Antitumor Efficacy of Peptide Receptor Radionuclide Therapy With 177Lutetium -Octreotate Randomized vs Sunitinib in Unresectable Progressive Well-differentiated Neuroendocrine Pancreatic Tumor: First Randomized Phase II

NCT02230176 | Completed Phase 2

• 2 other identifiers: 2013-004032-302013/2043
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

This study is the first randomized, open-label, national, multicenter, phase II study assessing the efficacy and safety of OCLU in subjects with pretreated progressive pancreatic, inoperable, somatostatin receptor positive, well differentiated pancreatic neuroendocrine tumors (WDpNET). Subjects must have experienced documented progression of disease within 1 year prior to the start of the study. The control group of patients receiving Sutent will be used as internal control to assess the hypothesis of 12 months PFS equal to 35% in patients receiving Sutent.

Conditions

Pancreatic Neuroendocrine Carcinoma

Outcome Measures

Primary Outcomes (1)

• To determine the 12 months PFS

  Assessed 12 months after randomization

Secondary Outcomes (2)

• Overall Survival

  Assessed every 3 months until death

• Best response

  Assessed every 12 weeks until progression up to 48 months

Study Arms (2)

177Lu-DOTA0-Tyr3-Octreotate or OCLU

EXPERIMENTAL

7.4 GBq per injection (max: 4 injections)

Drug: 177Lu-DOTA0-Tyr3-Octreotate

Sunitinib

ACTIVE COMPARATOR

37.5 mg/day

Drug: Sunitinib

Interventions

Sunitinib DRUG

Sunitinib

177Lu-DOTA0-Tyr3-Octreotate DRUG

177Lu-DOTA0-Tyr3-Octreotate or OCLU

Eligibility Criteria

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

You may qualify if:

• Histologically proven and reviewed well differentiated malignant pancreatic sporadic NET Metastatic disease not amenable to surgical resection
• All target lesions (lesions measurable and non-measurable according to the RECIST 1.1 criteria), of a size ≥ 15 mm, twice the spatial resolution of the somatostatin receptor scintigraphy (SRS), should be positive (grade of uptake at SRS≥ 2, equal to the physiologic liver uptake) within 24 weeks prior to enrollment. Negative target lesions are acceptable if below 15mm.
• Post first line whatever the type of systemic therapy: cytotoxic chemotherapy or everolimus or somatostatine analogs… Only one line of cytotoxic chemotherapy is authorized.
• Evaluable disease according to RECIST 1.1 criteria (Appendix 2)
• Progressing disease within 12 months prior to randomization according to RECIST 1.1 criteria ;
• ECOG performance status 0-2 (appendix 9)
• Life expectancy ≥ 6 months as prognosticated by the physician
• Age ≥ 18 years, no superior limit
• Adequate bone marrow reserve (Hb \> 8, neutrophils ≥ 1500/mm³ and platelets ≥80.000/mm\^3)
• Effective contraception in pre-menopausal female and male patients during and for at least 6 months post-treatment.
• Patient´s signed written informed consent
• Ability to comply with the protocol procedures
• Ability to take oral medication
• Patient affiliated to a social security system or beneficiary of the same.

You may not qualify if:

• Large or small cell-poorly differentiated pancreatic neuroendocrine tumor according to WHO 2010 classification
• More than one line of cytotoxic chemotherapy (a patient who received the same molecules of cytotoxic chemotherapy at several times during therapeutic management is considered to have benefit from one single line of cytotoxic chemotherapy)
• Prior external beam radiation therapy to more than 25% of the bone marrow
• Urinary incontinence
• History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least five years.
• Severe renal (measured GFR according to MDRD \<50ml/mn or nephrotic syndrome) or hepatic insufficiency (ALT / AST \> 2.5 x ULN or ALT/AST \>5 x ULN if liver function abnormalities are due to the underlying malignancy and/or total serum bilirubin \> 2.5 x ULN)
• Serum albumin \<3.0 g/dL unless prothrombin time is within the normal range.
• Uncontrolled diabetes mellitus as defined by a fasting blood glucose above 2 ULN
• Decompensated heart failure (ejection fraction \<45%), myocardial infarction, stroke, pulmonary embolism or revascularization procedure,unstable angina pectoris, uncontrolled cardiac arrhythmia, and clinically significant bradycardia during the last 12 months.
• Hypertension that cannot be controlled despite medications (\>=160/95 mmHg despite optimal medical therapy)
• Abnormal cardiac function with 12 lead ECG. Ongoing cardiac dysrhythmias of NCI CTC grade 2, atrial fibrillation of any grade, or prolongation of the QTc interval to \>470 msec for males or \>480 msec for females.
• Brain metastases (unless these metastases have been treated and stabilized for at least 24 weeks, prior to enrolment in the study. Patients with a history of brain metastases must have a head CTscan with contrast or MRI to document stable disease prior to enrolment in the study.)
• Pregnancy or breast feeding (see appendix 6)
• Previous treatment with the drugs under study. Prior systemic treatment with any tyrosine kinase inhibitors or anti-VEGF angiogenic inhibitors.
• Current treatment with another investigational drug.

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead
• National Cancer Institute, France: collaborator
• Advanced Accelerator Applications: collaborator

Study Sites (1)

Gustave Roussy

Villejuif, Val De Marne, 94805, France

Location

MeSH Terms

Conditions

Somatostatinoma

Interventions

Sunitinib; lutetium Lu 177 dotatate

Condition Hierarchy (Ancestors)

Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Carcinoma, Islet Cell; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Eric BAUDIN, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 27, 2014
• First Posted: September 3, 2014
• Study Start: February 1, 2015
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: April 20, 2025

Record last verified: 2025-04

Locations

FR (1)