Everolimus Plus Best Supportive Care vs Placebo Plus Best Supportive Care in the Treatment of Patients With Advanced Neuroendocrine Tumors (GI or Lung Origin) (RADIANT-4)
|ClinicalTrials.gov Identifier: NCT01524783|
Recruitment Status : Active, not recruiting
First Posted : February 2, 2012
Results First Posted : December 28, 2016
Last Update Posted : December 8, 2017
|Condition or disease||Intervention/treatment||Phase|
|Advanced NET of GI Origin Advanced NET of Lung Origin Neuroendocrine Tumors||Drug: Everolimus Drug: Everolimus Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||302 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
|Actual Study Start Date :||March 30, 2012|
|Primary Completion Date :||November 28, 2014|
|Estimated Study Completion Date :||December 28, 2020|
Experimental: Everolimus + BSC
Participants received everolimus 10mg once daily until disease progression, intolerable toxicity, or consent withdrawal plus best supportive care (BSC)
After randomization, patients will receive everolimus once daily until disease progression, intolerable toxicity, or consent withdrawal
Other Name: RAD001
Placebo Comparator: Everolimus Placebo + BSC
Participants received matching placebo to everolimus with same dose, plus best supportive care (BSC)
Drug: Everolimus Placebo
After randomization, patients will receive everolimus placebo once daily until disease progression, intolerable toxicity, or consent withdrawal
- Progression Free Survival (PFS) Based on Central Radiology Assessment Per Kaplan-Meier [ Time Frame: From date of randomization to progression or death up to 18 months ]PFS is defined as the time from randomization to the date of the first documented tumor progression as per modified RECIST 1.0 or death from any cause, whichever comes first. Progression is assessed by cat scan (CT) and/or magnetic resonance imaging (MRI).
- Overall Survival (OS) Using Kaplan-Meier [ Time Frame: Every visit from randomization up to 18 months ]OS is defined as the time from the date of randomization to date of death due to any cause.
- Overall Safety Evaluation of Everolimus Versus Placebo [ Time Frame: Every visit from randomization up to 5 years ]The assessment of safety will be based mainly on the frequency and type of treatment emergent adverse events and on the number of laboratory values that fall outside of pre-determined ranges. Other safety data (e.g. vital signs) will be considered as appropriate. Safety events will be graded using the CTCAE V4.03 (Common Terminology Criteria for Adverse Events).
- FACT-G Total Score Over the Duration of the Study [ Time Frame: Every Visit from randomization up to 5 years ]FACT-G is a self-assessed health-related quality of life questionnaire. The questionnaire is comprised of 27 questions, scored 0 to 4, examining physical, social/family, emotional, and functional well-being. Deterioration is defined as a decrease by at least 7 points compared to baseline.
- Objective Response Rate (ORR) [ Time Frame: Every Visit from randomization up to 5 years ]ORR will be assessed per modified RECIST 1.0. ORR is the proportion of patients with a best overall response of complete response (CR) or partial response (PR).
- Disease Control Rate (DCR) [ Time Frame: 5 years ]The estimated average treatment duration is at least 5-8.5 months until disease progression. DCR will be assessed per modified RECIST 1.0. DCR is the proportion of patients with best overall response of CR, PR or stable disease (SD).
- Change in Chromogranin A (CgA) and Neuron Specific Enolase (NSE) Levels During the Study [ Time Frame: Every visit from baseline up to 5 years ]The estimated average treatment duration is at least 5-8.5 months until disease progression. CgA and NSE are potential biomarkers for tumor response. Change from baseline will be noted and correlated with tumor response.
- Time to Definitive Deterioration in WHO Performance Status Change During the Study [ Time Frame: Every visit up from randomization to 5 years ]The estimated average duration is at least 5-8.5 months until disease progression. WHO Performance Status is a scale rated from 0 (normal) to 5 (dead) by a healthcare professional to assess the overall status of a patient. Deterioration is defined as an increase of at least one category compared to baseline.
- Pharmacokinetics (PK) [ Time Frame: Visit 3 (Cycle 2, Study Day 29) ]A single blood sample to determine the exposure of everolimus at the steady-state pre-dose concentration (Cmin).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01524783
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|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|