Neoadjuvant PRRT With Y-90-DOTATOC in pNET

NCT05568017 | Terminated Phase 2

• 1 other identifier: IEO 906
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Neuroendocrine tumors (NETs) are relatively rare tumors, mainly originating from the digestive system, that tend to be slow growing and are often diagnosed when metastatic. Surgery is the sole curative option, but is feasible only in a minority of patients. Peptide Receptor Radionuclide Therapy (PRRT) has been experimented for almost 20 years and is an established effective therapeutic modality for well/moderately differentiated, inoperable or metastasized gastro-entero-pancreatic (GEP) and bronchial NETs. Clinical studies demonstrated that partial and complete objective responses can be obtained in up to 30% of patients. Side effects may involve the kidneys and the bone marrow and are usually mild. Renal protection is used to minimize the risk of a late decrease of renal function. A new application for P-NETs is preoperative PRRT. Since surgery is the only curative option for GEPNETs, preoperative PRRT could increase the efficacy of surgery. However, this modality has not been fully explored in dedicated studies and there are just few sporadic case reports that described the preoperative use of PRRT in pancreatic NETs who could then be operated on successfully. Moreover there are few experiences demonstrating the advantage of PRRT associated to surgery in a multidisciplinary setting. In addition, the possibility of detecting the circulating NET transcripts by means of transcriptome analysis could represent an early marker of response to PRRT and improve the patient management. Aim of this study is to evaluate the response and rate of R0 surgery in patients with unresectable or borderline resectable PNETs eligible to PRRT with 90Y-DOTATOC and correlate the response to the variation in circulating NET transcripts measured before and after the end of PRRT. It has been recently shown that a PCR-based 51 transcript signature is significantly more sensitive and efficient than single analytes (e.g. CgA) in NET diagnosis and follow up. 30 patients will be enrolled in the study; each of them will receive 1.85 GBq/cycle of 90Y-DOTATOC with a cumulative activity of 9.25-11.1 GBq in 5-6 cycles (depending on personalized dosimetry). Therapy response will be assessed by morphological (CT/MRI) and functional (PET/CT or Octreoscan) imaging after 3 and 6 months from the completion of PRRT and compared with transcript analysis. Based on literature reports we expect a response rate of about 35% of patients.

Conditions

Pancreatic Neuroendocrine Tumor

Outcome Measures

Primary Outcomes (2)

• objective response evaluation

  objective responses (partial and complete responses, stable disease) will be evaluated according to modified RECIST criteria (mRECIST).

  3 months after end of PRRT

• objective response evaluation

  objective responses (partial and complete responses, stable disease) will be evaluated according to modified RECIST criteria (mRECIST).

  6 months after end of PRRT

Secondary Outcomes (3)

• rate of operability

  3 months after the end of PRRT.

• rate of operability

  3 months after the end of PRRT.

• analysis of tumor specific circulating NET transcripts

  before PRRT, and 3 and 6 months after therapy.

Study Arms (1)

Y-90-DOTATOC

EXPERIMENTAL

Patients will receive PRRT with Y-90-DOTATOC

Drug: peptide receptor radionuclide therapy with Y-90-DOTATOC

Interventions

peptide receptor radionuclide therapy with Y-90-DOTATOC DRUG

Patients with unresectable or borderline resectable pNETs will recive PRRT with 90Y-DOTATOC

Also known as: PRRT, Y-90-DOTATOC

Y-90-DOTATOC

Eligibility Criteria

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

You may qualify if:

• Patients affected by unresectable or borderline resectable P-NETs and limited liver disease
• Multidisciplinary evaluation in which a global therapy approach is proposed with PRRT in a neoadjuvant setting.
• Histopathologic diagnosis of WHO G1/G2 P-NET
• Conserved hematological, liver and renal parameters: hemoglobin \>/= 10 g/dL, absolute neutrophil count (ANC) \>/= 1.5 x 109 /L, platelets \>/= 100 x 109 /L, bilirubin \</= 1.5 X UNL (upper normal limit), ALT \< 2.5 X UNL (\< 5 X UNL in presence of liver metastases), creatinine \< 2 mg/dL.
• Age more than 18 years.
• Patients with documented disease will be admitted to therapeutic phase only if the diagnostic receptor imaging (Ga-68-peptides PET/CT or OctreoScan) demonstrate a significant uptake in the tumor (grade 2 or 3, according to a preset scoring, where grade 1= equal to normal liver, grade2 = higher than normal liver, grade 3= higher than kidneys and spleen), that may allow delivering a low absorbed dose to normal organs and a high dose to the tumor \[Cremonesi 1999, Cremonesi 2010\].
• Disease must be measurable by means of conventional imaging (CT or MRI)
• Before treatment clinical history data will be collected, physical examination will be performed and diagnostic and laboratory data will be examined.
• Patients must not receive other treatments (e.g. chemo- or radiotherapy) from one month before to two months after the completion of 90Y-DOTATOC cycles.
• Patients must be naive from previous radionuclide treatments with radiopeptides (e.g. 111Inpentetreotide, Lu-177-petides) or other radiopharmaceuticals (e.s. 131I-MIBG, 131I).

You may not qualify if:

• \- Pregnancy/breastfeeding (a pregnancy test not older than 7 days is mandatory).
• Assessed bone marrow invasion \> 25%.
• Other concomitant neoplasm (excluding in situ basaliomas and radically treated cervical cancers).
• ECOG score higher than 2.
• Expectancy of life shorter than 6 months.
• Patients with psycho-physical conditions that are not suitable for entering this clinical study and fulfilling its requirements.
• No multidisciplinary indication to surgery after PRRT

Sponsors & Collaborators

• European Institute of Oncology: lead
• Agenzia Italiana del Farmaco: collaborator

Study Sites (1)

Chiara Maria Grana

Milan, 20141, Italy

Location

MeSH Terms

Conditions

Adenoma, Islet Cell

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients affected by unresectable or borderline resectable P-NETs and limited liver disease will be enrolled

Study Record Dates

• First Submitted: September 23, 2022
• First Posted: October 5, 2022
• Study Start: September 15, 2020
• Primary Completion: September 23, 2022
• Study Completion: November 11, 2024
• Last Updated: November 20, 2024

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)