Overview

This trial is active, not recruiting.

Conditions advanced net of gi origin, advanced net of lung origin, neuroendocrine tumors
Treatments everolimus, everolimus placebo
Phase phase 3
Targets mTOR, FKBP-12
Sponsor Novartis Pharmaceuticals
Start date March 2012
End date August 2017
Trial size 303 participants
Trial identifier NCT01524783, 2011-002887-26, CRAD001T2302

Summary

The purpose of this study is to compare the antitumor activity of everolimus plus best supportive care versus placebo plus best supportive care in patients with advanced nonfunctional neuroendocrine tumor of gastrointestinal or lung origin.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Participants will receive everolimus 10mg once daily until disease progression, intolerable toxicity, or consent withdrawal
everolimus RAD001
After randomization, patients will receive everolimus once daily until disease progression, intolerable toxicity, or consent withdrawal
(Placebo Comparator)
Matching placebo to everolimus with same dose
everolimus placebo RAD001
After randomization, patients will receive everolimus placebo once daily until disease progression, intolerable toxicity, or consent withdrawal

Primary Outcomes

Measure
Progression free survival (PFS)
time frame: From date of randomization to progression or death

Secondary Outcomes

Measure
Overall survival (OS)
time frame: Every visit from randomization up to 5 years
Overall safety evaluation of everolimus versus placebo
time frame: Every visit from randomization up to 5 years
FACT-G total score over the duration of the study
time frame: Every Visit from randomization up to 5 years
Objective response rate (ORR)
time frame: Every Visit from randomization up to 5 years
Disease control rate (DCR)
time frame: 5 years
Change in Chromogranin A (CgA) and Neuron specific enolase (NSE) levels during the study
time frame: Every visit from baseline up to 5 years
Time to definitive deterioration in WHO Performance Status change during the study
time frame: Every visit up from randomization to 5 years
Pharmacokinetics (PK)
time frame: Visit 3 (Cycle 2, Study Day 29)
Time to definitive deterioration inWHO Performance Status change during the study
time frame: Every visit up from randomization to 5 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Pathologically confirmed, well differentiated (G1 or G2), advanced (unresectable or metastatic), neuroendocrine tumor of GI or lung origin - No history of and no active symptoms related to carcinoid syndrome - In addition to treatment-naive patients, patients previously treated with SSA, Interferon (IFN), one prior line of chemotherapy, and/or PRRT are allowed into the study. Pretreated patients must have progressed on or after the last treatment - Radiological documented disease progression within 6 months prior to randomization - Measurable disease - WHO performance status ≤1 - Adequate bone marrow, liver and renal function Exclusion Criteria: 1. Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, pancreatic islet cell carcinoma, insulinoma, glucagonoma, gastrinoma, goblet cell carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma 2. Patients with pancreatic NET or NET of origins other than GI or Lung 3. Patients with history of or active symptoms of carcinoid syndrome (e.g. flushing, diarrhea) 4. Patients with more than one line of prior chemotherapy 5. Prior targeted therapy 6. Hepatic locoregional therapy within the last 6 months 7. Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, deforolimus) 8. Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus) 9. Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus 10. Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy 11. Patients who have any severe and/or uncontrolled medical conditions such as: - unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to randomization, serious uncontrolled cardiac arrhythmia - active or uncontrolled severe infection - liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable HBV-DNA and/or positive HbsAg, quantifiable HCV-RNA) 12. Chronic treatment with corticosteroids or other immunosuppressive agents 13. Known history of HIV seropositivity 14. Pregnant or nursing (lactating) women Other protocol-defined inclusion/exclusion criteria may apply.

Additional Information

Official title A Randomized, Double-blind, Multicenter, Phase III Study of Everolimus (RAD001) Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in the Treatment of Patients With Advanced NET of GI or Lung Origin
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Novartis.