Dosimetry Guided PRRT With 177Lu-DOTATATE in Children and Adolescents

NCT03923257 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 201812772
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I/II peptide receptor radiotherapy (PRRT) trial of 177Lu-DOTA-OCTREOTATE in children and adolescents with neuroendocrine tumors and pheochromocytoma or paraganglioma.

Conditions

Neuroendocrine Tumors; Pheochromocytoma; Paraganglioma

Outcome Measures

Primary Outcomes (2)

• Toxicities

  To examine the toxicity related to the therapy by measuring the number of treatment related adverse events in patients Adverse events will be reported in tabular form by type and grade. Adverse events will be graded according to the most recent CTE guidelines.

  Initiation of treatment through 5 years

• Objective Response Rate (ORR) according to RECIST criteria in children

  To determine overall response rate (ORR) (complete response \[CR\] + partial response \[PR\]) + stable disease \[SD\] per RECIST v1.1)

  Initiation of treatment through 5 years

Secondary Outcomes (4)

• Measure and demonstrate accuracy of radiation dose to kidneys in children based on a single SPECT/CT image of the kidneys plus a single whole body scan

  Initiation of treatment through treatment #4 (approximately 26 weeks)

• Measure and demonstrate accuracy of radiation dose to bone marrow in children based on radioactivity in a single blood sample

  Initiation of treatment through treatment #4 (approximately 26 weeks)

• Progression Free Survival (PFS) according to RECIST criteria in children

  Initiation of treatment through 5 years

• Measure effect of PRRT in quality of life with the PROMIS Pediatric Profile v2.0 - Profile-37

  Initiation of treatment through treatment #4 (approximately 26 weeks)

Study Arms (1)

PRRT with 177Lu-DOTA-tyr3-OCTREOTATE

EXPERIMENTAL

177Lu-DOTA-tyr3-OCTREOTATE (177Lu-DOTATATE) and amino acid will be administered intravenously (IV) on Day 1 of each of four treatment cycles, 8 weeks apart. This study will consist of children and adolescents ages 1-20 years with relapsed or refractory neuroendocrine tumors and pheochromocytoma or paraganglioma. Children and adolescents with neuroendocrine tumor, pheochromocytoma or paraganglioma will not have had any previous endoradiotherapy with 90Y-DOTATOC, 131I-MIBG, or 177Lu-DOTATATE.

Drug: 177Lu-DOTA-tyr3-OCTREOTATE; Procedure: Peptide Receptor Radiotherapy (PRRT)

Interventions

177Lu-DOTA-tyr3-OCTREOTATE DRUG

This is a peptide receptor radiotherapy that targets somatostatin receptors on tumor cells.

Also known as: Lutathera

PRRT with 177Lu-DOTA-tyr3-OCTREOTATE

Peptide Receptor Radiotherapy (PRRT) PROCEDURE

PRRT is internal radiation that is individually dosed according to patient body surface area, kidney function and bone marrow status.

PRRT with 177Lu-DOTA-tyr3-OCTREOTATE

Eligibility Criteria

• Age: 1 Year - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Disease not amenable to standard treatment (nonresectable or disease present after one or more surgeries and/or Sandostatin treatment) or subject has failed existing first line chemotherapy, biologic therapy, targeted agent therapy or radiation therapy.
• Participation in Iowa Neuroendocrine Tumor Registry and recommendation by University of Iowa PRRT tumor board.
• A pathologically confirmed (histology or cytology) Neuroendocrine Tumor (NET), Pheochromocytoma (PCC), or Paraganglioma (PGL).
• For patients with measurable or evaluable disease: \>50% of lesions must demonstrate 68Ga-DOTATATE /DOTATOC uptake greater than physiologic liver uptake by visual assessment. At least one lesion must be confirmed by conventional imaging (CT or MRI).
• For patients with measurable disease, the target lesion is one that either has never received external beam radiation or has been previously irradiated and has since demonstrated progression.
• For patients with no measurable disease (no meaurable target lesions), who have evaluable disease (bone disease, MIBG positive disease, liver metastases not detectable on MRI or CT), the disease must be seen on 68Ga-DOTATATE/DOTATOC PET/CT.
• No previous endogenous radiation with 177Lu-DOTATATE/TOC or 90Y-DOTATATE/TOC or 131I-MIBG within 12 months of most recent treatment.
• Age ≥ 18 months \< 20 years at the time of first study drug administration.
• Performance status as determined by Karnofsky ≥ 60 or Lansky Play Scale ≥ 60 at the time of study drug administration.
• NOTE: Neurologic deficits in patients with brain metastases must have been stable for at least 7 days prior to study enrollment.
• Completion of validated Pediatric Quality of Life Questionnaire.
• Within seven (7) days of study drug administration, must have normal organ and bone marrow function as defined below:
• Adequate Bone Marrow Function Defined as:
• Peripheral absolute neutrophil count (ANC) ≥ 1000/m3
• Platelet count ≥ 75,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)

You may not qualify if:

• Pregnant women are excluded from this study because 177Lu-DOTATATE is a Class C agent with potential teratogenic or abortifacient effects.
• Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 177Lu-DOTATATE, breastfeeding should be discontinued until 3 months after the last administration of study drug.
• Major surgery within 8 weeks of study drug administration.
• External beam radiation to both kidneys (scatter doses of \<500 cGy to a single kidney or radiation to \< 50% of a single kidney is acceptable).
• Prior PRRT with 90Y-DOTATOC (TATE) or 177Lu-DOTATOC (TATE) or 131I-MIBG for this malignancy within 12 months of first study dose.
• Another investigational drug within 8 weeks of study drug administration.
• Concurrent, malignant disease for which patient is on active therapy.
• Another significant medical, psychiatric, or surgical condition which is currently uncontrolled by treatment and which would likely affect the subject's ability to complete this protocol.
• Subjects who have received Sandostatin LAR or long-acting lanreotide in the past 28 days must be appropriately delayed. Subjects may be maintained on short acting octreotide during the time from last injection of long-acting somatostatin analogue until 8-24 hrs prior to injection of study drug.
• Known antibodies to Octreotide, Lanreotide, or DOTATATE or history of allergic reactions attributed to compounds of similar chemical or biologic composition to 177Lu-DOTATATE.
• Uncontrolled illness including, but not limited to ongoing or active infection, uncontrolled diabetes mellitus, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, hepatic cirrhosis or severe impairment, or psychiatric illness/social situations that would limit compliance with study requirements.
• Corticosteroids: Patients receiving corticosterods who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, ≥ 14 days must have elapsed since last dose of corticosteroid
• Patients who have received a prior solid organ transplantation are not eligible
• Patients will be excluded if they have a known allergy to any of the drugs used in the study
• Prior Therapy:

Sponsors & Collaborators

• Sue O'Dorisio: lead
• Advanced Accelerator Applications: collaborator

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Related Publications (3)

• Madsen MT, Menda Y, O'Dorisio TM, O'Dorisio MS. Technical Note: Single time point dose estimate for exponential clearance. Med Phys. 2018 May;45(5):2318-2324. doi: 10.1002/mp.12886. Epub 2018 Apr 16.

  PMID: 29577338 BACKGROUND

• Menda Y, Madsen MT, O'Dorisio TM, Sunderland JJ, Watkins GL, Dillon JS, Mott SL, Schultz MK, Zamba GKD, Bushnell DL, O'Dorisio MS. 90Y-DOTATOC Dosimetry-Based Personalized Peptide Receptor Radionuclide Therapy. J Nucl Med. 2018 Nov;59(11):1692-1698. doi: 10.2967/jnumed.117.202903. Epub 2018 Mar 9.

  PMID: 29523629 BACKGROUND

• Bodei L, Cremonesi M, Ferrari M, Pacifici M, Grana CM, Bartolomei M, Baio SM, Sansovini M, Paganelli G. Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors. Eur J Nucl Med Mol Imaging. 2008 Oct;35(10):1847-56. doi: 10.1007/s00259-008-0778-1. Epub 2008 Apr 22.

  PMID: 18427807 BACKGROUND

MeSH Terms

Conditions

Neuroendocrine Tumors; Pheochromocytoma; Paraganglioma

Interventions

lutetium Lu 177 dotatate

Condition Hierarchy (Ancestors)

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

Study Officials

• M. Sue O'Dorisio, MD, PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 29, 2019
• First Posted: April 22, 2019
• Study Start: August 4, 2020
• Primary Completion: June 3, 2021
• Study Completion: June 3, 2021
• Last Updated: June 8, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)