An Open-label, Multi-center, Expanded Access Study of Everolimus in Participants With Advanced Neuroendocrine Tumors (NETs) (Core Study) and an Extension Study to the Open-label, Multi-center, Expanded Access Study of Everolimus in Patients With Advanced NETs (E1)

NCT01595009 | Completed Phase 4 Results

• 1 other identifier: CRAD001K24133
• Study Type: interventional
• Target: 246
• Locations: 1 country
• Sites: 11

Brief Summary

This record combines the results of CRAD001K24133 and CRAD001K24133E1. The purpose of the CRAD001K24133 study was to evaluate the safety profile of everolimus in patients with advanced neuroendocrine tumors of pancreatic origin (pNETs) and to provide access of everolimus to this patient population. Everolimus was taken by participants until disease progression, unacceptable toxicity, death, discontinuation from the trial for any other reason, or when it became commercially available for this indication, or until May 30, 2012, whichever came first. Prior to amendment 1, the study enrolled participants with NET of the lung (L-NETs) and gastrointestinal (GI) (GI-NETs) origin. The core study was stopped (per protocol) because everolimus was approved for pNETs. All ongoing patients with pNETs were switched to commercially available everolimus. For GI and lung NETs, everolimus was not approved at the time the core study was stopped. Therefore, patients with GI or lung NETs were not able to switch to commercial drug. To provide study medication access to these patients beyond 30 May 2012, the open label extension study, CRAD001K24133E1, was conducted. In the extension study, RAD001K24133E1, participants with GI or lung NETs who had not progressed during therapy with everolimus in the core study and who had not suffered from intolerable toxicity, were enrolled and treated with everolimus in order to provide data on long-term safety and efficacy. Patients were treated until it became commercially available in the respective indication or until documented tumor progression, unacceptable toxicity, any other reason or until study end on 31 May 2017, whichever came first.

Conditions

Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (2)

• Number and Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths (Core)

  The number of participants with AEs, SAEs and deaths were assessed.

  from the day of first treatment up to 19 months

• Number and Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths During the Extension Phase (E1)

  The number of participants with AEs, SAEs and deaths were assessed.

  from the first day of treatment in the extension up to 4 years

Secondary Outcomes (11)

• Investigator-assessed Progression Free Survival (PFS) (Core)

  from the day of first treatment up to 19 months

• Mean European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Score (Core)

  Baseline, weeks 4, 8, 20, 32, 44, and end of treatment (EOT) up to week 82

• Mean EORTC QLQ-G.I. NET21 Score (Core)

  Baseline, weeks 4, 8, 20, 32, 44, and end of treatment (EOT) up to week 82

• Number and Percentage of Participants With Ratings of 'no Problem, 'Some Problem' and 'Extreme Problem' in the EuroQol Five Dimensions Questionnaire (EQ-5D) (Core)

  Baseline, weeks 4, 8, 20, 32, 44, and end of treatment (EOT) up to week 82

• Mean EQ-5D Visual Analogue Scale (VAS) Score (Core)

  Baseline, weeks 4, 8, 20, 32, 44, and end of treatment (EOT) up to week 82

Study Arms (1)

Everolimus (RAD001)

EXPERIMENTAL

Participants received Everolimus 10 mg orally once daily until documented tumor progression, unacceptable toxicity or any other reason.

Drug: Everolimus (RAD001)

Interventions

Everolimus (RAD001) DRUG

Everolimus was supplied as tablets of 5mg strength.

Also known as: Afinitor

Everolimus (RAD001)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old
• Advanced (unresectable or metastatic) biopsy-proven NETs of pancreatic origin
• World health organization (WHO) Performance status of 0-2
• Adequate bone marrow function as shown by:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Hemoglobin \>9 g/dL
• Adequate liver function as shown by:
• Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 x ULN. Patients with known liver metastases with an AST and ALT ≤ 5 x ULN
• International normalized ratio (INR) \<1.3 (INR \<3 in patients treated with anticoagulants)
• Adequate renal function as shown by: Serum creatinine ≤ 1.5 x ULN
• Fasting serum cholesterol ≤ 300 mg/dL or ≤ 7.75 mmol/L and fasting triglycerides ≤ 2.5 x ULN
• Written informed consent obtained before any trial related activity and according to local guidelines.

You may not qualify if:

• Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma were not eligible.
• Following Amendment 1, patients with neuroendocrine tumors of GI or lung origin
• Cytotoxic chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to enrollment
• Hepatic artery embolization within the last two months or cryoablation or radiofrequency ablation of hepatic metastasis within two months of enrollment
• Prior therapy with mTOR inhibitors (for example sirolimus, temsirolimus, everolimus)
• Patients with a known hypersensitivity to everolimus or other rapamycin analogs (sirolimus, temsirolimus) or to its excipients
• Patients receiving chronic treatment with immunosuppressives
• Uncontrolled diabetes mellitus as defined by fasting serum glucose \>1.5 x ULN
• Patients who had any severe and/or uncontrolled medical conditions such as:
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction
• ≤ 6 months prior to enrollment, serious uncontrolled cardiac arrhythmia
• Active or uncontrolled severe infection
• A history of invasive fungal infections
• Severe hepatic impairment (Child Pugh class C)
• Severely impaired lung function

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (11)

Novartis Investigative Site

Berlin, 10098, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Chemnitz, 09113, Germany

Location

Novartis Investigative Site

Erlangen, 91054, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Homburg, 66421, Germany

Location

Novartis Investigative Site

Kassel, 34125, Germany

Location

Novartis Investigative Site

Mainz, 55131, Germany

Location

Novartis Investigative Site

München, 81377, Germany

Location

Novartis Investigative Site

Osnabrück, 49076, Germany

Location

Novartis Investigative Site

Weiden, 92637, Germany

Location

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

Everolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-1873

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 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2012
• First Posted: May 9, 2012
• Study Start: April 27, 2011
• Primary Completion: August 9, 2016
• Study Completion: August 9, 2016
• Last Updated: November 29, 2018
• Results First Posted: November 29, 2018

Record last verified: 2018-03

Locations

DE (11)