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Theranostics: 68GaDOTATOC and 90YDOTATOC (PRRT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02441088
Recruitment Status : Active, not recruiting
First Posted : May 12, 2015
Last Update Posted : April 29, 2019
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sue O'Dorisio, University of Iowa

Brief Summary:

Participants in this research study have tumors that express somatostatin receptors such as neuroendocrine tumors, medulloblastoma, meningioma, and neuroblastoma.

Approximately 64 people will participate in this study conducted at the University of Iowa.

Condition or disease Intervention/treatment Phase
Neuroendocrine Tumors Carcinoid Tumors Neuroblastoma Medulloblastoma Drug: 90Y-DOTA-tyr3-Octreotide Radiation: Dosimetry-Guided Peptide Receptor Radiotherapy Drug: Aminosyn II Phase 2

Detailed Description:

Participants in this research study have tumors that express somatostatin receptors such as a neuroendocrine tumor, medulloblastoma, meningioma, and neuroblastoma.

The purpose of this research study is to determine if 90Y-DOTATOC is an effective treatment for tumors that express somatostatin receptors and if 68Ga-DOTATOC PET/CT can measure the extent of disease and measure response to this therapy. This research will determine if this process called dosimetry is an effective technique to determine how much 90Y-DOTATOC the participants can safely receive without damage to their kidneys and bone marrow.

Goals for this study are to:

  1. Demonstrate safety and efficacy of dosimetry-guided peptide receptor radiotherapy (PRRT) using 90Y-DOTA-tyr3-Octreotide (90Y-DOTATOC) 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) PET/CT as an accurate technique for diagnosis, staging, treatment targeting, and monitoring response to 90Y-DOTATOC therapy.

Approximately 64 people will participate in this study conducted at the University of Iowa.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dosimetry-Guided 90Y-DOTA-tyr3-Octreotide (90Y-DOTATOC) Peptide Receptor Radiotherapy (PRRT) in Children & Adults With Neuroendocrine and Other Somatostatin Receptor Expressing Tumors Determined by 68Ga-DOTA-tyr3-Octreotide (68Ga-DOTATOC) PET
Study Start Date : May 2015
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020

Arm Intervention/treatment
Experimental: PRRT with 90Y--DOTA-tyr3-Octreotide
A radiopharmaceutical, 90Y--DOTA-tyr3-Octreotide, and a renal protectant, Aminosyn II, in a dosimetry-guided theranostics trial for both children and adults with neuroendocrine and other somatostatin receptor positive tumors. Radiopharmaceutical will be administered IV in 3 doses, 6 weeks apart, with Aminosyn II administered concomittantly with each dose. Two followup visits are required at three and 6 months following third dose of 90Y-DOTA-tyr3-Octreotide.
Drug: 90Y-DOTA-tyr3-Octreotide
90Y-DOTATOC is a radiopharmaceutical that will be used in this a dosimetry-guided theranostics trial for both children and adults with neuroendocrine and other somatostatin receptor positive tumors. Each subject will receive three doses of 90Y-DOTATOC.
Other Name: 90Y-DOTATOC

Radiation: Dosimetry-Guided Peptide Receptor Radiotherapy
90Y-DOTATOC delivers radiation to rumor cells that express somatostatin receptors.The dose of 90Y-DOTATOC administered in this dosimetry-guided theranostics trial will be determined by dosimetry that estimates the amount of radiation delivered to the kidneys during treatments one and two.
Other Name: PRRT

Drug: Aminosyn II
Aminosyn II is a solution of amino acids that will decrease the amount of 90Y-DOTATOC that recirculates through the body after injection, therefore decreasing radiation dose to the kidneys.

Primary Outcome Measures :
  1. Tumor Response [ Time Frame: 9 months ]
    Response criteria according to RECIST 1.1. The method of Kaplan-Meier will be used to estimate progression and survival rates.

  2. Renal, hematologic, and clinical toxicities [ Time Frame: 9 months ]
    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 :
  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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   6 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 irradiated 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 craniospinal 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. Neuroendocrine archival tissue from a previous biopsy will be required.
  7. Age ≥ 6 months-100 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 with no greater than 1+ hematuria or proteinuria

    - Renal function* Adults (age 18 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 age

  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 long-acting somatostatin analogue in the past 28 days or long-acting lanreotide within the past 16 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 identifier (NCT number): NCT02441088

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United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
Sponsors and Collaborators
Sue O'Dorisio
National Institutes of Health (NIH)
National Cancer Institute (NCI)
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Principal Investigator: M S O'Dorisio, MD, PhD University of Iowa
  Study Documents (Full-Text)

Documents provided by Sue O'Dorisio, University of Iowa:

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Responsible Party: Sue O'Dorisio, Professor, Pediatrics and Hematology/Oncology, University of Iowa Identifier: NCT02441088    
Other Study ID Numbers: 201412770
R01CA167632 ( U.S. NIH Grant/Contract )
201708778 ( Other Identifier: University of Iowa )
First Posted: May 12, 2015    Key Record Dates
Last Update Posted: April 29, 2019
Last Verified: April 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
Carcinoid Tumor
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Amino-acid, glucose, and electrolyte solution
Gastrointestinal Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Parenteral Nutrition Solutions
Pharmaceutical Solutions