Clinical Trials /

Dosimetry Guided PRRT With 177Lu-DOTATATE in Children

NCT03923257

Description:

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

Related Conditions:
  • Adrenal Gland Pheochromocytoma
  • Neuroblastoma
  • Neuroendocrine Tumor
  • Paraganglioma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Dosimetry Guided PRRT With 177Lu-DOTATATE in Children
  • Official Title: Phase I/II Trial of Peptide Receptor Radiotherapy (PRRT) With 177Lu-DOTA-tyr3 OCTREOTATE (177Lu-DOTATATE) in Children With Neuroendocrine Tumor, Neuroblastoma, or Pheochromocytoma/Paraganglioma

Clinical Trial IDs

  • ORG STUDY ID: 201812772
  • NCT ID: NCT03923257

Conditions

  • Neuroendocrine Tumors
  • Neuroblastoma
  • Pheochromocytoma
  • Paraganglioma

Interventions

DrugSynonymsArms
177Lu-DOTA-tyr3-OCTREOTATELutatheraPRRT with 177Lu-DOTA-tyr3-OCTREOTATE

Purpose

This is a Phase I/II peptide receptor radiotherapy (PRRT) trial of 177Lu-DOTA-OCTREOTATE in children with relapsed or refractory neuroblastoma, 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 two groups:

      Group A - children age 18 months to 18 years with relapsed or refractory neuroendocrine
      tumors and pheochromocytoma or paraganglioma.

      Group B - children age 6 months to 18 years with relapsed or refractory neuroblastoma.
    

Trial Arms

NameTypeDescriptionInterventions
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 consists of two groups: Group A - 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. Group B - Children age 6 months to 18 years with relapsed or refractory neuroblastoma. Children with neuroblastoma may have received previous 131I-MIBG treatment and must have dosimetry estimates of that radiation dose before receiving 177Lu-DOTATATE therapy in this study.
  • 177Lu-DOTA-tyr3-OCTREOTATE

Eligibility Criteria

        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.

          -  A pathologically confirmed (histology or cytology) Neuroendocrine Tumor (NET),
             Neuroblastoma (NB), 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.

          -  For patients with neuroblastoma, If the patient has only one MIBG positive lesion and
             that lesion was radiated, a biopsy or 18FDG PET scan must be done at least 28 days
             after radiation was completed and must show viable neuroblastoma. Such a lesion is not
             sufficient for eligibility if no lesions are positive for 68Ga- DOTATATE PET/CT.

          -  No previous endogenous radiation with 177Lu-DOTATATE/TOC or 90Y-DOTATATE/TOC within 12
             months of most recent treatment. Previous treatment must be limited to ≤40 Gy
             biologically effective dose (BED) to kidneys and ≤2 Gy to bone marrow; hematopoietic
             stem cells (HSC) ≥2X106 CD34+ cells/kg must be available if >2 Gy prior exposure to
             bone marrow.

          -  Previous treatment of neuroblastoma with 131I-MIBG must be limited to ≤40 Gy
             biologically effective dose (BED) to kidneys and ≤3 Gy to bone marrow; hematopoietic
             stem cells (HSC) ≥2X106 CD34+ cells/kg must be available if >3 Gy prior exposure to
             bone marrow.

          -  Age 18 months-18 years except neuroblastoma with amplified NMYC may be eligible at 6
             months.

          -  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 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) ≥750/mm3

          -  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

          -  Creatinine, BUN, potassium, sodium, chloride, bicarbonate, magnesium, phosphorus,
             calcium, glucose; Normal for age

          -  Glomerular filtration rate (GFR); 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 ≤7 years of age. Children ≥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.

        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 ˂50% of a single kidney is acceptable).

          -  Prior PRRT with 90Y-DOTATOC (TATE) or 177Lu-DOTATOC (TATE) 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.

          -  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 corticosteroids 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.

               -  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)Stem cell Infusions (with or without
                  TBI).

               -  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.).
      
Maximum Eligible Age:18 Years
Minimum Eligible Age:6 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Toxicities
Time Frame:Initiation of treatment through 5 years
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description: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: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)
Safety Issue:
Description: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.
Measure:Progression Free Survival (PFS) according to RECIST criteria in children
Time Frame:Initiation of treatment through 5 years
Safety Issue:
Description:Progression will be defined using the RECIST 1.1 guidelines. Results are provided in nominal categories (CR, PR, SD, PD) as per RECIST.
Measure: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)
Safety Issue:
Description:Parents of participants will be asked to complete the PROMIS Pediatric Profile v2.0 - Profile-37

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sue O'Dorisio

Last Updated

April 19, 2019