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

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ClinicalTrials.gov Identifier: NCT03273712
Recruitment Status : Recruiting
First Posted : September 6, 2017
Last Update Posted : June 21, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sue O'Dorisio, University of Iowa

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

Condition or disease Intervention/treatment Phase
Neuroendocrine Tumors Meningioma Neuroblastoma Medulloblastoma Radiation: 90Y-DOTA tyr3-Octreotide Diagnostic Test: 68Ga-DOTATOC PET Positron Emission Tomography (PET) whole body scan Drug: Amino Acids Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 29, 2017
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020


Arm Intervention/treatment
Experimental: 90Y-DOTA-tyr3-Octreotide
Patients 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.
Radiation: 90Y-DOTA tyr3-Octreotide
90Y-DOTATOC is a radiopharmaceutical that will be used as a treatment for both children and adults with neuroendrocrine and other somatostatin receptor positive tumors.
Other Name: 90Y-DOTATOC

Diagnostic Test: 68Ga-DOTATOC PET Positron Emission Tomography (PET) whole body scan
68Ga-DOTATOC is a radiopharmaceutical used in PET scans to identify tumors as it can adhere to Somatostatin Receptors.

Drug: Amino Acids
This is a solution of amino acids that will decrease the amount of 90Y-DOTATOC that recirculates through the body after injection, therefore decreasing the radiation dose to the kidneys.
Other Name: Lysine and Arginine




Primary Outcome Measures :
  1. 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) occurring 6-9 months after treatment ]
    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.

  2. Renal, hematologic and clinical toxicities [ Time Frame: Initiation of treatment through last followup visit (6-9 months) after last treatment ]
    Adverse events will be recorded and reported in tabular form by type and grade. If four or more subjects experience renal toxicity ≥ Grade 4, the radiopharmaceutical will be declared too toxic and the trial will be stopped. If any other irreversible Grade 4 toxicity is observed in four or more subjects, the treatment will be declared too toxic and will be stopped. Adverse events will be graded according to the most recent CTE guidelines.


Secondary Outcome Measures :
  1. Accuracy of 68Ga-DOTATOC PET/CT in Participants [ Time Frame: 9 months ]
    Analyze accuracy of 68Ga-DOTATOC PET/CT to monitor response to PRRT after Cycle 1 and to evaluate overall response to PRRT. Change in metabolic activity (Standardized Uptake Value or SUV) in target lesions will be utilized to determine response to therapy using 1) SUVmax and 2) change in metabolic tumor burden and compared to RECIST criteria.

  2. Response to therapy of lesions identified by 68Ga-DOTATOC PET/CT [ Time Frame: 9 months ]
    For those subjects who participated in NCT01869725, determine response to therapy of lesions identified by 68Ga-DOTATOC PET/CT but not on Octreoscan as a confirmatory measure of true positives. The number, size, and location of discordant lesions between 68Ga-DOTATOC PET and Octreoscan will have been tabulated. This analysis will be updated using the results of post-therapy.

  3. Standard Uptake Value (SUV) on initial 68Ga-DOTATOC PET and SSTR2 expression [ Time Frame: 9 months ]
    Determine if Standard Uptake Value (SUV) on initial 68Ga-DOTATOC PET imaging correlates with SSTR2 expression as measured by quantitative messenger RNA (qPCR) or immunohistochemistry (IHC) on the diagnostic biopsy specimen. Compare SUVmax between primary tumor, liver lesions, and extra-hepatic lesions with expression levels of sst2 using qRT-PCR and/or receptor IHC from fresh frozen or paraffin-embedded samples where available.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 90 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 6 months 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.)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03273712


Contacts
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Contact: M. Sue O'Dorisio, MD, PhD 319-356-7873 sue-odorisio@uiowa.edu

Locations
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United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: M. Sue O'Dorisio, MD, PhD    319-356-7873    sue-odorisio@uiowa.edu   
Sponsors and Collaborators
Sue O'Dorisio
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Investigators
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Principal Investigator: M. Sue O'Dorisio, MD, PhD University of Iowa

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Responsible Party: Sue O'Dorisio, Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT03273712     History of Changes
Other Study ID Numbers: 201708778
R01CA167632 ( U.S. NIH Grant/Contract )
201412770 ( Other Identifier: University of Iowa )
First Posted: September 6, 2017    Key Record Dates
Last Update Posted: June 21, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Vascular Tissue
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neuroblastoma
Meningioma
Medulloblastoma
Nervous System Diseases
Glioma
Octreotide
Somatostatin
Edotreotide
Gastrointestinal Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Radiopharmaceuticals