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

Sponsor
AC Camargo Cancer Center (Other)
Overall Status
Withdrawn
CT.gov ID
NCT04831567
Collaborator
(none)
0
Enrollment
1
Location
1
Arm
15.2
Actual Duration (Months)
0
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
  • Radiation: MIBG-I131
 Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
0 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention 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.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)
Primary Purpose:
Treatment
Official Title:
Phase II Study of MIBG-I131 (Metaiodobenzylguanidine) in Patients With Well Differentiated Neuroendocrine Tumors and MIBG Positive Scan
Actual Study Start Date :
Feb 4, 2021
Actual Primary Completion Date :
May 13, 2022
Actual Study Completion Date :
May 13, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Interventional

The 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.

Radiation: MIBG-I131
Radiopharmaceutical

Outcome Measures

Primary Outcome Measures

  1. Disease control rate (DCR) at 6 months after the end of treatment [At 6 months after the end of MIBG-I131 (4 cycles - each cycle is 60 days)]

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

  2. Quality of life measured by questionnaire [At 6 months after the end of MIBG-I131 (4 cycles - each cycle is 60 days)]

    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.

Secondary Outcome Measures

  1. Disease control rate (DCR) at 3 months after the end of treatment [At 3 months after the end of MIBG-I131 (4 cycles - each cycle is 60 days)]

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

  2. Progression-free survival [Trough study completion, an average of 3 years]

    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.

  3. Radiological response rate [Trough study completion, an average of 3 years]

    Assessed by RECIST 1.1 criteria.

  4. Rate of Biochemical response [Trough study completion, an average of 3 years]

    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.

  5. Quality of life measured by questionnaires [Trough study completion, an average of 3 years]

    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.

  6. Incidence of Treatment-related Adverse Events assessed by Common Terminology Criteria for Adverse Events (CTCAE) [Trough study completion, an average of 3 years]

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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • 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

  • 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.

Exclusion Criteria:

  • 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 AC Camargo Cancer Center São Paulo SP Brazil 01509010

Sponsors and Collaborators

  • AC Camargo Cancer Center

Investigators

  • Principal Investigator: Rachel SP Riechelmann, Phd, AC Camargo Cancer Center

Study Documents (Full-Text)

More Information

Additional Information:

Publications

Responsible Party:
Rachel Riechelmann, Head of Medical Oncology Department, AC Camargo Cancer Center
ClinicalTrials.gov Identifier:
NCT04831567
Other Study ID Numbers:
  • 3025/20
First Posted:
Apr 5, 2021
Last Update Posted:
May 19, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by Rachel Riechelmann, Head of Medical Oncology Department, AC Camargo Cancer Center
MIBG-I131
Nuclear medicine
Treatment
Additional relevant MeSH terms:
Neuroendocrine Tumors

Study Results

No Results Posted as of May 19, 2022