Neuroendocrine Tumor, MalignantEarly Phase 1NCT03044977
Study to Evaluate the Safety of Combining Two Radionuclide Therapies to Treat Mid-gut Neuroendocrine Tumors
A Early Phase 1 study testing 90Y-DOTA-3-Tyr-Octreotide and 131I-MIBG in people with Neuroendocrine Tumor, Malignant and Neuroendocrine Tumor Gastrointestinal, Hormone-Secreting, run by David Bushnell at 1 site in United States.
Trial summary
This study is designed to identify the best tolerated doses of [131]Iodine-MIBG and [90]Yttrium-DOTATOC when co-administered to treat midgut neuroendocrine tumors. These drugs (131I-MIBG, 90Y-DOTATOC) are radioactive drugs, known as radionuclide therapy. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Neuroendocrine Tumor, Malignant, Neuroendocrine Tumor Gastrointestinal, Hormone-Secreting
- What is being tested?
- 90Y-DOTA-3-Tyr-Octreotide and 131I-MIBG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 7 May 2017to Dec 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to understand and the willingness to provide informed consent.
- A pathologically confirmed (histology or cytology) malignant neoplasm that is determined to be well-differentiated neuroendocrine tumor (i.e. grade 1 or grade 2). The primary tumor location should be known or believed to be midgut, or pheochromocytoma, or paraganglioma.
- Disease not amenable to curative intent treatment (primarily surgery) and in addition has shown either clinical or radiographic progression on all available (non-radionuclidic) therapies known to confer clinical benefit.
- SSTR positive sites as demonstrated by either SSTR2 positivity (2+ or 3+ intensity and greater than 10% tumor cell occupying the receptors) or a nuclear medicine scan utilizing 111In-DTPA-Phe3-Octreotide (Octreoscan™) or 68Ga-DOTA-tyr3-Octreotide within 12 months prior to anticipated C1D1 demonstrating SSTR positive tumor sites
- ≥1 tumor site must have demonstrated uptake equal to or greater than normal liver as documented by nuclear scan imaging
- ≥1 evaluable site of disease measuring ≥ 1.5 cm in diameter on CT or MRI as measured per RECIST
Show all 19Show fewer
- ≥ 18 to 70 years at the time of study drug administration.
- Karnofsky Performance Status at least 70%
- Agrees to contraception.
- Subjects must demonstrate at least one of the following:
- One or more MIBG+ and DOTATOC- tumors in addition to one or more DOTATOC+ tumors, and/or,
- One or more tumor sites where the calculated "safe" radiation tumor dose is higher by at least 25% with a combination of 131I-MIBG and 90Y-DOTATOC than it is with 90Y DOTATOC alone, or,
- Within 2 weeks of study drug administration for therapeutic intent, patients must have normal organ and marrow function as defined below:
- absolute neutrophil count ≥ 2000 cells/mm3
- platelets ≥100,000 cells/mm3
- total bilirubin <1.5 x institutional ULN for age and weight
- AST(SGOT) ≤ 2.5 x institutional ULN
- ALT (SGPT) ≤ 2.5 x institutional ULN
- eGFR ≥ 50 mL/min/1.73 m2 (Cockroft Gault formula)
Who cannot join
- Patients who are considered a fall risk.
- Women who are pregnant or breast feeding.
- Surgery, radiation or chemotherapy within 4 weeks of proposed step 1 start date.
- Prior peptide-receptor radiotherapy (PRRT).
- Investigational drug within 4 weeks of proposed step 1 start date.
- More than one concurrent, malignant disease.
Show all 17Show fewer
- History of congestive heart failure and cardiac ejection fraction ≤ 40%.
- Patients for whom, in the opinion of their physician, a 24-hour discontinuation of somatostatin analogue therapy represents a health risk.
- Patients who are unable to discontinue medications known to affect MIBG uptake
- Proteinuria, grade 2 (i.e., ≥ 2+proteinuria).
- Long-acting somatostatin analogue treatment within 14 days of proposed step 1 start date.
- Prior external beam radiation involving kidneys (scatter doses of < 500 cGy to a single kidney or radiation to < 50% of a single kidney is acceptable).
- Prior external beam radiation (including brachytherapy) involving 25% of bone marrow (excluding scatter doses of ≤ 5 Gy).
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to 90Y-DOTA-tyr3-Octreotide, Octreoscan®, 68Ga-Octreotide, or 131I-MIBG.
- Uncontrolled intercurrent 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.
- If a subject meets STEP 1 criteria, a serial SPECT scan is performed for dosimetry. Step 2 criteria must be met and verified prior to therapy initiation.
- STEP 2:
Trial locations and contacts
1 site in 1 country.
United States1 site
Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
About this study
Official title: Phase 1 Trial Using 131I MIBG and 90Y DOTATOC in a Dosimetrically Determined Optimal Combination for Therapy of Selected Patients With Midgut Neuroendocrine Tumors.
This study is designed to identify the best tolerated doses of [131]Iodine-MIBG and [90]Yttrium-DOTATOC when co-administered to treat midgut neuroendocrine tumors. These drugs (131I-MIBG, 90Y-DOTATOC) are radioactive drugs, known as radionuclide therapy. Currently, the safest and best tolerated doses of these drugs (when combined together) is unknown.
Read the detailed description
[131]Iodine-MIBG and [90]Yttrium-DOTATOC are radioactive drugs designed to treat specific tumor cells. These drugs are a combination of the radiation (131-Iodine, 90-Yttrium) and a protein that targets the tumor cell (MIBG or DOTATOC). Because these proteins are attracted to, and stick to, the tumor, the radiation is centered in the tumors. This kills more tumor cells and minimizes radiation-damage to healthy tissues, like the heart and lungs.
Two organs still absorb some of the radiation, though: bone marrow and the kidney. These organs limit how much radiation can be given to tumors, but we don't know how much radiation is too much. Too much radiation to bone marrow can result in anemia. Too much radiation to the kidneys can result in kidney failure. From prior radiation therapies, we have a general idea of how much radiation we can give safely.
131I-MIBG and 90Y-DOTATOC have never been given together. We want to give them together because many times, tumors are actually groups of different types of cells. This means, not all the cells respond to therapy the same way. If some tumor cells survive therapy, the tumor will continue to grow and eventually come back. We know some mid-gut neuroendocrine tumors (NETs) have targets for DOTATOC and some other mid-gut NETs have targets for MIBG. We also have now identified that some people with mid-gut NETs have different tumors: some with targets for MIBG and some with targets for DOTATOC. For these people, this means treating only with 131I-MIBG or 90Y-DOTATOC will not be enough to treat their cancer. They need both radioactive drugs.
Because we are combining these radioactive drugs, this study is known as a first-in-man study. We are also using a special imaging to help us estimate the radiation dose to the bone marrow and to the kidneys. This is what decides the final dose of 131I-MIBG and 90Y-DOTATOC.
Before receiving therapy, participants will be asked to undergo imaging to verify they have both MIBG and DOTATOC tumor types:
- participants are given very small doses of radioactive drugs
- a special camera (SPECT/CT) collects images (scans)
- imaging (scans) are done over 3 calendar days
- blood samples are taken at that time, too, to measure the circulating amount of tracer doses
If the scans show a participant has both MIBG and DOTATOC tumors, therapy is given:
- a customized dose of 90Y-DOTATOC is given on day 1 of a treatment cycle. This is given outpatient.
- a customized dose of 131I-MIBG is given on day 2 of a treatment cycle. This is given inpatient (admitted to the hospital).
- participants are monitored through blood tests to identify the side effects of therapy.
Each participant can have up to 2 cycles of therapy. The cycles are 12 weeks apart.
The doses for 90Y-DOTATOC and 131I-MIBG are decided based on radiation to the bone marrow and radiation to the kidney. Doses are decided by how well other participants have done on this study.
Participants have life long follow-up for this study. This is very important, because a study like this has not been done.
- Being tested
- 90Y-DOTA-3-Tyr-Octreotide, 131I-MIBG
- Keywords
- 3-Iodobenzylguanidine, dose-response relationship, radiation, theranostic, radionuclide, MIBG, DOTA
- Medical subject headings
- Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
90Y-DOTA-3-Tyr-OctreotideDrug
Also called 90Y DOTATOC
Peptide receptor radiotherapy (PRRT) using Yttrium-90 as the active radionuclide. For intravenous administration only.
131I-MIBGDrug
Peptide receptor radiotherapy (PRRT) using Iodine-131 as the active radionuclide. For intravenous administration only.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | This is the initial treatment arm. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart.
Radiation exposure to the bone marrow is limited to 150 centiGray (cGy) Radiation exposure to the kidneys is limited to 1900 centiGray (cGy) Receives: Drug: 90Y-DOTA-3-Tyr-Octreotide; Drug: 131I-MIBG |
| Cohort 2 | Experimental | This treatment arm is opened if Cohort 1 is successful. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart.
Radiation exposure to the bone marrow is limited to 200 centiGray (cGy) Radiation exposure to the kidneys is limited to 2300 centiGray (cGy) Receives: Drug: 90Y-DOTA-3-Tyr-Octreotide; Drug: 131I-MIBG |
| Cohort 3 | Experimental | This treatment arm is opened if Cohort 2 is successful. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart.
Radiation exposure to the bone marrow is limited to 250 centiGray (cGy) Radiation exposure to the kidneys is limited to 2300 centiGray (cGy) Receives: Drug: 90Y-DOTA-3-Tyr-Octreotide; Drug: 131I-MIBG |
| Cohort -1 (alternative cohort) | Experimental | This treatment arm is opened if Cohort 1 is not tolerated.
131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart.
Radiation exposure to the bone marrow is limited to 100 centiGray (cGy) Radiation exposure to the kidneys is limited to 1500 centiGray (cGy)
No further dose evaluations are done after this cohort is completed. Receives: Drug: 90Y-DOTA-3-Tyr-Octreotide; Drug: 131I-MIBG |
| Cohort 2.1 (renal alternative) | Experimental | This treatment arm is opened if the kidney radiation exposure was not tolerated in cohort 2.
131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart.
Radiation exposure to the bone marrow is limited to 200 centiGray (cGy) Radiation exposure to the kidneys is limited to 1500 centiGray (cGy)
No further dose evaluations are done after this cohort is completed. Receives: Drug: 90Y-DOTA-3-Tyr-Octreotide; Drug: 131I-MIBG |
| Cohort 2.2 (bone marrow alternative) | Experimental | This treatment arm is opened if the kidney radiation exposure was not tolerated in cohort 2.
131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart.
Radiation exposure to the bone marrow is limited to 100 centiGray (cGy) Radiation exposure to the kidneys is limited to 2300 centiGray (cGy)
No further dose evaluations are done after this cohort is completed. Receives: Drug: 90Y-DOTA-3-Tyr-Octreotide; Drug: 131I-MIBG |
| Cohort 3.1 (renal alternative) | Experimental | This treatment arm is opened if the kidney radiation exposure was not tolerated in cohort 3.
131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart.
Radiation exposure to the bone marrow is limited to 250 centiGray (cGy) Radiation exposure to the kidneys is limited to 1900 centiGray (cGy)
No further dose evaluations are done after this cohort is completed. Receives: Drug: 90Y-DOTA-3-Tyr-Octreotide; Drug: 131I-MIBG |
| Cohort 3.2 (bone marrow alternative) | Experimental | This treatment arm is opened if the kidney radiation exposure was not tolerated in cohort 2.
131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart.
Radiation exposure to the bone marrow is limited to 150 centiGray (cGy) Radiation exposure to the kidneys is limited to 2300 centiGray (cGy)
No further dose evaluations are done after this cohort is completed. Receives: Drug: 90Y-DOTA-3-Tyr-Octreotide; Drug: 131I-MIBG |
What is being measured
The primary outcome is the main question the study is designed to answer.
glomular filtration rate (eGFR)
Evaluate renal toxicity using eGFR measurement
Measured: 4 and 8 weeks after each treatment, then at 3, 6, & 9 months after the last treatment
urine protein
Evaluate renal toxicity using urine protein measurement
Measured: Monthly beginning 4 weeks after the first treatment through 6 months after the last treatment
platelet count decreased
Evaluate bone marrow toxicity using platelet counts
Measured: Weeks 4, 5, 6, 7, 8 after each therapy and then 3, 6, & 12 months after the last treatment
absolute neutrophil count decreased
Evaluate bone marrow toxicity using absolute neutrophil count
Measured: Weeks 4, 5, 6, 7, 8 after each therapy and then 3, 6, & 12 months after the last treatment
Secondary outcomes (2)
Progression free survival (PFS)
From day 1 of therapy to documented disease progression in CT or MRI as per RECIST criteria
Measured: Every 6 months for up to 5 years
Overall survival (OS)
From start of treatment (cycle 1, day 1) until the date of death from any cause.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2017 (estimated)
- Study start7 May 2017
- Primary completionDec 2025 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Neuroendocrine Tumor, MalignantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- dose-escalation design
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- David Bushnell
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI), Holden Comprehensive Cancer Center
- Responsible party
- Sponsor-investigator, David Bushnell, University of Iowa
- Investigators
- David Bushnell, MD, Study chair, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03044977
- Sponsor's protocol ID
- 201608857
- Other IDs
- P50CA174521-02
- Status last verified
- Aug 2023
- First submitted
- 2 Feb 2017
- Last updated
- 16 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Information will be distributed via clinicaltrials.gov and shared as per the filed NIH data sharing plan
Publications
Bushnell DL, Madsen MT, O'cdorisio T, Menda Y, Muzahir S, Ryan R, O'dorisio MS. Feasibility and advantage of adding (131)I-MIBG to (90)Y-DOTATOC for treatment of patients with advanced stage neuroendocrine tumors. EJNMMI Res. 2014 Dec;4(1):38. doi: 10.1186/s13550-014-0038-2. Epub 2014 Sep 10.
PubMed 26116109Madsen MT, Bushnell DL, Juweid ME, Menda Y, O'Dorisio MS, O'Dorisio T, Besse IM. Potential increased tumor-dose delivery with combined 131I-MIBG and 90Y-DOTATOC treatment in neuroendocrine tumors: a theoretic model. J Nucl Med. 2006 Apr;47(4):660-7.
PubMed 16595501
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Trial Using 131I MIBG and 90Y DOTATOC in a Dosimetrically Determined Optimal Combination for Therapy of Selected Patients With Midgut Neuroendocrine Tumors.
- ClinicalTrials.gov ID
- NCT03044977
- Acronym / sponsor ID
- 201608857
- Keywords
- 3-Iodobenzylguanidine, dose-response relationship, radiation, theranostic, radionuclide, MIBG, DOTA
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- David BushnellUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI), Holden Comprehensive Cancer Center
- Study start
- 7 May 2017 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 7 Feb 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to identify the best tolerated doses of [131]Iodine-MIBG and [90]Yttrium-DOTATOC when co-administered to treat midgut neuroendocrine tumors. These drugs (131I-MIBG, 90Y-DOTATOC) are radioactive drugs, known as radionuclide therapy. Currently, the safest and best tolerated doses of these drugs (when combined together) is unknown.
Detailed description
[131]Iodine-MIBG and [90]Yttrium-DOTATOC are radioactive drugs designed to treat specific tumor cells. These drugs are a combination of the radiation (131-Iodine, 90-Yttrium) and a protein that targets the tumor cell (MIBG or DOTATOC). Because these proteins are attracted to, and stick to, the tumor, the radiation is centered in the tumors. This kills more tumor cells and minimizes radiation-damage to healthy tissues, like the heart and lungs.
Two organs still absorb some of the radiation, though: bone marrow and the kidney. These organs limit how much radiation can be given to tumors, but we don't know how much radiation is too much. Too much radiation to bone marrow can result in anemia. Too much radiation to the kidneys can result in kidney failure. From prior radiation therapies, we have a general idea of how much radiation we can give safely.
131I-MIBG and 90Y-DOTATOC have never been given together. We want to give them together because many times, tumors are actually groups of different types of cells. This means, not all the cells respond to therapy the same way. If some tumor cells survive therapy, the tumor will continue to grow and eventually come back. We know some mid-gut neuroendocrine tumors (NETs) have targets for DOTATOC and some other mid-gut NETs have targets for MIBG. We also have now identified that some people with mid-gut NETs have different tumors: some with targets for MIBG and some with targets for DOTATOC. For these people, this means treating only with 131I-MIBG or 90Y-DOTATOC will not be enough to treat their cancer. They need both radioactive drugs.
Because we are combining these radioactive drugs, this study is known as a first-in-man study. We are also using a special imaging to help us estimate the radiation dose to the bone marrow and to the kidneys. This is what decides the final dose of 131I-MIBG and 90Y-DOTATOC.
Before receiving therapy, participants will be asked to undergo imaging to verify they have both MIBG and DOTATOC tumor types:
- participants are given very small doses of radioactive drugs
- a special camera (SPECT/CT) collects images (scans)
- imaging (scans) are done over 3 calendar days
- blood samples are taken at that time, too, to measure the circulating amount of tracer doses
If the scans show a participant has both MIBG and DOTATOC tumors, therapy is given:
- a customized dose of 90Y-DOTATOC is given on day 1 of a treatment cycle. This is given outpatient.
- a customized dose of 131I-MIBG is given on day 2 of a treatment cycle. This is given inpatient (admitted to the hospital).
- participants are monitored through blood tests to identify the side effects of therapy.
Each participant can have up to 2 cycles of therapy. The cycles are 12 weeks apart.
The doses for 90Y-DOTATOC and 131I-MIBG are decided based on radiation to the bone marrow and radiation to the kidney. Doses are decided by how well other participants have done on this study.
Participants have life long follow-up for this study. This is very important, because a study like this has not been done.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 8
- Model description
- dose-escalation design
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: 90Y-DOTA-3-Tyr-Octreotide, Drug: 131I-MIBGThis is the initial treatment arm. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart. Radiation exposure to the bone marrow is limited to 150 centiGray (cGy) Radiation exposure to the kidneys is limited to 1900 centiGray (cGy) |
| Cohort 2 | Experimental | Drug: 90Y-DOTA-3-Tyr-Octreotide, Drug: 131I-MIBGThis treatment arm is opened if Cohort 1 is successful. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart. Radiation exposure to the bone marrow is limited to 200 centiGray (cGy) Radiation exposure to the kidneys is limited to 2300 centiGray (cGy) |
| Cohort 3 | Experimental | Drug: 90Y-DOTA-3-Tyr-Octreotide, Drug: 131I-MIBGThis treatment arm is opened if Cohort 2 is successful. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart. Radiation exposure to the bone marrow is limited to 250 centiGray (cGy) Radiation exposure to the kidneys is limited to 2300 centiGray (cGy) |
| Cohort -1 (alternative cohort) | Experimental | Drug: 90Y-DOTA-3-Tyr-Octreotide, Drug: 131I-MIBGThis treatment arm is opened if Cohort 1 is not tolerated. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart. Radiation exposure to the bone marrow is limited to 100 centiGray (cGy) Radiation exposure to the kidneys is limited to 1500 centiGray (cGy) No further dose evaluations are done after this cohort is completed. |
| Cohort 2.1 (renal alternative) | Experimental | Drug: 90Y-DOTA-3-Tyr-Octreotide, Drug: 131I-MIBGThis treatment arm is opened if the kidney radiation exposure was not tolerated in cohort 2. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart. Radiation exposure to the bone marrow is limited to 200 centiGray (cGy) Radiation exposure to the kidneys is limited to 1500 centiGray (cGy) No further dose evaluations are done after this cohort is completed. |
| Cohort 2.2 (bone marrow alternative) | Experimental | Drug: 90Y-DOTA-3-Tyr-Octreotide, Drug: 131I-MIBGThis treatment arm is opened if the kidney radiation exposure was not tolerated in cohort 2. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart. Radiation exposure to the bone marrow is limited to 100 centiGray (cGy) Radiation exposure to the kidneys is limited to 2300 centiGray (cGy) No further dose evaluations are done after this cohort is completed. |
| Cohort 3.1 (renal alternative) | Experimental | Drug: 90Y-DOTA-3-Tyr-Octreotide, Drug: 131I-MIBGThis treatment arm is opened if the kidney radiation exposure was not tolerated in cohort 3. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart. Radiation exposure to the bone marrow is limited to 250 centiGray (cGy) Radiation exposure to the kidneys is limited to 1900 centiGray (cGy) No further dose evaluations are done after this cohort is completed. |
| Cohort 3.2 (bone marrow alternative) | Experimental | Drug: 90Y-DOTA-3-Tyr-Octreotide, Drug: 131I-MIBGThis treatment arm is opened if the kidney radiation exposure was not tolerated in cohort 2. 131I-MIBG and 90Y-DOTATOC are administered once per cycle, for up to 2 cycles 12 weeks apart. Radiation exposure to the bone marrow is limited to 150 centiGray (cGy) Radiation exposure to the kidneys is limited to 2300 centiGray (cGy) No further dose evaluations are done after this cohort is completed. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Ability to understand and the willingness to provide informed consent.
- A pathologically confirmed (histology or cytology) malignant neoplasm that is determined to be well-differentiated neuroendocrine tumor (i.e. grade 1 or grade 2). The primary tumor location should be known or believed to be midgut, or pheochromocytoma, or paraganglioma.
- Disease not amenable to curative intent treatment (primarily surgery) and in addition has shown either clinical or radiographic progression on all available (non-radionuclidic) therapies known to confer clinical benefit.
- SSTR positive sites as demonstrated by either SSTR2 positivity (2+ or 3+ intensity and greater than 10% tumor cell occupying the receptors) or a nuclear medicine scan utilizing 111In-DTPA-Phe3-Octreotide (Octreoscan™) or 68Ga-DOTA-tyr3-Octreotide within 12 months prior to anticipated C1D1 demonstrating SSTR positive tumor sites
- ≥1 tumor site must have demonstrated uptake equal to or greater than normal liver as documented by nuclear scan imaging
Key exclusion criteria (17 listed)
- Patients who are considered a fall risk.
- Women who are pregnant or breast feeding.
- Surgery, radiation or chemotherapy within 4 weeks of proposed step 1 start date.
- Prior peptide-receptor radiotherapy (PRRT).
- Investigational drug within 4 weeks of proposed step 1 start date.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 90Y-DOTA-3-Tyr-OctreotideAlso: 90Y DOTATOCPeptide receptor radiotherapy (PRRT) using Yttrium-90 as the active radionuclide. For intravenous administration only. | Drug | Cohort -1 (alternative cohort), Cohort 1, Cohort 2, Cohort 2.1 (renal alternative), Cohort 2.2 (bone marrow alternative), Cohort 3, Cohort 3.1 (renal alternative), Cohort 3.2 (bone marrow alternative) |
| 131I-MIBGPeptide receptor radiotherapy (PRRT) using Iodine-131 as the active radionuclide. For intravenous administration only. | Drug | Cohort -1 (alternative cohort), Cohort 1, Cohort 2, Cohort 2.1 (renal alternative), Cohort 2.2 (bone marrow alternative), Cohort 3, Cohort 3.1 (renal alternative), Cohort 3.2 (bone marrow alternative) |
Primary outcome
glomular filtration rate (eGFR)
Time frame: 4 and 8 weeks after each treatment, then at 3, 6, & 9 months after the last treatment
Evaluate renal toxicity using eGFR measurement
urine protein
Time frame: Monthly beginning 4 weeks after the first treatment through 6 months after the last treatment
Evaluate renal toxicity using urine protein measurement
platelet count decreased
Time frame: Weeks 4, 5, 6, 7, 8 after each therapy and then 3, 6, & 12 months after the last treatment
Evaluate bone marrow toxicity using platelet counts
absolute neutrophil count decreased
Time frame: Weeks 4, 5, 6, 7, 8 after each therapy and then 3, 6, & 12 months after the last treatment
Evaluate bone marrow toxicity using absolute neutrophil count
2 secondary outcomes
Progression free survival (PFS)
Time frame: Every 6 months for up to 5 years
Overall survival (OS)
Time frame: Up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2023.
- Background: PubMed 26116109Bushnell DL, Madsen MT, O'cdorisio T, Menda Y, Muzahir S, Ryan R, O'dorisio MS. Feasibility and advantage of adding (131)I-MIBG to (90)Y-DOTATOC for treatment of patients with advanced stage neuroendocrine tumors. EJNMMI Res. 2014 Dec;4(1):38. doi: 10.1186/s13550-014-0038-2. Epub 2014 Sep 10.
- Background: PubMed 16595501Madsen MT, Bushnell DL, Juweid ME, Menda Y, O'Dorisio MS, O'Dorisio T, Besse IM. Potential increased tumor-dose delivery with combined 131I-MIBG and 90Y-DOTATOC treatment in neuroendocrine tumors: a theoretic model. J Nucl Med. 2006 Apr;47(4):660-7.
- The website describing the Specialized Programs of Research Excellence in Neuroendocrine Cancers that supports this clinical trial.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Information will be distributed via clinicaltrials.gov and shared as per the filed NIH data sharing plan
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Bushnell, MD study chair
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing 90Y-DOTA-3-Tyr-Octreotide and 131I-MIBG in people with Neuroendocrine Tumor, Malignant and Neuroendocrine Tumor Gastrointestinal, Hormone-Secreting, run by David Bushnell at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 16 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
glomular filtration rate (eGFR) (time frame: 4 and 8 weeks after each treatment, then at 3, 6, & 9 months after the last treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03044977, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2023.