Efficacy and Safety of Everolimus (RAD001) Compared to Placebo in Patients With Advanced Neuroendocrine Tumors (RADIANT-3)
This study is ongoing, but not recruiting participants.
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00510068
First received: July 31, 2007
Last updated: April 16, 2013
Last verified: April 2013
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Purpose
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
| Condition | Intervention | Phase |
|---|---|---|
|
Advanced Neuroendocrine Tumors |
Drug: Everolimus Drug: Placebo to Everolimus |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Randomized Double-blind Phase III Study of RAD001 10 mg/d Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in the Treatment of Patients With Advanced Pancreatic Neuroendocrine Tumor (NET) |
Resource links provided by NLM:
Further study details as provided by Novartis:
Primary Outcome Measures:
- Time to Progression Free Survival (PFS) Based as Per Investigator Using Kaplan-Meier Methodology [ Time Frame: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010 ] [ Designated as safety issue: No ]Progression of disease is defined as the time from study start to the date of first documented progression of disease or death due to any cause. Progression of disease is defined by RECIST criteria: Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions.
Secondary Outcome Measures:
- Percentage of Participants With Objective Response Rate ( CR {Complete Response} OR PR {Partial Response}) [ Time Frame: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010 ] [ Designated as safety issue: No ]Objective Response defined by RECIST criteria: Partial response (PR) must have ≥ 30% decrease in the sum of the longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks . Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) [ Time Frame: on or after the start of double-blind study medication until no later than 28 days after double-blind study medication discontinuation ] [ Designated as safety issue: Yes ]Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
- Time to Overall Survival [ Time Frame: Baseline, to death- no time limit ] [ Designated as safety issue: Yes ]Overall Survival Rate is the time from study start to death from any cause.
- Evaluation of Pharmacokinetics (PK) Parameters [ Time Frame: Day 1 of every cycle (28 days/cycle) throughout the study ] [ Designated as safety issue: No ]The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. The PK parameters were: area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-t last), area under the concentration time curve from time zero to time t, where t is the end of the dosing interval (AUC0-t), maximum (peak) drug concentration (Cmax), time to maximum (peak) drug concentration (tmax), and minimum (trough) drug concentration (Cmin).
- Changes From Baseline in Serum Biochemical Tumor Markers, Such as Chromogranin A (CgA) and Neuron Specific Enolase (NSE) [ Time Frame: If elevated at baseline, evaluated every cycle visit (28 days/cycle) ] [ Designated as safety issue: No ]Baseline levels of serum CgA and NSE were characterized relative to the upper limited of normal (ULN). CgA levels exceeding 2 x ULN were considered to be 'Elevated'; otherwise considered as "Non-elevated". NSE levels exceeding 2 x ULN were considered to be 'Elevated'; otherwise considered as "Non-elevated".
| Enrollment: | 410 |
| Study Start Date: | July 2007 |
| Estimated Study Completion Date: | December 2017 |
| Primary Completion Date: | February 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Everolimus 10 mg/day
Participants received 10 mg per day of Everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Drug: Everolimus
A 10-mg dose of everolimus was given by continuous oral daily dosing of two 5-mg tablets.
Other Name: RAD001
|
|
Placebo Comparator: Placebo
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
Drug: Placebo to Everolimus
a 10-mg dose of matching placebo to Everolimus was given by continuous oral daily dosing of two 5-mg tablets.
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00510068
Show 22 Study Locations
Show 22 Study LocationsSponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
More Information
Additional Information:
No publications provided by Novartis
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Novartis ( Novartis Pharmaceuticals ) |
| ClinicalTrials.gov Identifier: | NCT00510068 History of Changes |
| Other Study ID Numbers: | CRAD001C2324, EudraCT 2006-006819-75 |
| Study First Received: | July 31, 2007 |
| Results First Received: | November 11, 2011 |
| Last Updated: | April 16, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Novartis:
|
Phase III Advanced Neuroendocrine Tumor in adults RAD001 NET |
everolimus mTOr islet cell neuroendocrine |
Additional relevant MeSH terms:
|
Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Nerve Tissue Everolimus Sirolimus Immunosuppressive Agents |
Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Antifungal Agents Anti-Infective Agents Anti-Bacterial Agents |
ClinicalTrials.gov processed this record on May 23, 2013