Neoplasms

All Conditions

Rare Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Analgesics

All Drugs and Chemicals

Antineoplastic Agents

Gastrointestinal Agents

Anti-Infective Agents

Everolimus

Loperamide

Antidiarrheals

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Participants received everolimus 10 mg once daily plus best supportive care (BSC) throughout the study

Participants received matching placebo once daily plus best supportive care (BSC) during the blinded period. Participants were allowed to crossover to treatment with everolimus 10mg once daily plus BSC during the open-label period.

Participants were treated with everolimus 10 mg (two 5 mg tablets) once daily orally taken

Participants were treated with two tablets of matching placebo once daily orally taken.

Placebo

Best supportive care includes all care provided to participants deemed necessary by the treating physician, such as but not restricted to anti-diarrheals and analgesics. The optimal care of the patient is based on the treating physician's best medical judgment.

Best suportive care (BSC)

Novartis Pharmaceuticals

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 progressive nonfunctional neuroendocrine tumor (NET) of gastrointestinal (GI) or lung origin without a history of, or current symptoms of carcinoid syndrome.

This was a prospective, multi-center, randomized, double-blind, parallel-group, placebo-controlled, two-arm Phase III study comparing the efficacy and safety of everolimus 10 mg daily to placebo in patients with advanced NET of GI or lung origin without a history of, or current symptoms of carcinoid syndrome.

After assessment of eligibility, participants qualifying for the study were randomized in a 2:1 ratio to receive either everolimus or matching placebo. Participants received daily oral doses of 10 mg everolimus or matching placebo as study drug. In both arms, the study drug was combined with best supportive care and treatment cycles were defined as 28 days. Participants were treated until disease progression as per Response Evaluation Criteria In Solid Tumors (RECIST) 1.0, intolerable toxicity, death, lost to follow-up or consent withdrawal. Regardless of the reason for study drug discontinuation, participants had a safety follow-up visit scheduled 30 days after the last dose of the study drug.

Per data monitoring committee recommendation, all participants on treatment with placebo were allowed to crossover to open-label treatment with everolimus. This change was implemented through protocol amendment 3 (issued on 06-May-2016) after which remaining participants entered into open-label phase of the study.

Everolimus Plus Best Supportive Care vs Placebo Plus Best Supportive Care in the Treatment of Patients With Advanced Neuroendocrine Tumors (GI or Lung Origin)

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

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

PFS is defined as the time from randomization to the date of the first documented tumor progression or death from any cause, whichever comes first.

Progression was defined using modified RECIST 1.0 and as per central radiology assessment as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. Progression was assessed by cat scan (CT) and/or magnetic resonance imaging (MRI).

For participants who had not progressed or died at the analysis cut-off date, PFS was censored at the date of the last adequate tumor evaluation date. An adequate tumour assessment is a tumour assessment with an overall response other than unknown.

The percentage event-free probability estimate is the estimated probability that a patient will remain event-free in PFS up to the specified time point.

OS is defined as the time from the date of randomization to date of death due to any cause. If a death had not been observed by the date of analysis cut-off, then OS was censored at the date of last contact. All participants randomized to placebo arm who crossed over to everolimus were censored.

ORR is defined as the proportion of patients with best overall response (BOR) of complete response (CR) or partial response (PR), according to central evaluation and as per modified RECIST 1.0.

CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.

DCR is defined as the proportion of subjects with best overall response of CR or PR or stable disease based on modified RECIST 1.0 and as per central radiology assessment.

CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.

Stable disease: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.

FACT-G is a self-assessed health-related quality of life questionnaire. The questionnaire is comprised of 27 questions examining physical, social/family, emotional, and functional well-being. Participants responded to the items on a five-point scale, ranging from 0: "Not at all" to 4: "Very much." The total score ranges from 0 to 108, with higher scores indicating a better patient-reported outcome/quality of life.

Definitive deterioration is defined as a decrease in the total score by at least 7 points compared to baseline with no further improvement.

Death was considered as worsening of the FACT-G total score if it occurred close to the last available assessment, where "close" was defined as twice the planned period between two assessments. Patients without definitive worsening prior to analysis cut-off or prior to start of another anticancer therapy were censored at the date of their last assessment.

CgA is a potential biomarker for tumor response. Blood samples were collected for assessment of CgA levels. Change from Baseline at a particular visit was calculated as the CgA level at that visit minus Baseline.

NSE is a potential biomarker for tumor response. Blood samples were collected for assessment of NSE levels. Change from Baseline at a particular visit was calculated as the NSE level at that visit minus Baseline.

WHO PS is a scale rated from 0 (fully active) to 5 (death) by a healthcare professional to assess the overall status of a patient: a lower score represents a higher ability to perform daily tasks. Deterioration is defined as an increase of at least one point compared to baseline. Deterioration is considered definitive if no improvements in the WHO PS status is observed at a subsequent time of measurement during the treatment period following the time point where the deterioration is observed. Death was considered as worsening of the WHO PS if it occurred close to the last available assessment, where "close" was defined as twice the planned period between two assessments. Patients without definitive worsening prior to analysis cut-off or prior to start of another anticancer therapy were censored at the date of their last assessment.

A pre-dose blood sample at day 29 was collected to determine the exposure of everolimus at the steady-state pre-dose concentration (Cmin). Cmin is provided for participants randomized to everolimus+BSC who received 10mg of everolimus daily and also for participants randomized to everolimus+BSC who received 5mg of everolimus daily which was required for a number of participants in the study experiencing adverse events requiring dose modifications

Any sign or symptom that occurs during the study treatment plus the 30 days post treatment. The safety set consists of all participants who received at least one dose of the study drug and had at least one post-baseline safety evaluation. Participants were analyzed according to treatment actually received: One participant randomized to everolimus arm received only placebo and therefore, appears in the placebo arm in the safety set

Participants received everolimus 10 mg once daily plus BSC throughout the study

Everolimus+BSC (Throughout Study)

Participants who crossed over from placebo arm (blinded period) to open-label treatment with everolimus 10mg once daily plus BSC

Everolimus +BSC (Crossover)

All participants who received everolimus 10 mg once daily plus BSC (including those who received everolimus+BSC from start to end of the study and those who received everolimus+BSC after crossover)

Everolimus+BSC (All)

Participants received matching placebo once daily plus best supportive care (BSC) during the blinded period.

Placebo+BSC (Blinded Period)

Participants received everolimus 10 mg once daily BSC throughout the study

Everolimus + BSC

Participants received matching placebo once daily plus BSC during the blinded period. Participants were allowed to crossover to treatment with everolimus 10mg once daily plus BSC during the open-label period

Placebo+BSC

Total

Age continuous at Baseline: Blinded Period

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Study Director

2 months

4 months

6 months

8 months

10 months

12 months

15 months

18 months

21 months

24 months

27 months

Placebo + BSC

The full analysis set (FAS) consists of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment arm and stratification factors they were assigned to at randomization.

Probability of Participants Remaining Event-Free in Progression-Free Survival (PFS) Based on Central Radiology Assessment

Overall Survival (OS)

Overall Response Rate (ORR) as Per Modified RECIST 1.0 According to Central Evaluation

Disease Control Rate (DCR) Based on Modified RECIST 1.0 and as Per Central Radiology Assessment

Time to Definitive Deterioration in Functional Assessment of Cancer Therapy - General (FACT-G) Questionnaire Total Score

Week 4

Week 8

Week 12

Week 16

Week 20

Week 24

Week 28

Week 32

Week 36

Week 40

Week 44

Week 48

Week 52

Week 56

Week 60

Week 64

Week 68

Week 72

Week 76

Week 80

Week 84

Week 88

Week 92

Week 96

Week 100

Week 104

Week 108

Week 112

Week 116

The full analysis set (FAS) consists of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment arm and stratification factors they were assigned to at randomization. Number analyzed signified number of participants with available data for this outcome measure at specified timepoints.

Change From Baseline in Chromogranin A (CgA) Levels

Change From Baseline in Neuron Specific Enolase (NSE) Levels

Time to Definitive Deterioration in World Health Organization (WHO) Performance Status (PS) Change

10mg daily dose

5mg daily dose

All patients who received at least one dose of the study drug with evaluable blood samples for this endpoint.

Pharmacokinetics (PK): Predose Concentration (Cmin) of Everolimus at Day 29

On-treatment deaths

Total deaths

Deaths on-treatment were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of approximately 8 years.

Total Deaths were collected from first dose of study treatment until end of post-treatment survival follow, up to maximum duration of approximately 8 years.

Everolimus + BSC (Throughout the Study)

Participants received matching placebo once daily plus BSC during the blinded period

Placebo + BSC (Blinded Period)

The safety set consists of all participants who received at least one dose of the study drug and had at least one post-baseline safety evaluation. Participants were analyzed according to treatment actually received: One participant randomized to everolimus arm received only placebo and therefore, appears in the placebo arm in the safety set

Spots Global Cancer Trial Database for gi or lung origin