Clinical Trials /

Dosimetry-Guided, Peptide Receptor Radiotherapy (PRRT) With 90Y-DOTA- tyr3-Octreotide (90Y-DOTATOC)

NCT03273712

Description:

This is a Phase 2 peptide receptor radionuclide therapy trial of 90Y-DOTATOC in patients with somatostatin receptor positive tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Dosimetry-Guided, Peptide Receptor Radiotherapy (PRRT) With 90Y-DOTA- tyr3-Octreotide (90Y-DOTATOC)
  • Official Title: Phase II, Dosimetry Guided, Peptide Receptor Radiotherapy (PRRT) Using 90Y-DOTA tyr3-Octreotide (90Y-DOTATOC) in Children and Adults With Neuroendocrine and Other Somatostatin Receptor Positive Tumors

Clinical Trial IDs

  • ORG STUDY ID: 201708778
  • SECONDARY ID: R01CA167632
  • SECONDARY ID: 201611818 (previous IRB#)
  • NCT ID: NCT03273712

Conditions

  • Neuroendocrine Tumors
  • Meningioma
  • Neuroblastoma
  • Medulloblastoma

Interventions

DrugSynonymsArms
Amino AcidsLysine and Arginine90Y-DOTA-tyr3-Octreotide

Purpose

This is a Phase 2 peptide receptor radionuclide therapy trial of 90Y-DOTATOC in patients with somatostatin receptor positive tumors.

Detailed Description

      This is a Phase 2 peptide receptor radionuclide therapy trial of 90Y-DOTATOC in patients with
      somatostatin receptor positive tumors. The somatostatin receptor targeting of the therapeutic
      will be checked with 68Ga-DOTATOC PET-CT imaging prior to therapy. Treatment consists of 3
      cycles, 6-8 weeks apart. Cycle 1 dose is fixed with Cycles 2 and 3 doses to be determined by
      dosimetry-based calculation of renal doses from previous cycles not to exceed 23 Gy for the
      total renal dose.

      The goals of this project are to

        1. Demonstrate the safety and efficacy of dosimetry-guided peptide receptor radiotherapy
           using 90Y-DOTA-tyr3-Octreotide in patients with neuroendocrine and other somatostatin
           receptor expressing tumors.

        2. Monitor all adverse events associated with peptide receptor radiotherapy using
           90Y-DOTATOC.

        3. Establish 68Ga-DOTA-tyr3-Octreotide (68Ga-DOTATOC) or 68Ga-DOTATATE PET/CT as an
           accurate technique for diagnosis, staging, treatment targeting, and monitoring response
           to 90Y-DOTATOC therapy.
    

Trial Arms

NameTypeDescriptionInterventions
90Y-DOTA-tyr3-OctreotideExperimentalPatients will receive 3 doses of 90YDOTATOC followed by 90Y-DOTATOC PET scans, with 6 -8 weeks between doses. They will be followed for 6-9 months after the last treatment dose. CT or MRI scans will be given at the 3 month and 6-9 month followups plus a 68Ga-DOTATOC or DOTATATE PET scan at the 6-9 month followup. The exact dose of 90YDOTATOC therapy for each patient will be determined by dosimetry.
  • Amino Acids

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. Participation in Iowa Neuroendocrine Tumor Registry.

          3. A pathologically confirmed (histology or cytology) malignant neoplasm with at least
             one target lesion that is confirmed by conventional imaging and is determined to
             express somatostatin receptors by 68Ga-DOTATOC (TATE) PET within 120 days prior to
             treatment with 90Y-DOTATOC.

          4. The target lesion is one that either has never received external beam radiation or has
             been previously irradiated and has since demonstrated progression. Any local
             irradiation of the target lesion or any non-target lesions via external beam,
             conformal or stereotactic radiation treatments must have occurred more than 4 weeks
             prior to study drug administration. Any full cranial-spinal radiation, whether or not
             a target lesion is included in the field, must have occurred more than 3 months prior
             to study drug administration.

          5. Life expectancy > 2 months at the time of study drug administration.

          6. Archival tissue from a previous biopsy will be required.

          7. Age ≥ 6 months-90 years at the time of study drug administration.

          8. Performance status as determined by Karnofsky ≥ 60 or Lansky Play Scale ≥ 60% at the
             time of study drug administration.

          9. Completion of Norfolk Quality of Life Questionnaire.

         10. Within 7-10 days of study drug administration, patients must have normal organ and
             marrow function as defined below:

               -  absolute neutrophil count >1000/mm3

               -  Platelets >90,000/mm3

               -  total bilirubin <3X ULN for age

               -  AST(SGOT) & ALT(SGPT) <10X institutional upper limit of normal for age

               -  Urinalysis no greater than 1+ hematuria or proteinuria

               -  Renal function* Adults(age18 or >): Serum creatinine ≤ 1.2 mg/dl; if serum
                  creatinine is >1.2 mg/dL, nuclear GFR will be measured. GFR will need to be ≥ 80
                  ml/min/1.73m2 for subjects ≤40 years old, ≥ 70 ml/min/1.73m2 for subjects between
                  41-50; ≥ 60 ml/min/1.73m2 for subjects between 51-60; ≥ 50 ml/min/1.73m2 for
                  subjects > 60 years old.

             Children(age <18): nuclear GFR ≥ 80 mL/min/1.73 m2

             * Renal function criteria based on our previous experience with 90Y-DOTATOC therapy
             and known changes in GFR with age13,21,33-35

         11. The effects of 90Y-DOTA-tyr3-Octreotide on the developing human fetus are unknown. For
             this reason and because Class C agents are known to be teratogenic, women and men of
             child-bearing potential must agree to use adequate contraception (hormonal or barrier
             method of birth control) prior to study entry and for the duration of study
             participation. Should a woman become pregnant or suspect she is pregnant while
             participating in this study, she should inform her treating physician immediately.

         12. Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          1. Pregnant women are excluded from this study because 90Y-DOTATOC is a Class C agent
             with potential teratogenic or abortifacient effects.

          2. Because there is an unknown but potential risk for adverse events in nursing infants
             secondary to treatment of the mother with 90Y-DOTATOC, breastfeeding should be
             discontinued until 6 weeks after the last administration of study drug.

          3. Surgery within 4 weeks of study drug administration.

          4. 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).

          5. Prior PRRT with 90Y-DOTATOC (TATE) or 177Lu-DOTATOC (TATE) or 131I-MIBG therapy for
             this malignancy.

          6. Another investigational drug within 4 weeks of study drug administration.

          7. Concurrent, malignant disease for which patient is on active therapy.

          8. 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.

          9. Any subject for whom, in the opinion of their physician, a 12-hour discontinuation of
             somatostatin analogue therapy represents a health risk. Also subjects who have
             received SandostatinLAR in the past 28 days or long-acting lanreotide within the past
             8 weeks are excluded. Subjects may be maintained on short acting octreotide during the
             time from last injection of long-acting somatostatin analogue until 12 hrs prior to
             injection of study drug. Known antibodies to Octreotide, Lanreotide, or DOTATOC or
             history of allergic reactions attributed to compounds of similar chemical or biologic
             composition to 90Y-DOTATOC.

         10. Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or
             mitomycin C) of study drug administration or those who have not recovered from adverse
             events due to agents administered more than 4 weeks earlier.

         11. Uncontrolled illness including, but not limited to ongoing or active infection,
             symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or
             psychiatric illness/social situations that would limit compliance with study
             requirements.

         12. Subject weighs more than 450 pounds. (Subjects who weigh more than 450 pounds will not
             be able to fit inside the imaging machines.)

         13. Inability to lie still for the entire imaging time (due to cough, severe arthritis,
             etc.)
      
Maximum Eligible Age:90 Years
Minimum Eligible Age:6 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Treatment efficacy as assessed by change and defined as complete response, partial response or stable disease (CR+PR+SD)
Time Frame:Lesions will be quantified and compared between pre-therapy and through follow-up visits: 1) occuring 3-4 months after treatment and 2) occuring 6-9 months after treatment
Safety Issue:
Description:Tumor response defined by RECIST1.1 criteria applied on up to five target lesions (primary tumor if not surgically removed, up to two liver lesions, up to two nodal metastases, metastatic lesion in other organs, such as ovary, breast) that will be quantified and compared between pre-therapy and 3-9 months post-therapy high-resolution, contrast-enhanced CTs. 90Y DOTATOC will be deemed worthy of further study if its associated response rate is ≥ 0.60, and clinically uninteresting if its rate is ≤ 0.40.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sue O'Dorisio

Last Updated

October 1, 2017