Stereotactic radiation followed by PRRT for large digestive neuroendocrine tumors

Combination External Radiation and 177Lu-DOTATATE for Large Gastrointestinal Neuroendocrine Tumors: A Single Arm Pilot Clinical Trial

This phase I trial tests whether giving focused external radiation (SBRT) followed by 177Lu‑DOTATATE (PRRT) is safe and helpful for adults with large, well‑differentiated grade 1–2 digestive system neuroendocrine tumors that cannot be removed by surgery.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Emory University (other)
• Drugs / interventions: radiation
• Locations: 2 sites (Atlanta, Georgia and 1 other locations)
• Trial ID: NCT07150546 on ClinicalTrials.gov

What this trial studies

This phase I study gives stereotactic body radiation therapy (SBRT) over five fractions to patients with large, well‑differentiated grade 1–2 digestive system neuroendocrine tumors, followed 4–10 weeks later by standard‑dose 177Lu‑DOTATATE every 8 weeks for four doses. Patients must have somatostatin‑receptor positive disease and at least one lesion ≥3 cm. The primary goal is to measure acute grade 3 or higher non‑hematologic toxicity of the combined approach compared with historical PRRT alone; secondary endpoints include grade 2+ toxicity, lesion response at 3 months, progression‑free survival, and patient‑reported toxicity. Imaging with CT, MRI and Ga‑68 DOTATATE PET/CT is used for staging and response assessment, and participants are followed for clinical outcomes and PROs for at least 12 months after treatment.

Who should consider this trial

Good fit: Adults (≥18) with pathologically confirmed, well‑differentiated grade 1–2, unresectable digestive system neuroendocrine tumors that are somatostatin‑receptor positive (Krenning score 3+), have one or more lesions ≥3 cm, have progressed after one or two prior systemic therapies, and have ECOG 0–2 with adequate organ function.

Not a fit: Patients with high‑grade neuroendocrine carcinoma, somatostatin‑receptor negative tumors, very poor performance status, inadequate renal or liver function, or who cannot receive SBRT/PRRT are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, this combined approach could improve local control of large unresectable digestive neuroendocrine tumors while keeping toxicity at an acceptable level.

How similar studies have performed: 177Lu‑DOTATATE (PRRT) alone has proven benefit in SSTR‑positive NETs, but combining SBRT with PRRT is a relatively novel strategy with limited prior clinical data.

Eligibility criteria

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

Where this trial is running

Atlanta, Georgia and 1 other locations

• Emory University Hospital Midtown — Atlanta, Georgia, United States (RECRUITING)
• Emory University Hospital — Atlanta, Georgia, United States (RECRUITING)

Study contacts

• Principal investigator: Pretesh Patel, MD — Emory University
• Study coordinator: Pretesh Patel, MD

Conditions: Digestive System Neuroendocrine Tumor, Unresectable Digestive System Neuroendocrine Neoplasm, Unresectable Digestive System Neuroendocrine Tumor G1, Unresectable Digestive System Neuroendocrine Tumor G2