Combination External Radiation and PRRT for Large GI Neuroendocrine Tumors.

Emory University

Status and phase

Not yet enrolling

Phase 1

Conditions

Unresectable Digestive System Neuroendocrine Tumor G2

Unresectable Digestive System Neuroendocrine Neoplasm

Digestive System Neuroendocrine Tumor

Unresectable Digestive System Neuroendocrine Tumor G1

Treatments

Radiation: Gallium Ga 68-DOTATATE

Procedure: Computed Tomography

Other: Questionnaire Administration

Procedure: Magnetic Resonance Imaging

Radiation: Stereotactic Body Radiation Therapy

Procedure: Positron Emission Tomography

Drug: Lutetium Lu 177 Dotatate

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT07150546

P30CA138292 (U.S. NIH Grant/Contract)

RAD6422-24 (Other Identifier)

STUDY00008681 (Other Identifier)

NCI-2025-05882 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

15 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

15 participants in 1 patient group

Treatment (SBRT, 177Lu-DOTATATE)

Experimental group

Description:

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.