887O - First multicentric randomized phase II trial investigating the antitumor efficacy of peptide receptor radionucleide therapy with ¹⁷⁷Lutetium-Octreotate (OCLU) in unresectable progressive neuroendocrine pancreatic tumor: Results of the OCLURANDOM trial

Background

No randomized trial has investigated the role of peptide receptor radionucleide therapy (PRRT) in advanced PanNET patients. We report the results of the first multicentric randomized open-label phase II study assessing PRRT-¹⁷⁷Lutetium-Octreotate antitumor efficacy.

Methods

Patients (pts) with somatostatin receptor scintigraphy positive progressive advanced PanNET within 1 year according to RECIST1.1 were randomized 1:1 to OCLU (7.4 GBqX4/8w) or sunitinib (SUN;37.5 mg/d ) and stratified for prognostic factors.Primary endpoint was: progression-free survival (PFS) rate at 12 months according to RECIST 1.1 real-time central review. Secondary endpoints were : tumour response, PFS, overall survival, safety (NCI CTCAE v.4). The sample size calculation of the OCLU arm assumed a 25% increase (from 35% to 60%) of the 12-m PFS rate. 40 pts had to be included in a single stage Fleming design with type I error = type II error = 5%. If 19 or more pts showed no progression or death at 12 months, OCLU would be considered effective (Fleming design conclusion). The SUN group served as an internal control to validate the hypothesis of the Fleming design with a 12 months PFS rate of 35%.

Results

84 pts were enrolled (41 OCLU arm , 43 SUN arm ;median age, 63 yrs,52% female). Main characteristics were:Ki67>10%, 37% pts; >25% liver involvement,42% pts; functioning syndrome, 20% pts ; ≥2 systemic lines, 43% , well balanced between each arm. The primary endpoint was met with a 12m-PFS rate at 80.5% (33/41 pts with 12m-PFS) in the OCLU arm (IC90%: 67.5-89.9) vs. 42 % in the SUN arm (n=18/43 pts with 12mPFS) (IC90%: 29.1-55.5,including 35%). Median PFS was 20.7 in the OCLU arm (90CI: 17.2-23.7) vs. 11 months in the SUN arm (90CI:8.8-12.4). 44% pts with OCLU vs. 60% with SUN experienced grade 3-4 adverse events, with fatigue (7% vs. 12%), decrease blood count (12% vs 24%) and hypertension (12% vs. 19%) among the most frequent. One death occurs in the SUN arm. Additional results will be presented (best response, updated adverse events and, subgroup analysis).

Conclusions

The OCLURANDOM trial met is primary endpoint.

Clinical trial identification

EudraCT 2013-004032-30.

Editorial acknowledgement

Legal entity responsible for the study

Gustave Roussy.

Funding

French Academic Projet Hospitalier Recherche Clinique (PHRC) grant and AAA/Novartis Pharma.

Disclosure

E. Baudin: Financial Interests, Institutional, Advisory Board, Advisory board and principal investigator: Novartis; Financial Interests, Institutional, Advisory Board: HRA, Hutchinson Pharma; Financial Interests, Personal, Other, Project lead and principal investigator: Ipsen; Financial Interests, Institutional, Other: Pfizer; Financial Interests, Personal, Advisory Board: Novartis - AAA; Financial Interests, Institutional, Research Grant: Novartis, HRA, Pfizer; Non-Financial Interests, Principal Investigator: Enterome; Non-Financial Interests, Advisory Role: Hutchinson Pharma; Non-Financial Interests, Leadership Role: Endocan Network. T.A. Walter: Financial Interests, Personal, Advisory Role: Novartis-AAA, Keocyt; Non-Financial Interests, Personal, Funding: Ipsen; Non-Financial Interests, Institutional, Project Lead: ROCHE. J. Hadoux: Financial Interests, Personal, Advisory Board: Ipsen, Lilly, Pharma Mar; Financial Interests, Institutional, Invited Speaker: AAA, Pfizer. C. Lachachi: Financial Interests, Institutional, Advisory Board: Novartis-AAA. D. Taieb: Financial Interests, Personal, Advisory Board: Novartis-AAA; Financial Interests, Personal, Invited Speaker: Novartis-AAA; Financial Interests, Institutional, Principal Investigator: Ipsen, Novartis-AAA. C. Ansquer: Financial Interests, Personal, Advisory Board: Novartis-AAA; Financial Interests, Personal, Invited Speaker: Novartis-AAA. L. de Mestier du Bourg: Financial Interests, Personal, Advisory Role: AAA, Ipsen, Keocyt, SIRTex. E. Deshayes: Financial Interests, Personal, Invited Speaker: Novartis-AAA. L. Dahan: Financial Interests, Personal, Invited Speaker: Servier, Novartis-AAA, Pierre Fabre, Oseus. Y. Touchefeu: Financial Interests, Personal, Invited Speaker: Novartis-AAA. C. Lombard Bohas: Financial Interests, Personal, Advisory Board: Novartis-AAA; Financial Interests, Institutional, Principal Investigator: Ipsen. All other authors have declared no conflicts of interest.