Everolimus Plus Best Supportive Care vs Placebo Plus Best Supportive Care in the Treatment of Patients With Advanced Neuroendocrine Tumors (GI or Lung Origin) - Full Text View

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 Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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:

MedlinePlus related topics: Cancer

Drug Information available for: Sirolimus Everolimus Temsirolimus

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

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.

Secondary Outcome Measures:

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.

Estimated Enrollment:	285
Study Start Date:	March 2012
Estimated Study Completion Date:	January 2018
Estimated Primary Completion Date:	November 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Everolimus Participants will receive everolimus 10mg once daily until disease progression, intolerable toxicity, or consent withdrawal	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 Matching placebo to everolimus with same dose	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
Genders Eligible for Study:	Both
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

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

Contacts

Contact: Novartis Pharmaceuticals	1-888-669-6682
Contact: Novartis Pharmaceuticals

Show 151 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01524783 History of Changes
Other Study ID Numbers:	CRAD001T2302, 2011-002887-26
Study First Received:	December 22, 2011
Last Updated:	April 1, 2013
Health Authority:	United States: Food and Drug Administration

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
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 19, 2013

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)