Phase 3
N=410
Efficacy and Safety of Everolimus (RAD001) Compared to Placebo in Patients With Advanced Neuroendocrine Tumors
Advanced Neuroendocrine Tumors of Pancreatic Origin
Bottom Line
View on ClinicalTrials.gov: NCT00510068 ↗Enrolled (actual)
410
Serious AEs
38.6%
Results posted
Dec 2011
Primary outcome: Primary: Time to Progression Free Survival (PFS) Based as Per Investigator Using Kaplan-Meier Methodology — 11.04; 4.60 Months
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Everolimus (Drug); Everolimus Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Feb 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to Progression Free Survival (PFS) Based as Per Investigator Using Kaplan-Meier Methodology |
11.04; 4.60 | — |
| SECONDARY Percentage of Participants With Objective Response Rate ( CR {Complete Response} OR PR {Partial Response}) |
4.8; 2.0 | — |
| SECONDARY Overall Survival |
44.02; 37.68 | — |
| SECONDARY Progression Free Survival According to Ki-67 Levels Categorized as: Less Than or Equal to 2%, > 2% to Less Than or Equal to 5% and > 5% |
12.52; 3.68; 10.94; 8.48; 7.69; 3.15 | — |
| SECONDARY Progression Free Survival According to Chromogramin A Tumor Marker (CgA) Baseline Level and According to CgA Early Response |
11.17; 4.90; 8.54; 4.34; 8.54; 5.70 | — |
| SECONDARY Progression Free Survival According to Neuron Specific Enolase Tumor Marker (NSE) Baseline Level and According to NSE Early Response |
13.86; 5.36; 8.11; 2.83; 8.11; 3.06 | — |
| SECONDARY Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) |
203; 198; 111; 23; 84; 52 | — |
| SECONDARY Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) (Open-label Period) |
221; 122; 108 | — |
| SECONDARY Evaluation of Pharmacokinetics (PK) Parameter: AUC0-t Last |
594; 481 | — |
| SECONDARY Evaluation of Pharmacokinetics (PK) Parameters: Cmax, Cmin |
62.4; 27.4; 9.80; 12.2 | — |
| SECONDARY Evaluation of Pharmacokinetics (PK) Parameter: CL/F |
20.2; 10.7 | — |
| SECONDARY Evaluation of Pharmacokinetics (PK) Parameter: Tmax -Time to Maximum (Peak) Drug Concentration |
1.17; 3.0 | — |
| SECONDARY Analysis of Time to Definitive Deterioration of WHO Performance Status Using Kaplan-Meier |
94.4; 91.8; 90.6; 86.3 | — |
| SECONDARY Plasma Angiogenesis Marker: Basic Fibroblast Growth Factor (bFGF) |
52.59; 51.49; 38.43; 58.33; 51.97; 59.08 | — |
| SECONDARY Plasma Angiogenesis Marker: Placental Growth Factor (PLGF) |
45.82; 32.92; 25.78; 35.38; 26.55; 33.84 | — |
| SECONDARY Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 1 (sVEGFR1) |
264.18; 256.69; 307.46; 299.03; 263.81; 253.37 | — |
| SECONDARY Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 2 (sVEGFR2) |
30061.30; 31299.61; 22691.18; 30223.21; 22021.23; 29264.67 | — |
| SECONDARY Plasma Angiogenesis Marker: Vascular Endothelial Growth Factor (VEGF) |
265.09; 326.16; 243.03; 326.78; 280.18; 292.27 | — |
Summary
The purpose of this study was to evaluate progression free survival in those participants assigned everolimus 10 mg/day plus Best Supportive Care versus those assigned to placebo plus Best Supportive Care in Advanced Neuroendocrine Tumors of pancreatic origin.
Eligibility Criteria
Inclusion criteria
- Patients must have advanced (unresectable or metastatic) biopsy-proven pancreatic NET
- Measurable disease by radiologic assessment
- Adequate blood work
- Performance Status 0-2 : Ability to be out of bed most of the time
- Adult male or female patients ≥ 18 years of age
- Women of childbearing potential must have a negative serum pregnancy test
- Written informed consent from patients must be obtained in accordance to local guidelines
Exclusion criteria
- Patients with severe kind of (poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma) cancer are not eligible
- Other chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to starting this trial
- Hepatic artery procedure called embolization within the last 6 months (1 month if there are other sites of measurable disease), or cryoablation/ radiofrequency ablation of hepatic metastasis within 2 months of enrollment
- Prior therapy with the same kind of medication (mTOR inhibitors: sirolimus, temsirolimus, everolimus).
- Uncontrolled diabetes mellitus Patients who have any severe and/or uncontrolled medical conditions such as:
- Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent
- Patients with a known history of HIV seropositivity
- No other prior or concurrent cancer at the time enrolling to this trial
Other protocol defined inclusion/ exclusion criteria applied
Data sourced from ClinicalTrials.gov (NCT00510068). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.