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Dosimetry Guided PRRT With 177Lu-DOTATATE in Children

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ClinicalTrials.gov Identifier: NCT03923257
Recruitment Status : Recruiting
First Posted : April 22, 2019
Last Update Posted : August 6, 2020
Sponsor:
Collaborator:
Advanced Accelerator Applications
Information provided by (Responsible Party):
Sue O'Dorisio, University of Iowa

Tracking Information
First Submitted Date  ICMJE March 29, 2019
First Posted Date  ICMJE April 22, 2019
Last Update Posted Date August 6, 2020
Actual Study Start Date  ICMJE August 4, 2020
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 17, 2019)
  • Toxicities [ Time Frame: Initiation of treatment through 5 years ]
    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.
  • Objective Response Rate (ORR) according to RECIST criteria in children [ Time Frame: Initiation of treatment through 5 years ]
    To determine overall response rate (ORR) (complete response [CR] + partial response [PR]) + stable disease [SD] per RECIST v1.1)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 4, 2020)
  • 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 [ Time Frame: Initiation of treatment through treatment #4 (approximately 26 weeks) ]
    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.
  • Measure and demonstrate accuracy of radiation dose to bone marrow in children based on radioactivity in a single blood sample [ Time Frame: Initiation of treatment through treatment #4 (approximately 26 weeks) ]
    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.
  • Progression Free Survival (PFS) according to RECIST criteria in children [ Time Frame: Initiation of treatment through 5 years ]
    Progression will be defined using the RECIST 1.1 guidelines. Results are provided in nominal categories (CR, PR, SD, PD) as per RECIST.
  • Measure effect of PRRT in quality of life with the PROMIS Pediatric Profile v2.0 - Profile-37 [ Time Frame: Initiation of treatment through treatment #4 (approximately 26 weeks) ]
    Parents of participants will be asked to complete the PROMIS Pediatric Profile v2.0 - Profile-37
Original Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2019)
  • 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 [ Time Frame: Initiation of treatment through treatment #4 (approximately 26 weeks) ]
    Six subjects in each group 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.
  • Measure and demonstrate accuracy of radiation dose to bone marrow in children based on radioactivity in a single blood sample [ Time Frame: Initiation of treatment through treatment #4 (approximately 26 weeks) ]
    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.
  • Progression Free Survival (PFS) according to RECIST criteria in children [ Time Frame: Initiation of treatment through 5 years ]
    Progression will be defined using the RECIST 1.1 guidelines. Results are provided in nominal categories (CR, PR, SD, PD) as per RECIST.
  • Measure effect of PRRT in quality of life with the PROMIS Pediatric Profile v2.0 - Profile-37 [ Time Frame: Initiation of treatment through treatment #4 (approximately 26 weeks) ]
    Parents of participants will be asked to complete the PROMIS Pediatric Profile v2.0 - Profile-37
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dosimetry Guided PRRT With 177Lu-DOTATATE in Children
Official Title  ICMJE Phase I Trial of Peptide Receptor Radiotherapy (PRRT) With 177Lu-DOTA-tyr3-Octreotate (177Lu-DOTATATE) in Children With Neuroendocrine Tumor or Pheochromocytoma/Paraganglioma
Brief Summary This is a Phase I/II peptide receptor radiotherapy (PRRT) trial of 177Lu-DOTA-OCTREOTATE in children with neuroendocrine tumors and pheochromocytoma or paraganglioma.
Detailed Description

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

This study will consists of children age 18 months to 18 years with relapsed or refractory neuroendocrine tumors and pheochromocytoma or paraganglioma.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Neuroendocrine Tumors
  • Pheochromocytoma
  • Paraganglioma
Intervention  ICMJE
  • Drug: 177Lu-DOTA-tyr3-OCTREOTATE
    This is a peptide receptor radiotherapy that targets somatostatin receptors on tumor cells.
    Other Name: Lutathera
  • Procedure: Peptide Receptor Radiotherapy (PRRT)
    PRRT is internal radiation that is individually dosed according to patient body surface area, kidney function and bone marrow status.
Study Arms  ICMJE Experimental: PRRT with 177Lu-DOTA-tyr3-OCTREOTATE

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 age 18 months to 18 years with relapsed or refractory neuroendocrine tumors and pheochromocytoma or paraganglioma. Children with neuroendocrine tumor, pheochromocytoma or paraganglioma will not have had any previous endoradiotherapy with 90Y-DOTATOC, 131I-MIBG, or 177Lu-DOTATATE.

Interventions:
  • Drug: 177Lu-DOTA-tyr3-OCTREOTATE
  • Procedure: Peptide Receptor Radiotherapy (PRRT)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 17, 2019)
74
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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 are required.
  • 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 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 measurable 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 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 to less than 18 years at the time of first study drug administration.
  • Performance status as determined by Karnofsky of at least 60 or Lansky Play Scale of at least 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 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) of at least 1000/mm3
  • Platelet count of at least 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 creatinine, BUN, potassium, sodium, chloride, bicarbonate, magnesium, phosphorus, calcium, glucose Normal for age Glomerular filtration rate (GFR) using Nuclear GFR or CrCl if creatinine greater than normal for age/sex; if required, GFR must be at least 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 <7 years of age. Children 7-13 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.

Exclusion Criteria:

  • 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 less than 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 18-24 hrs prior to injection of study drug.
  • 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, at least 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:

    1. 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).
    2. Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or ANC counts): at least 7 days after the last dose of agent.
    3. Antibodies: at least 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.
    4. Hematopoietic growth factors: at least 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.
    5. Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): at least 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors).
    6. Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion or boost infusion: at least 84 days after stem cell infusion
    7. Evidence of GVHD.
    8. Autologous stem cell infusion including boost infusion: at least 42 days; cellular therapy: at least 42 days after the completion of any type of cellular therapy (e.g. modified T cells, NK cells, dendritic cells, etc.).
  • Inclusion of Women and Minorities Both male and female members of all ethnic groups are eligible for this trial.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: M. Sue O'Dorisio, MD, PhD 319-335-7234 sue-odorisio@uiowa.edu
Contact: Silvia Ghobrial, MD silvia-ghobrial@uiowa.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03923257
Other Study ID Numbers  ICMJE 201812772
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sue O'Dorisio, University of Iowa
Study Sponsor  ICMJE Sue O'Dorisio
Collaborators  ICMJE Advanced Accelerator Applications
Investigators  ICMJE
Principal Investigator: M. Sue O'Dorisio, MD, PhD University of Iowa
PRS Account University of Iowa
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP