PRRT Versus PRRT Plus Chemotherapy in GEP NET (PReCedeNT Trial)

NCT07185672 | Recruiting Phase 3 DMC

• 1 other identifier: TMCIEC3258
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 2

Brief Summary

Neuroendocrine tumours (NETs), better defined as neoplasms (NENs), are a heterogeneous group of neoplasms that range from well-differentiated tumours to more aggressive carcinomas. Peptide receptor radionuclide therapy (PRRT) with Lutetium-177 DOTATATE is the established standard of care for patients with well-differentiated metastatic or locally advanced GEP-NETs. It has demonstrated a significant improvement in outcomes compared to Octreotide LAR, both as a first-line and second-line treatment approach, following the results of NETTER-1 and NETTER-2 trials, respectively. ENETS guidelines recommend the use of Ga-68 labeled DOTANOC/TOC/TATAE imaging only for WHO Grade 1 NET whereas FDG PET is the preferred modality for WHO Grade 3 NEN and NEC. For Grade 2 tumors (Mib index ranging from 3-20%), there are no strong recommendations for the addition of FDG PETCT in existing diagnostic algorithm. FDG PET positivity has been shown to be an independent predictor of shorter progression-free and overall survival in NET patients undergoing peptide receptor radionuclide therapy (PRRT). (8) Consequently, it is imperative to address FDG-avid tumors by integrating PRRT and chemotherapy. There are no strong recommendations for the grade wise management of GEP-NETs particularly grade 2 \& 3. Although recently published NETTER 2 trial substantiated the role of PRRT as a first line treatment for advanced grade GEP-NETs, still there is lack of evidence supporting the addition of chemotherapy in management of GEP-NETs. Given the absence of a prospective study to establish this treatment regimen, we designed a Phase 3 Randomized Controlled Trial to evaluate the combination of PRRT and CAPE-TEM-based chemotherapy in patients with FDG-positive metastatic well-differentiated NETs.

Conditions

Neuroendocrine Neoplasia's (NENs); Neuroendocrine Tumor GEP Grade 1-3; Neuroendocrine Gastroenteropancreatic Tumour

Keywords

Peptide Receptor Radionuclide Therapy; Lu-177 DOTATATE; PRRT; Neuroendocrine tumor; Capecitabine-Temozolamide

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression-free survival (PFS) will be defined as the time from enrolment to the time of disease progression or death, or to the date of last tumor assessment (until 36 months from last day of completion of treatment) without any such event (censored observation).

  From date of enrolment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months

Secondary Outcomes (2)

• Overall survival

  Time interval from enrolment to the date of death or last observation (censored), maximum until 24 months.

• Quality of Life parameters

  Day 1 of every treatment in both arms until treatment completion, and thereafter every 6 months upto 24 months

Study Arms (2)

Peptide Receptor Radionuclide Therapy with Lu177 DOTATATE

ACTIVE COMPARATOR

Patient in this arm will be treated only with 4 cycles of PRRT

Radiation: Peptide Receptor Radionuclide Therapy with Lu177 DOTATATE

PRRT with Lu-177 DOTATATE PLUS Capecitabine-Temozolamide

EXPERIMENTAL

Patient in this arm will be treated with combination of PRRT and Chemotherapy

Radiation: Peptide Receptor Radionuclide Therapy with Lu177 DOTATATE; Drug: Capecitabine plus temozolamide

Interventions

Peptide Receptor Radionuclide Therapy with Lu177 DOTATATE RADIATION

Radionuclide Therapy

Also known as: PRRT

PRRT with Lu-177 DOTATATE PLUS Capecitabine-Temozolamide; Peptide Receptor Radionuclide Therapy with Lu177 DOTATATE

Capecitabine plus temozolamide DRUG

Chemotherapy

Also known as: CAPE-TEM

PRRT with Lu-177 DOTATATE PLUS Capecitabine-Temozolamide

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tata Memorial Hospital: lead

Study Sites (2)

Tata Memorial Hospital, Mumbai, India

Mumbai, Maharashtra, 400012, India

RECRUITING

Advanced Centre for Treatment, Research and Education in Cancer (ACTREC)

Navi Mumbai, Maharashtra, 410210, India

RECRUITING

Related Publications (3)

• Parghane RV, Ostwal V, Ramaswamy A, Bhandare M, Chaudhari V, Talole S, Shrikhande SV, Basu S. Long-term outcome of "Sandwich" chemo-PRRT: a novel treatment strategy for metastatic neuroendocrine tumors with both FDG- and SSTR-avid aggressive disease. Eur J Nucl Med Mol Imaging. 2021 Mar;48(3):913-923. doi: 10.1007/s00259-020-05004-5. Epub 2020 Sep 2.

  PMID: 32876706 BACKGROUND

• Nicolini S, Bodei L, Bongiovanni A, Sansovini M, Grassi I, Ibrahim T, Monti M, Caroli P, Sarnelli A, Diano D, Di Iorio V, Grana CM, Cittanti C, Pieri F, Severi S, Paganelli G. Combined use of 177Lu-DOTATATE and metronomic capecitabine (Lu-X) in FDG-positive gastro-entero-pancreatic neuroendocrine tumors. Eur J Nucl Med Mol Imaging. 2021 Sep;48(10):3260-3267. doi: 10.1007/s00259-021-05236-z. Epub 2021 Feb 18.

  PMID: 33604690 BACKGROUND

• Puranik AD, Dev ID, Yadav S, Rangarajan V, Agrawal A, Basu S, Chaudhari VA, Ramaswamy A, Ostwal V, Bhandare MS, Shrikhande SV, Parghane RV, Bhargava P, Bal MM, Yadav S, Patkar S, Goel M, Purandare NC, Shah S, Choudhury S, Ghosh S, Venkatachalam M. PReCedeNT trial: Phase III randomized-controlled trial of Lutetium - 177 DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) plus Chemotherapy versus PRRT alone in FDG-avid, Well-differentiated Gastroenteropancreatic neuroendocrine tumors (GEP-NETs). BMC Cancer. 2025 Oct 28;25(1):1659. doi: 10.1186/s12885-025-15111-x.

  PMID: 41152774 DERIVED

Related Links

• Clinical Trial Registry of India

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Ameya Puranik, MD

  Professor and Consultant

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sushil K Yadav, MSc

CONTACT

912224177000; sushilyadav.crc@gmail.com

Farkhanda K Khan, MSc

CONTACT

912224177000; khanfarkhanda1998@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Phase 3 Open label Parallel Group Randomised Controlled Trial

Study Record Dates

• First Submitted: August 25, 2025
• First Posted: September 22, 2025
• Study Start: August 7, 2019
• Primary Completion (Estimated): August 7, 2027
• Study Completion (Estimated): August 7, 2027
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

IN (2)