TheranosticTrials.org

Clinical Trial · NCT04614766

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

Overview

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.

Sponsor

University of Iowa

Phase

Phase 1/2

Contacts

David Bushnell, M.D. (PRINCIPAL_INVESTIGATOR)

ClinicalTrials.gov

NCT04614766

Drug / Compound

DOTATATE

Isotope(s):
Target(s):
  • SSTR2
Ligand Class: Peptides
Chelator: DOTA

MIBG

Isotope(s):
Target(s):
  • NET
Ligand Class: Small Molecules

Eligibility

Inclusion

  • Pathologically confirmed (histology or cytology) malignant neoplasm that is determined to be:
  • Stated willingness to comply with all study procedures and availability for duration of study
  • Agreement to adhere to Lifestyle Considerations throughout study duration
  • a well-differentiated neuroendocrine tumor (i.e. grade 1 or grade 2) with a primary tumor location believed to be midgut, or,
  • Disease measuring ≥ 1.5 cm in diameter on CT or MRI as measured per RECIST
  • Agrees to contraception during therapy.
  • Recommended to receive LUTATHERA® or AZEDRA® therapy
  • Adequate performance status (ECOG of 0 or 1; or KPS of \>70).

Exclusion

  • Therapeutic investigational drug within 4 weeks of C1D1 (imaging agents are acceptable).
  • An individual who meets any of the following criteria will be excluded from participation in this study:
  • Prior peptide-receptor radiotherapy (PRRT).
  • Patient with increased fall risk in the opinion of healthcare professionals
  • Women who are pregnant.
  • 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.To continue on study and receive the combined therapy, a participant's imaging must demonstrate one of the following:
  • 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).
  • Patients unable to discontinue medications known to affect MIBG uptake (unless approved by the PI or designee)
  • History of congestive heart failure with a history of cardiac ejection fraction ≤ 35%.
  • Women who are breast feeding.
  • At least one tumor site where the calculated safe radiation dose to that tumor site is 25% higher using the combined therapy compared to Lutathera aloneParticipants who do not meet this criteria are invited to participate in the comparator arm to receive standard Lutathera treatment as indicated by their physicians.
  • Prior external beam radiation dose of \>16 Gy to the kidneys.
  • At least one tumor that is positive for Azedra but negative for Lutathera in addition to Lutathera positive tumors, or,
  • Prior external beam radiation (including brachytherapy) involving 25% of the bone marrow (excluding scatter doses of 5 Gy) as estimated by a radiation oncologist.
  • 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).
  • Proteinuria grade 2 (i.e., 2+ proteinuria).