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Neuroendocrine TumorsPhase 1/2NCT03923257

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

A Phase 1/2 study testing 177Lu-DOTA-tyr3-OCTREOTATE and Peptide Receptor Radiotherapy (PRRT) in people with Neuroendocrine Tumors and Pheochromocytoma, run by Sue O'Dorisio at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 1 year to 20 years
What is being tested?
177Lu-DOTA-tyr3-OCTREOTATE and Peptide Receptor Radiotherapy (PRRT)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
4 Aug 2020to 3 Jun 2021
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 20 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
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  • 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)
  • Hemoglobin ≥ 8g/dL Organ Function Requirements
  • AST(SGOT)\& ALT(SGPT) <10X institutional upper limit of normal for age
  • Total bilirubin <3X ULN for age
  • BUN < 2X normal
  • creatinine, Normal for age
  • Glomerular filtration rate (GFR) only if creatinine > normal for age
  • Nuclear GFR or CrCl ≥ 80 ml/min/1.73m2
  • Urinalysis No greater than 1+ hematuria or proteinuria
  • The effects of 177Lu-DOTATATE on the developing human fetus are unknown. For this reason and because Class C agents are known to be teratogenic, all subjects capable of becoming pregnant must agree to practice a medically acceptable birth control measure (abstinence, birth control pills, intrauterine devices, vaginal diaphragm, vaginal sponge, or condom with spermicidal jelly) throughout the study and for eight months following the end of the last treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Parent's ability to understand and the willingness to sign a written informed consent document for children < seven (7) years of age. Children ≥ seven (7) years of age will sign assent along with parental consent or will co-sign consent with parent in accordance with rules of the state in which treatment is received.

Who cannot join

  • 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.
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  • 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:
  • Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. At least 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea).
  • Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or ANC counts): ≥ 7 days after the last dose of agent. Short-acting somatostatin analogue may be administered up to eight hours prior to infusion of study drug.
  • Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
  • Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g. Peg-Filgrastim) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator.
  • Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors).
  • Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion or boost infusion: ≥ 84 days after stem cell infusion
  • Evidence of GVHD.
  • Autologous stem cell infusion including boost infusion: ≥ 42 days; cellular therapy: ≥ 42 days after the completion of any type of cellular therapy (e.g. modified T cells, NK cells, dendritic cells, etc.).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

Other trials in United States

About this study

Official title: Phase I Trial of Peptide Receptor Radiotherapy (PRRT) With 177Lu-DOTA-tyr3-Octreotate (177Lu-DOTATATE) in Children and Adolescents With Neuroendocrine Tumor or Pheochromocytoma/Paraganglioma

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.

Read the detailed description

The purpose of this clinical trial is to determine if peptide receptor radiotherapy (PRRT) using 177Lu-DOTA-OCTREOTATE given intravenously in children and adolescents is an effective treatment and to describe its toxicities.

This study will consists of children and adolescents ages 1-20 years with relapsed or refractory neuroendocrine tumors and pheochromocytoma or paraganglioma.

Being tested
177Lu-DOTA-tyr3-OCTREOTATE, Peptide Receptor Radiotherapy (PRRT)
Medical subject headings
Neuroendocrine Tumors, Pheochromocytoma, Paraganglioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 177Lu-DOTA-tyr3-OCTREOTATEDrug

    Also called Lutathera

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

  • Peptide Receptor Radiotherapy (PRRT)Procedure or surgery

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

Study groups in NCT03923257
Study groupRoleWhat they receive
PRRT with 177Lu-DOTA-tyr3-OCTREOTATEExperimental177Lu-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.
Receives: Drug: 177Lu-DOTA-tyr3-OCTREOTATE; Procedure: Peptide Receptor Radiotherapy (PRRT)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Initiation of treatment through 5 years

  2. 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)

    Measured: Initiation of treatment through 5 years

Secondary outcomes (4)

  1. 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

    Six subjects will have whole body imaging and SPECT/CT of kidneys performed at 3-8 hours plus whole body and SPECT at 20-28 hours, 44-52 hours, 92-100 hours and 116-124 hours after the administration of the radiopharmaceutical. Data will be analyzed using method of Madsen[1,2]. Single point dosimetry will be utilized with subsequent cohorts if data demonstrates agreement with adult dosimetry. Biological effective dose (BED) to kidneys will be calculated according to Bodei et al [3].

    The information on renal uptake, renal mass and residence time will be entered into OLINDA software to calculate the radiation dose. If single point dosimetry proves to be accurate, any remaining Phase I subjects and all Phase II subjects will receive single point dosimetry for both renal and bone marrow radiation dose estimation.

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

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

    Blood dosimetry will be performed as a surrogate of bone marrow dosimetry. Blood samples (1 mL) will be obtained prior to start of amino acid infusion and subsequently in the same time frame with the imaging sessions.

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

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

    Progression will be defined using the RECIST 1.1 guidelines. Results are provided in nominal categories (CR, PR, SD, PD) as per RECIST.

    Measured: Initiation of treatment through 5 years

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

    Parents of participants will be asked to complete the PROMIS Pediatric Profile v2.0 - Profile-37

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Apr 2019
  2. Study start4 Aug 2020
  3. Primary completion3 Jun 2021
  4. Study completion3 Jun 2021

Why it stopped: competing clinical trial opening

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03923257
Sponsor's protocol ID
201812772
Status last verified
Jun 2021
First submitted
29 Mar 2019
Last updated
8 Jun 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 29577338

  • 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.

    PubMed 29523629

  • 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.

    PubMed 18427807

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing 177Lu-DOTA-tyr3-OCTREOTATE and Peptide Receptor Radiotherapy (PRRT) in people with Neuroendocrine Tumors and Pheochromocytoma, run by Sue O'Dorisio at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 8 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Toxicities (time frame: Initiation of treatment through 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03923257, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2021.

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