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Trial record 1 of 1 for:    RADIANT4
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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: November 1, 2016
Last verified: November 2016
  Purpose
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.

Condition Intervention Phase
Advanced NET of GI Origin
Advanced NET of Lung Origin
Neuroendocrine Tumors
Drug: Everolimus
Drug: Everolimus Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Progression Free Survival (PFS) Based on Central Radiology Assessment Per Kaplan-Meier [ Time Frame: From date of randomization to progression or death up to 18 months ]
    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 cat scan (CT) and/or magnetic resonance imaging (MRI).


Secondary Outcome Measures:
  • Overall Survival (OS) Using Kaplan-Meier [ Time Frame: Every visit from randomization up to 18 months ]
    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 ]
    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).

  • FACT-G Total Score Over the Duration of the Study [ Time Frame: Every Visit from randomization up to 5 years ]
    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 ]
    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 ]
    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 ]
    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 ]
    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) ]
    A single blood sample to determine the exposure of everolimus at the steady-state pre-dose concentration (Cmin).


Enrollment: 302
Study Start Date: March 2012
Estimated Study Completion Date: December 2020
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus + BSC
Participants received everolimus 10mg once daily until disease progression, intolerable toxicity, or consent withdrawal plus best supportive care (BSC)
Drug: Everolimus
After randomization, patients will receive everolimus once daily until disease progression, intolerable toxicity, or consent withdrawal
Other Name: RAD001
Placebo Comparator: Everolimus Placebo + BSC
Participants received matching placebo to everolimus with same dose, plus best supportive care (BSC)
Drug: Everolimus Placebo
After randomization, patients will receive everolimus placebo once daily until disease progression, intolerable toxicity, or consent withdrawal

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

  • 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
  • Patients with pancreatic NET or NET of origins other than GI or Lung
  • Patients with history of or active symptoms of carcinoid syndrome (e.g. flushing, diarrhea)
  • Patients with more than one line of prior chemotherapy
  • Prior targeted therapy
  • Hepatic locoregional therapy within the last 6 months
  • Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, deforolimus)
  • Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
  • Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
  • Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy
  • 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)
  • Chronic treatment with corticosteroids or other immunosuppressive agents
  • Known history of HIV seropositivity
  • Pregnant or nursing (lactating) women

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01524783

  Show 105 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01524783     History of Changes
Other Study ID Numbers: CRAD001T2302
2011-002887-26 ( Registry Identifier: EudraCT )
Study First Received: December 22, 2011
Results First Received: March 26, 2016
Last Updated: November 1, 2016

Keywords provided by Novartis:
Neuroendocrine tumor
NET
progressive
advanced
gastrointestinal
GI or lung origin
nonfunctional
everolimus
Advanced NET of GI origin
Advanced NET of lung origin

Additional relevant MeSH terms:
Neuroendocrine Tumors
Carcinoid Tumor
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Everolimus
Sirolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on April 24, 2017