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Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With GEP-NETs and PPGLs

NCT04711135

Description:

This is a multicenter, open-label, single-arm study to evaluate the safety and dosimetry of Lutathera in adolescent patients 12 to <18 years old with somatostatin receptor positive GEP-NETs and PPGLs. The study will enroll at least 8 patients in the GEP-NET cohort and as many adolescents with PPGL as possible in the exploratory PPGL cohort.

Related Conditions:
  • Adrenal Gland Pheochromocytoma
  • Gastrointestinal Neuroendocrine Tumors
  • Paraganglioma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With GEP-NETs and PPGLs
  • Official Title: A Multicenter Open-label Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With Somatostatin Receptor Positive Gastroenteropancreatic Neuroendocrine (GEP-NET) Tumors, Pheochromocytoma and Paragangliomas (PPGL)

Clinical Trial IDs

  • ORG STUDY ID: CAAA601A32201
  • SECONDARY ID: 2020-002951-39
  • NCT ID: NCT04711135

Conditions

  • Gastroenteropancreatic Neuroendocrine Tumors
  • Pheochromocytoma
  • Paraganglioma

Interventions

DrugSynonymsArms
Lutetium [177Lu] oxodotreotide/dotatateLutatheraGEP-NET and PPGL

Purpose

This is a multicenter, open-label, single-arm study to evaluate the safety and dosimetry of Lutathera in adolescent patients 12 to <18 years old with somatostatin receptor positive GEP-NETs and PPGLs. The study will enroll at least 8 patients in the GEP-NET cohort and as many adolescents with PPGL as possible in the exploratory PPGL cohort.

Detailed Description

      The study schedule for each patient consists of the screening period (up to 2 weeks) followed
      by the treatment period (4 treatment administrations at 8-week interval), and the follow-up
      period (5 years).

      The treatment period will consist of 4 Lutathera treatments administered at 8-week intervals.
      Lutathera administration will occur on Week 1 Day 1 of each cycle. Each patient will receive
      a total of 4 doses of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8 weeks;
      cumulative dose: 29.6 GBq/800 mCi). An infusion of 2.5% Lysine - Arginine amino acid (AA)
      solution will be co-administered with each Lutathera dose for renal protection according to
      the approved Lutathera local prescribing information. An antiemetic will be administered
      prior to infusion of the AA solution for prevention of infusion-related nausea and vomiting.

      The dosimetry and PK assessments will be performed during the first week after the 1st
      Lutathera dose, i.e. one time during the study treatment period for each patient. The
      dosimetry analysis will allow for estimation from the 1st Lutathera administration of the
      cumulative absorbed radiation dose from 4 Lutathera doses and also for taking a decision on
      the next dose levels. In the exceptional circumstances when dosimetry cannot be performed in
      a particular patient after the first Lutathera dose, it should be completed as soon as
      feasible upon a later dose. In order to minimize risk for each study subject, an accelerated
      analysis of dosimetry and safety data will be performed for each patient in the study, to
      enable the Investigator to take a decision for the subsequent Lutathera doses. The results of
      dosimetry assessments (imaging and blood dosimetry) will be provided to the investigators for
      their evaluation prior to administration of subsequent therapeutic cycles in each patient.

      A total follow-up period of 5 years (60 months) after the last Lutathera dose will take place
      for each patient who received at least one dose of Lutathera. This follow-up period will be
      comprised of a short-term follow-up of 6 months to evaluate cumulative Lutathera toxicities,
      followed by a long-term follow up of another 54 months.

      An external Data and Safety Monitoring Board (DSMB) will also operate in the study to
      evaluate accumulating safety and dosimetry data, to ensure the safety of adolescents enrolled
      in the study, and to provide recommendations to investigators as well as to the clinical team
      in charge of conducting the study.
    

Trial Arms

NameTypeDescriptionInterventions
GEP-NET and PPGLExperimentalAll eligible participants will receive Lutathera (7.4 GBq/200 mCi x 4 administrations every 8 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.
  • Lutetium [177Lu] oxodotreotide/dotatate

Eligibility Criteria

        Key Inclusion Criteria:

          1. GEP-NET cohort: presence of metastasized or locally advanced, inoperable (curative
             intent), histologically proven, G1 or G2 (Ki-67 index =< 20%), well differentiated
             GEP-NET.

             or PPGL cohort: presence of metastasized or locally advanced, inoperable (curative
             intent), histologically proven PPGL.

          2. Patients from 12 to < 18 years of age at the time of enrollment.

          3. Expression of somatostatin receptors confirmed by a somatostatin receptor imaging
             (SRI) modality within 3 months prior to enrollment, with tumor uptake observed in the
             target lesions more or equal to the normal liver uptake.

          4. Performance status as determined by Karnofsky score >= 50 or Lansky Play-Performance
             Scale score >= 50.

          5. Parent's ability to understand and the willingness to sign a written informed consent
             document for adolescents as determined by local regulations. Adolescents will sign
             assent along with parental/legal guardian consent or will co-sign consent with
             parent/legal guardian in accordance with local regulation, prior to participation in
             the study.

        Key Exclusion Criteria:

          1. Laboratory parameters:

               1. Estimated creatinine clearance calculated by the Cockroft-Gault method < 70
                  mL/min

               2. Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x109/L; platelets <75x109/L.

               3. Total bilirubin >3 x ULN for age.

               4. Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.

          2. Established or suspected pregnancy.

          3. Breastfeeding female patients unless they accept to discontinue breastfeeding from the
             1st dose until 3 months after the last administration of study drug.

          4. Female patients of child-bearing potential, unless they are using highly effective
             methods of contraception during treatment and for 6 months after the last dose of
             Lutathera.

          5. Sexually active male patients, unless they agree to remain abstinent or be willing to
             use effective methods of contraception.

          6. Patients for whom in the opinion of the investigator other therapeutic options are
             considered more appropriate than the therapy offered in the study, based on patient
             and disease characteristics.

          7. Current spontaneous urinary incontinence.

          8. Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in
             situ of the uterine cervix, unless definitively treated and proven no evidence of
             recurrence for 5 years.

          9. Hypersensitivity to the study drug active substance or to any of the excipients.

         10. Patients with any other significant medical, psychiatric, or surgical condition,
             currently uncontrolled by treatment, which may interfere with the completion of the
             study.

         11. Patient with known incompatibility to CT Scans with I.V. contrast due to allergic
             reaction or renal insufficiency. If such a patient can be imaged with MRI, then the
             patient would not be excluded.

         12. Patients who received any investigational agent within the last 30 days.
      
Maximum Eligible Age:17 Years
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Absorbed radiation doses in target organ
Time Frame:Up to 8 days after the first lutetium Lu 177 dose
Safety Issue:
Description:Absorbed radiation doses in target organ (e.g. kidney and bone marrow) will be evaluated when all GEP-NET patients have completed the 1st treatment of Lutathera and completed the dosimetry assessment.

Secondary Outcome Measures

Measure:Incidence of adverse events (AEs) during the short-term follow-up
Time Frame:Up to 6 months after the last lutetium Lu 177 dose
Safety Issue:
Description:Cumulative safety of Lutathera in adolescents with SSTR-positive GEP-NETs will be assessed through the incidence of adverse events (AEs) and laboratory toxicities until 6 months after the last Lutathera dose.
Measure:Incidence of adverse events (AEs) during the long term follow-up
Time Frame:Up to 5 years after the last lutetium Lu 177 dose
Safety Issue:
Description:Long-term safety of Lutathera in adolescents with SSTR-positive GEP-NETs will be evaluated through the incidence of AEs and laboratory abnormalities during the 5-year follow-up after the last Lutathera dose.
Measure:Comparative assessment of organ absorbed doses in adolescents and adults
Time Frame:Up to 8 days after the first lutetium Lu 177 dose
Safety Issue:
Description:Calculated organ absorbed doses based on imaging radioactivity concentration data from adolescent with SSTR-positive GEP-NETs patients will be compared to the predicted distribution/organ absorbed doses in adult population.
Measure:Maximum plasma concentration (Cmax) of lutetium Lu 177 dotatate in adolescents and adults
Time Frame:Day 1 (0, 2, 6 hours post infusion), Day 2 (24 hours post infusion), Day 4 (72 hours post infusion)
Safety Issue:
Description:Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
Measure:Time of observed drug concentration occurrence (Tmax) of lutetium Lu 177 dotatate in adolescents and adults
Time Frame:Day 1 (0, 2, 6 hours post infusion), Day 2 (24 hours post infusion), Day 4 (72 hours post infusion)
Safety Issue:
Description:Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.
Measure:Area Under plasma concentration-time Curve from time 0 to 72 hours (AUC0-72) of lutetium Lu 177 dotatate in adolescents and adults
Time Frame:Day 1 (0, 2, 6 hours post infusion), Day 2 (24 hours post infusion), Day 4 (72 hours post infusion)
Safety Issue:
Description:Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC0-72 will be listed and summarized using descriptive statistics.
Measure:Total systemic clearance for intravenous administration (CL) of lutetium Lu 177 dotatate in adolescents and adults
Time Frame:Day 1 (0, 2, 6 hours post infusion), Day 2 (24 hours post infusion), Day 4 (72 hours post infusion)
Safety Issue:
Description:Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.
Measure:Volume of distribution in the central compartment (V1) of lutetium Lu 177 dotatate in adolescents and adults
Time Frame:Day 1 (0, 2, 6 hours post infusion), Day 2 (24 hours post infusion), Day 4 (72 hours post infusion)
Safety Issue:
Description:Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. V1 will be listed and summarized using descriptive statistics.
Measure:Volume of distribution in the peripheral compartment (V2) of lutetium Lu 177 dotatate in adolescents and adults
Time Frame:Day 1 (0, 2, 6 hours post infusion), Day 2 (24 hours post infusion), Day 4 (72 hours post infusion)
Safety Issue:
Description:Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. V2 will be listed and summarized using descriptive statistics.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Advanced Accelerator Applications

Trial Keywords

  • GEP-NET
  • PPGL
  • adolescents
  • pediatric
  • Lutathera
  • lutetium (177Lu) oxodotreotide
  • lutetium Lu 177 dotatate
  • PRRT

Last Updated

January 15, 2021