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)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01524783
First received: December 22, 2011
Last updated: January 30, 2014
Last verified: January 2014

December 22, 2011
January 30, 2014
March 2012
February 2018   (final data collection date for primary outcome measure)
Progression free survival (PFS) [ Time Frame: From date of randomization to progression or death ] [ Designated as safety issue: No ]
The estimated average duration from randomization date is at least 5-8.5 months until disease progression. 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 CT and/or MRI.
Time to Progression free survival (PFS) [ Time Frame: From date of randomization to the date of death ] [ Designated as safety issue: No ]
The estimated average duration from randomization date is at least 5-8.5 months until disease progression. 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 CT and/or MRI.
Complete list of historical versions of study NCT01524783 on ClinicalTrials.gov Archive Site
  • Overall survival (OS) [ Time Frame: Every visit from randomization up to 5 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    The estimated average survival duration is at least 30 to 46 months from randomization date.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) which defines the severity of adverse events from Grade 0 (None) to Grade 4 (life-threatening consequences) and Grade 5 (Death due to AE).
  • FACT-G total score over the duration of the study [ Time Frame: Every Visit from randomization up to 5 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    A single blood sample to determine the exposure of everolimus at the steady-state pre-dose concentration (Cmin).
  • Time to definitive deterioration inWHO Performance Status change during the study [ Time Frame: Every visit up from randomization to 5 years ] [ Designated as safety issue: No ]
    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.
  • Time to Overall survival (OS) [ Time Frame: From date of randomization to the date of death ] [ Designated as safety issue: No ]
    The estimated average survival duration is at least 30 to 46 months from randomization date. 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: Each visit from randomization up to 5 years ] [ Designated as safety issue: Yes ]
    The estimated average survival duration is at least 30 to 46 months from randomization date.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) which defines the severity of adverse events from Grade 0 (None) to Grade 4 (life-threatening consequences) and Grade 5 (Death due to AE).
  • Time to definitive deterioration in FACT-G total score over the duration of the study [ Time Frame: Every 2 - 3 months up to 5 years ] [ Designated as safety issue: No ]
    The estimated average duration is at least 5-8.5 months until disease progression. 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.
  • Time to Objective response rate (ORR) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    The estimated average duration is at least 5-8.5 months until disease progression. 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 inWHO Performance Status change during the study [ Time Frame: Every visit up from randomization to 5 years ] [ Designated as safety issue: No ]
    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.
Not Provided
Not Provided
 
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

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 advanced nonfunctional neuroendocrine tumor of gastrointestinal or lung origin.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Advanced NET of GI Origin
  • Advanced NET of Lung Origin
  • Neuroendocrine Tumors
  • Drug: Everolimus
    After randomization, patients will receive everolimus once daily until disease progression, intolerable toxicity, or consent withdrawal
    Other Name: RAD001
  • Drug: Everolimus Placebo
    After randomization, patients will receive everolimus placebo once daily until disease progression, intolerable toxicity, or consent withdrawal
    Other Name: RAD001
  • Experimental: Everolimus
    Participants will receive everolimus 10mg once daily until disease progression, intolerable toxicity, or consent withdrawal
    Intervention: Drug: Everolimus
  • Placebo Comparator: Everolimus Placebo
    Matching placebo to everolimus with same dose
    Intervention: Drug: Everolimus Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
302
February 2018
February 2018   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Pathologically confirmed, well differentiated (G1 or G2), advanced (unresectable or metastatic), neuroendocrine tumor of GI or lung origin
  • No history of and no active symptoms related to carcinoid syndrome
  • In addition to treatment-naive patients, patients previously treated with SSA, Interferon (IFN), one prior line of chemotherapy, and/or PRRT are allowed into the study. Pretreated patients must have progressed on or after the last treatment
  • Radiological documented disease progression within 6 months prior to randomization
  • Measurable disease
  • WHO performance status ≤1
  • Adequate bone marrow, liver and renal function

Exclusion Criteria:

  1. Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, pancreatic islet cell carcinoma, insulinoma, glucagonoma, gastrinoma, goblet cell carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma
  2. Patients with pancreatic NET or NET of origins other than GI or Lung
  3. Patients with history of or active symptoms of carcinoid syndrome (e.g. flushing, diarrhea)
  4. Patients with more than one line of prior chemotherapy
  5. Prior targeted therapy
  6. Hepatic locoregional therapy within the last 6 months
  7. Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, deforolimus)
  8. Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
  9. Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
  10. Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy
  11. Patients who have any severe and/or uncontrolled medical conditions such as:

    • unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to randomization, serious uncontrolled cardiac arrhythmia
    • active or uncontrolled severe infection
    • liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable HBV-DNA and/or positive HbsAg, quantifiable HCV-RNA)
  12. Chronic treatment with corticosteroids or other immunosuppressive agents
  13. Known history of HIV seropositivity
  14. Pregnant or nursing (lactating) women

Other protocol-defined inclusion/exclusion criteria may apply.

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Austria,   Belgium,   Canada,   China,   Colombia,   Czech Republic,   Germany,   Greece,   Hungary,   Italy,   Japan,   Korea, Republic of,   Lebanon,   Netherlands,   Poland,   Russian Federation,   Saudi Arabia,   Slovakia,   South Africa,   Spain,   Taiwan,   Thailand,   Turkey,   United Kingdom
 
NCT01524783
CRAD001T2302, 2011-002887-26
Yes
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP