PRRT alone versus PRRT plus chemotherapy for gastroenteropancreatic neuroendocrine tumors

PReCedeNT Trial: Phase III Randomised Controlled Open Label Trial of Lutetium 177 PRRT Plus Chemotherapy Versus PRRT Aalone in FDG Avid Well Differentiated Gastroenteropancreatic Neuroendocrine Tumors

This test sees if adding capecitabine–temozolomide chemotherapy to Lutetium‑177 DOTATATE PRRT helps adults with advanced gastroenteropancreatic neuroendocrine tumors live longer without the cancer getting worse.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 162 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tata Memorial Hospital (other gov)
• Drugs / interventions: chemotherapy
• Locations: 2 sites (Mumbai, Maharashtra and 1 other locations)
• Trial ID: NCT07185672 on ClinicalTrials.gov

What this trial studies

This randomized Phase 3 trial compares standard peptide receptor radionuclide therapy (Lu‑177 DOTATATE) alone to Lu‑177 DOTATATE combined with capecitabine‑temozolomide chemotherapy in adults with gastroenteropancreatic neuroendocrine tumors (GEP‑NETs) who have somatostatin receptor–positive disease. Eligible tumors include well‑differentiated G1 (if recently progressed), G2 (Ki‑67 3–20%) and selected G3 (Ki‑67 up to 55%) cases, and require Ga‑68 DOTANOC PET Krenning score ≥3 and FDG PET positivity. Participants receive PRRT at study centers with scheduled imaging and lab monitoring to compare progression‑free survival, overall survival, and treatment‑related toxicity between the two arms. The trial is led by Tata Memorial Hospital with treatments delivered at Tata Memorial and ACTREC in the Mumbai/Navi Mumbai region of India.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed gastroenteropancreatic neuroendocrine tumors—well‑differentiated G2 (Ki‑67 3–20%) or selected G3 (Ki‑67 up to 55%), or progressing G1—with Ga‑68 DOTANOC Krenning score ≥3, FDG PET positivity, adequate organ function, ECOG ≤2 (or Karnofsky ≥60), and life expectancy >6 months are ideal candidates.

Not a fit: Patients with poor renal function (creatinine >1.6 mg/dL or creatinine clearance <50 mL/min), severe cytopenias or other major lab abnormalities, poor performance status, life expectancy under six months, or without somatostatin receptor–positive disease are unlikely to benefit or are excluded.

Why it matters

Potential benefit: If successful, adding capecitabine‑temozolomide to Lu‑177 PRRT could extend progression‑free survival and increase tumor response rates for patients with higher‑grade or FDG‑positive GEP‑NETs.

How similar studies have performed: Previous randomized trials (NETTER‑1 and NETTER‑2) established the benefit of Lu‑177 PRRT versus somatostatin analogs, while adding capecitabine–temozolomide to PRRT has shown encouraging results in smaller or retrospective series but has not been confirmed in a phase 3 setting.

Eligibility criteria

Inclusion Criteria:

* Male or female, age greater than 18 years
* Histopathological diagnosis of GEP-NET, necessarily satisfying all the the criteria below
* Well differentiated G2 (Ki67 : ≥3-20%) OR G3 (ki67- greater than 20-55%), OR
* Well-differentiated G1 (\<3%) with disease progression in last 6 months
* Positive Ga-68-DOTANOC PET/CT, Krennings score \>/=3
* Positive FDG PET imaging, grade 3 or 4 uptake
* Locally advanced/inoperable disease or metastatic disease
* Karnofsky performance-status score of at least 60 or ECOG performance status \</= 2
* Life expectancy greater than 6 months

Exclusion Criteria:

* Serum creatinine level of more than 1.6 mg/dl or a creatinine clearance of less than 50 ml/min
* Hemoglobin level of less than 8.0 g per deciliter
* Red blood cell count noty less than 300,000/cubic millimeter White cell count of less than 2000 per cubic millimeter
* Platelet count of less than 75,000 per cubic millimetre
* Total bilirubin level of more than 3 times the upper limit of the normal range
* Serum albumin level \< 3.0 g/dl
* Treatment with more than 30 mg of octreotide LAR within 4 weeks before randomisation.
* Peptide receptor radionuclide therapy at any time before randomisation
* Pregnancy and Lactation
* Patients with concurrent malignancies

Where this trial is running

Mumbai, Maharashtra and 1 other locations

• Tata Memorial Hospital, Mumbai, India — Mumbai, Maharashtra, India (RECRUITING)
• Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) — Navi Mumbai, Maharashtra, India (RECRUITING)

Study contacts

• Principal investigator: Ameya Puranik, MD — Professor and Consultant
• Study coordinator: Sushil K Yadav, MSc

Conditions: Neuroendocrine Neoplasia's, Neuroendocrine Tumor GEP Grade 1-3, Neuroendocrine Gastroenteropancreatic Tumour, Peptide Receptor Radionuclide Therapy, Lu-177 DOTATATE, PRRT, Neuroendocrine tumor, Capecitabine-Temozolamide