A Clinical Trial Evaluating the Safety of Combining Lutathera(R) and Azedra(R) to Treat Mid-gut Neuroendocrine Tumors

NCT04614766 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 202005556P50CA174521
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to identify the best tolerated doses of Lutathera® and Azedra® when co-administered to treat midgut neuroendocrine tumors. These drugs are radioactive drugs, known as radionuclide therapy, and are both approved in the treatment of midgut neuroendocrine tumor as single agents (not together). Currently, the safest and best tolerated doses of these drugs (when combined) is unknown. That is the purpose of this clinical trial.

Conditions

Gastro-enteropancreatic Neuroendocrine Tumor; Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (4)

• Phase 1: Determination of maximum tolerated radiation dose (MTD) to the kidneys

  MTD will be determined by incidence of renal AEs as characterized by type, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.

  9 months after initial treatment

• Phase 1: Determination of maximum tolerated radiation dose (MTD) to the bone marrow.

  MTD will be determined by incidence of hematologic AEs as characterized by type, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.

  9 months

• Phase 2: Objective Response Rate (ORR)

  Objective response rate, measured using standardized RECIST criteria, is a reflection of complete tumor response and partial tumor response when obtained at 6 months and 12 months post-treatment.

  6 months post-treatment

• Phase 2: Objective Response Rate (ORR)

  Objective response rate, measured using standardized RECIST criteria, is a reflection of complete tumor response and partial tumor response when obtained at 6 months and 12 months post-treatment.

  12 months post-treatment

Secondary Outcomes (3)

• Tumor size

  6 months post-treatment

• Tumor size

  12 months post-treatment

• Number of Treatment-Related Adverse Events

  Up to 24 months post-treatment

Study Arms (2)

Combination Therapy

EXPERIMENTAL

Combined treatment with Lutathera® and Azedra® Administered amounts of each drug are based on imaging and radiation dose constraints to the kidneys and the bone marrow. The drug administration is individualized to each participant.

Drug: Lutathera; Drug: Azedra

Lutathera® only

ACTIVE COMPARATOR

Single agent Lutathera® administered per standard of care: 200 millicuries of drug every 8 weeks for a total of 4 doses.

Drug: Lutathera

Interventions

Lutathera DRUG

intravenous administration

Also known as: lutetium Lu 177 dotatate

Combination Therapy; Lutathera® only

Azedra DRUG

intravenous administration

Also known as: iobenguane I-131

Combination Therapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and willingness to provide informed consent; legally authorized representative will not be utilized compliant with the principles of good clinical practice (i.e., ICH E6(R2)).
• Stated willingness to comply with all study procedures and availability for duration of study
• Aged ≥ 18 years to 80 years at the time of study drug administration
• Pathologically confirmed (histology or cytology) malignant neoplasm that is determined to be:
• a well-differentiated neuroendocrine tumor (i.e. grade 1 or grade 2) with a primary tumor location believed to be midgut, or,
• pheochromocytoma, or,
• paraganglioma
• Recommended to receive LUTATHERA® or AZEDRA® therapy
• Disease measuring ≥ 1.5 cm in diameter on CT or MRI as measured per RECIST
• Adequate performance status (ECOG of 0 or 1; or KPS of \>70).
• Agrees to contraception during therapy.
• Agreement to adhere to Lifestyle Considerations throughout study duration

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Patient with increased fall risk in the opinion of healthcare professionals
• Women who are pregnant.
• Women who are breast feeding.
• Surgery, radiation therapy, or chemotherapy ≤ 4 weeks of C1D1. (Toxicities from prior therapies should have resolved to ≤ CTCAE grade 1 or a new baseline established).
• Prior peptide-receptor radiotherapy (PRRT).
• Therapeutic investigational drug within 4 weeks of C1D1 (imaging agents are acceptable).
• A concurrent malignancy that, in the opinion of the investigator, would cause a safety risk by delaying therapy or confound/negatively impact study objectives (documentation of the rationale must be provided).
• History of congestive heart failure with a history of cardiac ejection fraction ≤ 35%.
• Patients unable to discontinue medications known to affect MIBG uptake (unless approved by the PI or designee)
• Proteinuria grade 2 (i.e., 2+ proteinuria).
• Prior external beam radiation dose of \>16 Gy to the kidneys.
• Prior external beam radiation (including brachytherapy) involving 25% of the bone marrow (excluding scatter doses of 5 Gy) as estimated by a radiation oncologist.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Octreoscan® or Netspot™.
• Participants meeting the above criteria will receive one cycle of standard Lutathera treatment (200 millicuries) as well as a tracer dose of Azedra for imaging. Participants will then undergo protocol specific imaging to calculate the radiation dose to the kidneys, the bone marrow, and to the tumor lesions.

Sponsors & Collaborators

• David Bushnell: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator
• Progenics Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Related Publications (2)

• Madsen MT, Bushnell DL, Juweid ME, Menda Y, O'Dorisio MS, O'Dorisio T, Besse IM. Potential increased tumor-dose delivery with combined 131I-MIBG and 90Y-DOTATOC treatment in neuroendocrine tumors: a theoretic model. J Nucl Med. 2006 Apr;47(4):660-7.

  PMID: 16595501 BACKGROUND

• Bushnell DL, Madsen MT, O'cdorisio T, Menda Y, Muzahir S, Ryan R, O'dorisio MS. Feasibility and advantage of adding (131)I-MIBG to (90)Y-DOTATOC for treatment of patients with advanced stage neuroendocrine tumors. EJNMMI Res. 2014 Dec;4(1):38. doi: 10.1186/s13550-014-0038-2. Epub 2014 Sep 10.

  PMID: 26116109 BACKGROUND

MeSH Terms

Conditions

Gastro-enteropancreatic neuroendocrine tumor; Neuroendocrine Tumors

Interventions

lutetium Lu 177 dotatate; 3-Iodobenzylguanidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Iodobenzenes; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Hydrocarbons, Iodinated; Hydrocarbons, Halogenated

Study Officials

• David Bushnell, M.D.

  The University of Iowa and the Iowa City VAMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Participants who do not meet eligibility criteria for the combined therapy will be asked to participate in the active comparator, which is single agent Lutathera administered as per FDA guidelines.

Study Record Dates

• First Submitted: October 13, 2020
• First Posted: November 4, 2020
• Study Start: September 30, 2022
• Primary Completion: April 23, 2024
• Study Completion: April 23, 2024
• Last Updated: April 29, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: phase 1 data: 12 months after identifying the maximum dose phase 2 data: 12 months after last participant last visit
• Access Criteria: A data usage agreement and privacy contract will need to be completed between investigators and their institutions. Data are to be destroyed after completion / use.

Locations

US (1)