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

NCT ID: NCT04831567

Last Updated: 2022-05-19

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-04
• Study Completion Date: 2022-05-13

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.

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.

Conditions

Neuroendocrine Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

MIBG-I131

Intervention Type: RADIATION

Radiopharmaceutical

Interventions

MIBG-I131

Radiopharmaceutical

Intervention Type: RADIATION

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AC Camargo Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Rachel Riechelmann

Head of Medical Oncology Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rachel SP Riechelmann, Phd

Role: PRINCIPAL_INVESTIGATOR

AC Camargo Cancer Center

Locations

AC Camargo Cancer Center

São Paulo, São Paulo, Brazil

Countries

Brazil

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://qol.eortc.org/questionnaire/qlq-ginet21/

EORTC Quality of Life Questionnaire - QLQ-GINET21

Other Identifiers

3025/20

Identifier Type: -

Identifier Source: org_study_id