubMed 19704057

  • Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Oberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, Krenning E; NETTER-1 Trial Investigators. Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med. 2017 Jan 12;376(2):125-135. doi: 10.1056/NEJMoa1607427.

    PubMed 28076709

  • Riechelmann RP, Weschenfelder RF, Costa FP, Andrade AC, Osvaldt AB, Quidute AR, Dos Santos A, Hoff AA, Gumz B, Buchpiguel C, Vilhena Pereira BS, Lourenco Junior DM, da Rocha Filho DR, Fonseca EA, Riello Mello EL, Makdissi FF, Waechter FL, Carnevale FC, Coura-Filho GB, de Paulo GA, Girotto GC, Neto JE, Glasberg J, Casali-da-Rocha JC, Rego JF, de Meirelles LR, Hajjar L, Menezes M, Bronstein MD, Sapienza MT, Fragoso MC, Pereira MA, Barros M, Forones NM, do Amaral PC, de Medeiros RS, Araujo RL, Bezerra RO, Peixoto RD, Aguiar S Jr, Ribeiro U Jr, Pfiffer T, Hoff PM, Coutinho AK. Guidelines for the management of neuroendocrine tumours by the Brazilian gastrointestinal tumour group. Ecancermedicalscience. 2017 Jan 26;11:716. doi: 10.3332/ecancer.2017.716. eCollection 2017.

    PubMed 28194228

  • van Hulsteijn LT, Niemeijer ND, Dekkers OM, Corssmit EP. (131)I-MIBG therapy for malignant paraganglioma and phaeochromocytoma: systematic review and meta-analysis. Clin Endocrinol (Oxf). 2014 Apr;80(4):487-501. doi: 10.1111/cen.12341. Epub 2013 Nov 19.

    PubMed 24118038

  • Ezziddin S, Logvinski T, Yong-Hing C, Ahmadzadehfar H, Fischer HP, Palmedo H, Bucerius J, Reinhardt MJ, Biersack HJ. Factors predicting tracer uptake in somatostatin receptor and MIBG scintigraphy of metastatic gastroenteropancreatic neuroendocrine tumors. J Nucl Med. 2006 Feb;47(2):223-33.

    PubMed 16455627

  • Riechelmann RP, Pereira AA, Rego JF, Costa FP. Refractory carcinoid syndrome: a review of treatment options. Ther Adv Med Oncol. 2017 Feb;9(2):127-137. doi: 10.1177/1758834016675803. Epub 2016 Nov 2.

    PubMed 28203303

  • Kane A, Thorpe MP, Morse MA, Howard BA, Oldan JD, Zhu J, Wong TZ, Petry NA, Reiman R Jr, Borges-Neto S. Predictors of Survival in 211 Patients with Stage IV Pulmonary and Gastroenteropancreatic MIBG-Positive Neuroendocrine Tumors Treated with 131I-MIBG. J Nucl Med. 2018 Nov;59(11):1708-1713. doi: 10.2967/jnumed.117.202150. Epub 2018 May 18.

    PubMed 29777005

  • Mulholland N, Chakravartty R, Devlin L, Kalogianni E, Corcoran B, Vivian G. Long-term outcomes of (131)Iodine mIBG therapy in metastatic gastrointestinal pancreatic neuroendocrine tumours: single administration predicts non-responders. Eur J Nucl Med Mol Imaging. 2015 Dec;42(13):2002-12. doi: 10.1007/s00259-015-3116-4. Epub 2015 Jul 5.

    PubMed 26142730

  • Navalkissoor S, Alhashimi DM, Quigley AM, Caplin ME, Buscombe JR. Efficacy of using a standard activity of (131)I-MIBG therapy in patients with disseminated neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2010 May;37(5):904-12. doi: 10.1007/s00259-009-1326-3. Epub 2009 Dec 17.

    PubMed 20016892

  • Bomanji JB, Wong W, Gaze MN, Cassoni A, Waddington W, Solano J, Ell PJ. Treatment of neuroendocrine tumours in adults with 131I-MIBG therapy. Clin Oncol (R Coll Radiol). 2003 Jun;15(4):193-8. doi: 10.1016/s0936-6555(02)00273-x.

    PubMed 12846498

  • Yadegarfar G, Friend L, Jones L, Plum LM, Ardill J, Taal B, Larsson G, Jeziorski K, Kwekkeboom D, Ramage JK; EORTC Quality of Life Group. Validation of the EORTC QLQ-GINET21 questionnaire for assessing quality of life of patients with gastrointestinal neuroendocrine tumours. Br J Cancer. 2013 Feb 5;108(2):301-10. doi: 10.1038/bjc.2012.560. Epub 2013 Jan 15.

    PubMed 23322194

  • Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol. 1998 Jan;16(1):139-44. doi: 10.1200/JCO.1998.16.1.139.

    PubMed 9440735

  • Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365-76. doi: 10.1093/jnci/85.5.365.

    PubMed 8433390

  • Yao JC, Fazio N, Singh S, Buzzoni R, Carnaghi C, Wolin E, Tomasek J, Raderer M, Lahner H, Voi M, Pacaud LB, Rouyrre N, Sachs C, Valle JW, Fave GD, Van Cutsem E, Tesselaar M, Shimada Y, Oh DY, Strosberg J, Kulke MH, Pavel ME; RAD001 in Advanced Neuroendocrine Tumours, Fourth Trial (RADIANT-4) Study Group. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet. 2016 Mar 5;387(10022):968-977. doi: 10.1016/S0140-6736(15)00817-X. Epub 2015 Dec 17.

    PubMed 26703889

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MIBG-I131 in people with Neuroendocrine Tumors, run by AC Camargo Cancer Center at 1 site in Brazil.

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 15 inclusion and 7 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: withdrawn, as of the sponsor's last update on 19 May 2022. 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 Brazil. 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?

The study was withdrawn before enrolling participants, so there are no results.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease control rate (DCR) at 6 months after the end of treatment (time frame: At 6 months after the end of MIBG-I131 (4 cycles - each cycle is 60 days)). The study lists 2 primary outcomes in all. 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 NCT04831567, which also lists 14 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 19 May 2022.

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