Study to Evaluate the Safety of Combining Two Radionuclide Therapies to Treat Mid-gut Neuroendocrine Tumors

NCT03044977 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: 201608857P50CA174521-02
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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. Currently, the safest and best tolerated doses of these drugs (when combined together) is unknown.

Conditions

Neuroendocrine Tumor, Malignant; Neuroendocrine Tumor Gastrointestinal, Hormone-Secreting

Keywords

3-Iodobenzylguanidine; dose-response relationship, radiation; theranostic; radionuclide; MIBG; DOTA

Outcome Measures

Primary Outcomes (4)

• glomular filtration rate (eGFR)

  Evaluate renal toxicity using eGFR measurement

  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

  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

  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

  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)

  Every 6 months for up to 5 years

• Overall survival (OS)

  Up to 5 years

Study Arms (8)

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)

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)

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)

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.

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.

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.

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.

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.

Drug: 90Y-DOTA-3-Tyr-Octreotide; Drug: 131I-MIBG

Interventions

90Y-DOTA-3-Tyr-Octreotide DRUG

Peptide receptor radiotherapy (PRRT) using Yttrium-90 as the active radionuclide. For intravenous administration only.

Also known as: 90Y DOTATOC

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-MIBG DRUG

Peptide receptor radiotherapy (PRRT) using Iodine-131 as the active radionuclide. For intravenous administration only.

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)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• ≥ 18 to 70 years at the time of study drug administration.
• Karnofsky Performance Status at least 70%
• Agrees to contraception.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• David Bushnell: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator
• Holden Comprehensive Cancer Center: collaborator

Study Sites (1)

Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Related Publications (2)

• 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.

  PMID: 26116109 BACKGROUND

• Madsen 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.

  PMID: 16595501 BACKGROUND

Related Links

• The website describing the Specialized Programs of Research Excellence in Neuroendocrine Cancers that supports this clinical trial.

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

90Y-octreotide, DOTA-Tyr(3)-; 3-Iodobenzylguanidine

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Iodobenzenes; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Hydrocarbons, Iodinated; Hydrocarbons, Halogenated

Study Officials

• David Bushnell, MD

  University of Iowa

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: dose-escalation design

Study Record Dates

• First Submitted: February 2, 2017
• First Posted: February 7, 2017
• Study Start: May 7, 2017
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2027
• Last Updated: August 16, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Typically, after completion of study
• Access Criteria: A data sharing agreement will need to be filed for sharing the individual participant data. A contract may be required.

Locations

US (1)