Dosimetry Guided PRRT With 90Y-DOTATOC
- Conditions
- Neuroendrocrine TumorsMeningiomaNeuroblastomaMedulloblastoma
- Interventions
- Radiation: 90Y-DOTA-3-tyr-OctreotideProcedure: Positron Emission Tomography (PET) whole body scan
- Registration Number
- NCT03013387
- Lead Sponsor
- Sue O'Dorisio
- 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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description PRRT with 90Y--DOTA-tyr3-Octreotide 90Y-DOTA-3-tyr-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. PRRT with 90Y--DOTA-tyr3-Octreotide Positron Emission Tomography (PET) whole body scan 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. PRRT with 90Y--DOTA-tyr3-Octreotide Amino Acids 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.
- Primary Outcome Measures
Name Time Method Treatment efficacy as assessed by change and defined as complete response, partial response or stable disease (CR+PR+SD) Lesions will be quantified and compared between pre-therapy and through follow-up visits: 1) occurring 3-4 months after treatment 3 and 2) occurring 6-9 months after treatment 3 Tumor response defined according to RECIST1.1 criteria applied on up to five target lesions (primary tumor, up to two: liver lesions, nodal metastases, and a metastatic lesion in other organs) 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. Enrollment will proceed according to an optimal Simon two-stage study design. Sixteen (16) enrolled in the first stage; if 7 or fewer patients respond, the arm will be closed and the treatment ruled clinically uninteresting. Otherwise, an additional 30 will be enrolled. If 24 or more responses are observed in the total of 46 subjects, then the treatment will be ruled worthy. The study design has a probability of early termination equal to 0.72. Power to detect efficacy is 0.80 with a type 1 error rate of 0.05.
Renal, hematologic, and clinical toxicities Lesions will be quantified and compared between pre-therapy and through follow-up visits: 1) occurring 3-4 months after treatment 3 and 2) occurring 6-9 months after treatment 3 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
Name Time Method Determine response to therapy of lesions identified by 68Ga-DOTATOC PET/CT but not identified on Octreoscan as a confirmatory measure of true positivity of the Ga-68 DOTATOC avid lesion Lesions will be quantified and compared between pre-therapy and through follow-up visits: 1) occurring 3-4 months after treatment 3 and 2) occurring 6-9 months after treatment 3 For subjects who participated in the 68Ga-DOTATOC Comparator trial (IRB # 201212736), the number, size, and location of discordant lesions between 68Ga-DOTATOC PET/CT and Octreoscan will have been tabulated. This analysis will be updated using the results of post- therapy 68Ga-DOTATOC PET/CT for those patients who participated in the comparator study, but only received the initial 68Ga-DOTATOC PET/CT due to progression on the Octreoscan + high-resolution, contrast-enhanced CT. Lesions that were positive on PET, but negative on Octreoscan will be considered true positive if a response to PRRT is documented after either Cycle 1 or at 6-9 month followup following last 90Y-DOTATOC infusion.
For subjects who did not participate in the 68Ga-DOTATOC Comparator trial, all 68Ga-DOTATOC PET/CT scans will be acquired as part of this study; number, size, and location of lesions will be analyzed between first and subsequent 68Ga-DOTATOC PET/CTs.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 Lesions will be quantified and compared between pre-therapy and through follow-up visits: 1) occurring 3-4 months after treatment 3 and 2) occurring 6-9 months after treatment 3 Compare maximum SUVs of primary tumor, liver lesions, and extra-hepatic lesions with expression level of sst2 RNA and IHC on fresh frozen tissue, or paraffin embedded samples (block(s) or 10 unstained slides) to determine whether or not any correlation exists between SUVmax, sst2 expression, or sst2 protein and response to PRRT. The study is expected to delineate whether measurement of sst2 expression by either qRT-PCT or immunohistochemistry at diagnosis can predict response to 90Y-DOTATOC. We will construct a table tabulating SUVmax, level of RNA expression, and IHC level for all lesions biopsied. With 64 subjects the correlation between SUV max, RNA expression and IHC will be determined. Analysis of SUVmax compared with sst2 RNA and receptor protein expression on primary tumor and metastatic lesions will be considered worthy of further study if \> 50% of lesions demonstrate a positive correlation.