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:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00510068
First received: July 31, 2007
Last updated: May 27, 2014
Last verified: May 2014
  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:

  1. Patients must have advanced (unresectable or metastatic) biopsy-proven pancreatic NET
  2. Measurable disease by radiologic assessment
  3. Adequate blood work
  4. Performance Status 0-2 : Ability to be out of bed most of the time
  5. Adult male or female patients ≥ 18 years of age
  6. Women of childbearing potential must have a negative serum pregnancy test
  7. Written informed consent from patients must be obtained in accordance to local guidelines

Exclusion criteria:

  1. 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
  2. Other chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to starting this trial
  3. 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
  4. Prior therapy with the same kind of medication (mTOR inhibitors: sirolimus, temsirolimus, everolimus).
  5. Uncontrolled diabetes mellitus Patients who have any severe and/or uncontrolled medical conditions such as:
  6. Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent
  7. Patients with a known history of HIV seropositivity
  8. No other prior or concurrent cancer at the time enrolling to this trial

Other protocol defined inclusion/ exclusion criteria applied

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00510068

  Show 83 Study Locations
Sponsors 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, 2006-006819-75
Study First Received: July 31, 2007
Results First Received: November 11, 2011
Last Updated: May 27, 2014
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:
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on September 29, 2014