Combination External Radiation and PRRT for Large GI Neuroendocrine Tumors.

Not Applicable

Not yet recruiting

• Conditions: Digestive System Neuroendocrine Tumor; Unresectable Digestive System Neuroendocrine Neoplasm; Unresectable Digestive System Neuroendocrine Tumor G1; Unresectable Digestive System Neuroendocrine Tumor G2
• Interventions: Radiation: Stereotactic Body Radiation Therapy; Drug: Lutetium Lu 177 Dotatate; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Radiation: Gallium Ga 68-DOTATATE; Procedure: Positron Emission Tomography; Other: Questionnaire Administration

• Registration Number: NCT07150546
• Lead Sponsor: Emory University

Brief Summary

This phase I trial tests the safety and effectiveness of stereotactic body radiation therapy (SBRT) followed by 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in treating patients with large well-differentiated grade 1-2 digestive system neuroendocrine tumors that cannot be removed by surgery (unresectable). SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body. The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. 177Lu-DOTATATE is a radioactive drug. It binds to a protein called somatostatin receptor, which is found on some neuroendocrine tumor cells. 177Lu-DOTATATE builds up in these cells and gives off radiation that may kill them. It is a type of radioconjugate and a type of somatostatin analog. Giving PRRT after SBRT may reduce the chances of the disease returning or getting worse, compared to the standard treatment of PRRT alone.

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the rate of acute grade 3+ non-hematologic toxicity of PRRT after external radiation compared to historical control of PRRT alone.

SECONDARY OBJECTIVES:

I. To determine the rate of acute grade 2+ toxicity compared to historical control of PRRT alone.

II. To determine response rate of both large and small lesions at 3 months following treatment.

III. To determine progression free survival. IV. To describe patient-reported outcomes (PROs) of toxicity.

OUTLINE:

Patients undergo SBRT over 5 fractions in the absence of disease progression or unacceptable toxicity. Starting 4-10 weeks after completion of SBRT, patients receive standard of care (SOC) lutetium-177 DOTATATE (177Lu-DOTATATE) intravenously (IV) once every 8 weeks for 4 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and/or magnetic resonance imaging (MRI) throughout the trial and undergo gallium Ga 68-DOTATATE positron emission tomography (PET)/CT before treatment.

After completion of study treatment, patients are followed up at 90 days and then every 3 months for 12 months.

Study Timeline

• Status Verified: 2025-08
• Study First Submitted: 2025-08-25
• Study First Submitted QC: 2025-08-25
• Last Update Submitted: 2025-08-25
• Study Start: 2025-09-01
• Study First Posted: 2025-09-02
• Last Update Posted: 2025-09-02
• Primary Completion: 2025-09-30
• Study Completion: 2026-09-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Male or female
• Age ≥ 18 years
• Patient must be able to provide study specific informed consent
• Pathologically confirmed neuroendocrine tumor fulfilling all of the following criteria
• Well-differentiated, grade 1-2
• Unresectable (prior resection is allowable), verified by tumor board or surgical oncology (surg onc)
• Progression after one or two prior lines of systemic therapy
• Somatostatin-receptor positive disease as determined by positive radiotracer-labeled DOTATATE PET/CT scan (modified Krenning score 3+)
• One or more large lesions measuring 3 or more cm on contrast-enhanced CT or MRI
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Estimated glomerular filtration rate (GFR) > 30 mL/min (within 90 days prior to study registration)
• Total bilirubin ≤ 3 x upper limit of normal (within 90 days prior to study registration)
• Albumin > 30 g/L (within 90 days prior to study registration)
• White blood cell (WBC) ≥ 2,000 cells/mm^3 (within 90 days prior to study registration)
• Platelets ≥ 70000 cells/mm^3 (within 90 days prior to study registration)
• Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] ≥ 8.0 g/dl is acceptable.) (within 90 days prior to study registration)

Exclusion Criteria

• Any prior radiation therapy including prior PRRT, external radiation, or Yttrium-90 radioembolization to the same site/region
• Contraindications to radiation therapy including inflammatory bowel disease, systemic sclerosis, etc.
• Brain metastases or any metastases extending into the spinal canal
• Unable to obtain confirmation of payment coverage for any planned radiation treatment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (SBRT, 177Lu-DOTATATE)	Stereotactic Body Radiation Therapy	Patients undergo SBRT over 5 fractions in the absence of disease progression or unacceptable toxicity. Starting 4-10 weeks after completion of SBRT, patients receive SOC 177Lu-DOTATATE IV once every 8 weeks for 4 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI throughout the trial and undergo gallium Ga 68-DOTATATE PET/CT before treatment.
Treatment (SBRT, 177Lu-DOTATATE)	Lutetium Lu 177 Dotatate	Patients undergo SBRT over 5 fractions in the absence of disease progression or unacceptable toxicity. Starting 4-10 weeks after completion of SBRT, patients receive SOC 177Lu-DOTATATE IV once every 8 weeks for 4 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI throughout the trial and undergo gallium Ga 68-DOTATATE PET/CT before treatment.
Treatment (SBRT, 177Lu-DOTATATE)	Computed Tomography	Patients undergo SBRT over 5 fractions in the absence of disease progression or unacceptable toxicity. Starting 4-10 weeks after completion of SBRT, patients receive SOC 177Lu-DOTATATE IV once every 8 weeks for 4 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI throughout the trial and undergo gallium Ga 68-DOTATATE PET/CT before treatment.
Treatment (SBRT, 177Lu-DOTATATE)	Magnetic Resonance Imaging	Patients undergo SBRT over 5 fractions in the absence of disease progression or unacceptable toxicity. Starting 4-10 weeks after completion of SBRT, patients receive SOC 177Lu-DOTATATE IV once every 8 weeks for 4 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI throughout the trial and undergo gallium Ga 68-DOTATATE PET/CT before treatment.
Treatment (SBRT, 177Lu-DOTATATE)	Gallium Ga 68-DOTATATE	Patients undergo SBRT over 5 fractions in the absence of disease progression or unacceptable toxicity. Starting 4-10 weeks after completion of SBRT, patients receive SOC 177Lu-DOTATATE IV once every 8 weeks for 4 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI throughout the trial and undergo gallium Ga 68-DOTATATE PET/CT before treatment.
Treatment (SBRT, 177Lu-DOTATATE)	Positron Emission Tomography	Patients undergo SBRT over 5 fractions in the absence of disease progression or unacceptable toxicity. Starting 4-10 weeks after completion of SBRT, patients receive SOC 177Lu-DOTATATE IV once every 8 weeks for 4 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI throughout the trial and undergo gallium Ga 68-DOTATATE PET/CT before treatment.
Treatment (SBRT, 177Lu-DOTATATE)	Questionnaire Administration	Patients undergo SBRT over 5 fractions in the absence of disease progression or unacceptable toxicity. Starting 4-10 weeks after completion of SBRT, patients receive SOC 177Lu-DOTATATE IV once every 8 weeks for 4 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI throughout the trial and undergo gallium Ga 68-DOTATATE PET/CT before treatment.

Primary Outcome Measures

Name	Time	Method
Incidence of Acute Grade 3+ Non-Hematologic Adverse Events	Within 3 months of therapy	Will evaluate acute grade 3+ non-hematologic toxicity (based on Common Terminology Criteria for Adverse Events version 5) compared to historical controls of peptide receptor radionuclide therapy alone. The list of non-hematologic acute grade 3+ treatment related adverse events will be summarized descriptively using frequencies and percentages of all captured toxicities by severity and relevance. An exact binomial test will then be used to compare the observed toxicity rate to the historical control rate, assessing if the observed rate significantly exceeds expected levels.

Secondary Outcome Measures

Name	Time	Method
Incidence of Acute Grade 2+ Non-Hematologic Adverse Events	Up to 12 months	Non-hematologic acute grade 2+ treatment related adverse events will be summarized descriptively using frequencies and percentages of all captured toxicities by severity and relevance.
Response Rate	At 3 months	The response rate based on Response Evaluation Criteria in Solid Tumors criteria of both large and small lesions at 3 months following treatment will be calculated along with 95% exact confidence intervals.
Progression Free Survival	At 12 months	Progression free survival at 12 months will be estimated with the Kaplan-Meier method along with 95% confidence intervals.
Patient-Reported Health-Related Quality of Life	Up to 12 months	Patient reported outcome will be summarized as mean, median, first quartile, third quartile, and standard deviation.

Trial Locations

Locations (2)

Emory University Hospital Midtown; 🇺🇸 Atlanta, Georgia, United States

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States