Efficacy of Everolimus Alone or in Combination With Pasireotide LAR in Advanced PNET

NCT01374451 | Terminated Phase 2 Results DMC

• 2 other identifiers: CSOM230I22012010-023183-40
• Study Type: interventional
• Target: 160
• Locations: 19 countries
• Sites: 47

Brief Summary

This study will estimate the treatment effect of everolimus in combination with pasireotide LAR relative to everolimus alone on progression-free survival (PFS) in patients with advanced progressive PNET. A planned primary analysis was completed with data cut of 02-Apr-2014. The study did not meet its primary objective, which was based on progression-free survival (PFS) as per local radiology assessment and was prematurely terminated with the last patient last visit on 19-Feb-2015. However, it is important to note that the data did not reveal any new safety concerns. It was decided to stop the study and this decision was shared with the study sites on 31-Jul-2014.

Conditions

Islet Cell Tumor

Keywords

Pancreatic; Neuroendocrine tumors; PNET; Pasireotide; Everolimus; Advanced progressive pancreatic neuroendocrine tumor

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) Per Local Radiological Review

  PFS per RECIST 1.0. (Response Evaluation Criteria in Solid Tumors). PFS was defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause.

  Once 80 PFS events had occurred aproximately after 24 months

Secondary Outcomes (11)

• Safety and Tolerability Profile of Everolimus Alone or in Combination With Pasireotide LAR

  Once 80 PFS events had occurred

• Objective Response Rate (ORR) as Per Radiology Review

  Once 80 PFS events had occurred

• Duration of Response (DoR)

  Once 80 PFS events had occurred

• Overall Survival (OS) Using Kaplan Meier Method

  Once 80 PFS events had occurred

• PFS and the Predictive Probability of Success in Phase III

  Once 105 PFS events had occurred occurred

Study Arms (2)

Paseriotide LAR + Everolimus

EXPERIMENTAL

everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im

Drug: Everolimus; Drug: Pasireotide LAR

Everolimus

EXPERIMENTAL

everolimus 10 mg once daily po alone

Drug: Everolimus

Interventions

Everolimus DRUG

Everolimus was supplied as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets

Also known as: RAD001

Everolimus; Paseriotide LAR + Everolimus

Pasireotide LAR DRUG

Pasireotide LAR intra-muscular depot injections were supplied as a powder in vials containing 20 mg and 40 mg with ampoules containing 2 mL of vehicle (for reconstitution).

Also known as: SOM230 LAR

Paseriotide LAR + Everolimus

Eligibility Criteria

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

You may qualify if:

• Advanced histologically confirmed well differentiated pancreatic neuroendocrine tumor
• Progressive disease within the last 12 months
• Measurable disease per RECIST Version 1.0 determined by multiphase MRI or triphasic CT

You may not qualify if:

• Patients currently requiring somatostatin analog treatment
• Prior therapy with mTOR inhibitors or pasireotide
• Patients with more than 2 prior systemic treatment regimens
• Previous cytotoxic chemotherapy, targeted therapy, somatostatin analogs, or biotherapy within the last 4 weeks

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (47)

Dana Farber Cancer Institute SC-2

Boston, Massachusetts, 02115, United States

Location

Montefiore Medical Center MMC

The Bronx, New York, 10467, United States

Location

Oregon Health & Science University Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

University of Texas/MD Anderson Cancer Center UT MD Anderson Cancer Ctr

Houston, Texas, 77030-4009, United States

Location

Novartis Investigative Site

Buenos Aires, Buenos Aires, C1264AAA, Argentina

Location

Novartis Investigative Site

Caba, Buenos Aires, C1426ANZ, Argentina

Location

Novartis Investigative Site

St Leonards, New South Wales, 2065, Australia

Location

Novartis Investigative Site

Herston, Queensland, 4029, Australia

Location

Novartis Investigative Site

Brussels, 1070, Belgium

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Ghent, 9000, Belgium

Location

Novartis Investigative Site

Haine-Saint-Paul, 7100, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 20230-130, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01246-000, Brazil

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H1T 2M4, Canada

Location

Novartis Investigative Site

Aarhus, 8000, Denmark

Location

Novartis Investigative Site

Copenhagen N, DK-2200, Denmark

Location

Novartis Investigative Site

Bordeaux, 33075, France

Location

Novartis Investigative Site

Clichy, 92110, France

Location

Novartis Investigative Site

Lyon, 69437, France

Location

Novartis Investigative Site

Marseille, 13385, France

Location

Novartis Investigative Site

Villejuif, 94805, France

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

München, 81675, Germany

Location

Novartis Investigative Site

Budapest, 1062, Hungary

Location

Novartis Investigative Site

Budapest, 1085, Hungary

Location

Novartis Investigative Site

Debrecen, 4032, Hungary

Location

Novartis Investigative Site

Bologna, BO, 40138, Italy

Location

Novartis Investigative Site

Milan, MI, 20141, Italy

Location

Novartis Investigative Site

Modena, MO, 41100, Italy

Location

Novartis Investigative Site

Fukuoka, Fukuoka, 812-8582, Japan

Location

Novartis Investigative Site

Rotterdam, 3015 CE, Netherlands

Location

Novartis Investigative Site

Grafton, Auckland, New Zealand

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Novartis Investigative Site

Madrid, Madrid, 28041, Spain

Location

Novartis Investigative Site

Lund, SE-221 85, Sweden

Location

Novartis Investigative Site

Uppsala, SE-751 85, Sweden

Location

Novartis Investigative Site

Bangkok, 10330, Thailand

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Ankara, Turkey, 06100, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, 34303, Turkey (Türkiye)

Location

Novartis Investigative Site

Cambridge, CB2 2QQ, United Kingdom

Location

Novartis Investigative Site

Glasgow, G12 0YN, United Kingdom

Location

Novartis Investigative Site

Manchester, M20 9BX, United Kingdom

Location

MeSH Terms

Conditions

Adenoma, Islet Cell; Neuroendocrine Tumors; Neuroectodermal Tumors, Primitive

Interventions

Everolimus

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; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasms, Neuroepithelial

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

A planned primary analysis was completed with data cut of 02-Apr-2014. The study did not meet its primary objective, which was based on progression-free survival as per local radiology assessment and was prematurely terminated.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: June 14, 2011
• First Posted: June 16, 2011
• Study Start: June 1, 2011
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: December 20, 2016
• Results First Posted: December 20, 2016

Record last verified: 2016-10

Locations

JP (1); IT (3); NL (1); ES (3); HU (3); US (4); SE (2); BE (5); DE (2); AU (2); NZ (1); TU (2); BR (2); CA (2); FR (5); GB (3); DK (2); TH (2); AR (2)