Dosimetry Guided PRRT With 90Y-DOTATOC

NCT ID: NCT03013387

Last Updated: 2017-08-25

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2019-10-31

Brief Summary

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 the project are to

1. Demonstrate safety and efficacy of renal uptake 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.

Conditions

Neuroendrocrine Tumors; Meningioma; Neuroblastoma; Medulloblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PRRT with 90Y--DOTA-tyr3-Octreotide

The 90Y--DOTA-tyr3-Octreotide initial, Cycle 1 dose will be 50 mCi/m2 in children; 120 mCi in adults. Treatment consists of 3 cycles, 6-8 weeks apart. Cycle 1 dose is fixed. Cycles 2 and 3 doses will be determined by dosimetry-based calculation of renal doses from previous cycles; total renal dose ≤ 23Gy. 90Y-DOTA-tyr3-Octreotide will be administered with an amino acid solution to prevent radiation damage to kidneys. Amino acid infusion will begin 30 min prior to infusion of 90Y-DOTATOC and continue 3.5 hrs after infusion of study drugs.

68Ga-DOTATOC will be administered intravenously to perform the PET/CT scan. The dose will be 3-5 mCi (target 4mCi). The pediatric dose will be 0.043 mCi/kg with a minimum dose of 0.3 mCi and a maximum dose of 3 mCi in children <18 years old.

Group Type: EXPERIMENTAL

90Y-DOTA-3-tyr-Octreotide

Intervention Type: RADIATION

90Y-DOTATOC is a radiopharmaceutical that will be used l as a treatment for both children and adults with neuroendocrine and other somatostatin receptor positive tumors.

Positron Emission Tomography (PET) whole body scan

Intervention Type: PROCEDURE

68Ga-DOTATOC is a radiopharmaceutical used in PET scans to identify tumors as it can adhere to Somatostatin Receptors.

Amino Acids

Intervention Type: DRUG

This 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.

Interventions

90Y-DOTA-3-tyr-Octreotide

90Y-DOTATOC is a radiopharmaceutical that will be used l as a treatment for both children and adults with neuroendocrine and other somatostatin receptor positive tumors.

Intervention Type: RADIATION

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.

Intervention Type: PROCEDURE

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 radiation dose to the kidneys.

Intervention Type: DRUG

Other Intervention Names

90Y-DOTATOC; 68Ga-DOTATOC PET; Lysine and Arginine

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 (CT or MRI) and is determined to express somatostatin receptors by 68Ga-DOTATOC (TATE) PET within 120 days prior to entry into the trial.

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. 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,
• Renal function

• 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 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.)

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sue O'Dorisio

OTHER

Sponsor Role: lead

Responsible Party

Sue O'Dorisio

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

M S O'Dorisio, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Other Identifiers

1R01CA167632-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

201611818

Identifier Type: -

Identifier Source: org_study_id