A study of everolimus plus best supportive care versus placebo plus best supportive care in the treatment of patients with advanced neuroendocrine cancer of gastrointestinal or lung origin.

• Register: EUCTR
• Last refreshed on: 15 September 2020
• Main ID: EUCTR2011-002887-26-CZ
• Date of registration: 14/02/2012
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A study of everolimus plus best supportive care versus placebo plus best supportive care in the treatment of patients with advanced neuroendocrine cancer of gastrointestinal or lung origin.
• Scientific 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. - RADIANT-4
• Date of first enrolment: 28/05/2012
• Target sample size: 285
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002887-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Canada, China, Colombia, Czech Republic, Egypt, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Lebanon, Netherlands, Norway, Peru, Poland, Russian Federation, Saudi Arabia, Slovakia, South Africa, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Informacní služba - klin. hodnocení
• Affiliation: Novartis s.r.o.

• Name: Informacní služba - klin. hodnocení
• Affiliation: Novartis s.r.o.

Key inclusion & exclusion criteria

Inclusion criteria:
1.Pathologically confirmed, well differentiated (G1 or G2), advanced (unresectable or metastatic), neuroendocrine tumor of GI or lung origin.
2.No history of and no active symptoms related to carcinoid syndrome (or other hypersecretory syndromes).
3.Patients treated with prior SSA and/or Interferon (IFN) may be included. These patients must discontinue treatment prior to the day of randomization as follows:
4.Radiological documented disease progression within 6 months prior to randomization
5.Measurable disease
6.WHO performance status =1
7.Adequate bone marrow, lifer and renal function
Other protocol-defined inclusion/exclusion criteria may apply
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 190
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 95

Exclusion criteria:
1.Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, pancreatic islet cell carcinoma, gastrinoma, goblet cell carcinoid, 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.Prior systemic cytotoxic chemotherapy or targeted therapy.
6.Hepatic intra-arterial embolization within the last 6 months (or 1 month if there is measurable disease in other organs besides the liver)
7.Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, deforolimus).
8.Known intolerance or hypersensitivity to everolimus or other rapamycins (e.g. sirolimus, temsirolimus).
9.Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus.
10.Uncontrolled diabetes mellitus.
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, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory tests.
Other protocol-defined exclusion criteria may apply



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Advanced neuroendocrine tumor (NET) of GI or lung origin
MedDRA version: 14.1 Level: PT Classification code 10052399 Term: Neuroendocrine tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Trade Name: Afinitor®
Product Name: Everolimus
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: Everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Tumor assesments as per modified RECIST 1.0 based on local assessment. Progression free survival (PFS)

Main Objective: Determinate whether treatment with everolimus plus best supportive care prolongs PFS compared to placebo plus best supportive care in patients with advanced NET of GI or lung origin

Timepoint(s) of evaluation of this end point: Every 12 weeks until disease progression, start of futher anti-tumor therapy or intolerable toxicity, whichever comes first.

Secondary Objective: Safety evaluation and tolerability of everolimus

Secondary Outcome(s)

Secondary end point(s): 1. Overall Survival (OS).
2. Safety evaluation and efficacy in everolimus.
3. FACT-G total score over time.
4. Objective response rate (ORR).
5. Changes from baseline in Chromogranin A (CgA) and Neuron specific enolase (NSE) levels.
6. Pre-dose concentration (Cmin)

Timepoint(s) of evaluation of this end point: 1. Continuously during the treatment period. Every 12 weeks during follow-up.
2. Continuously
3. Every 12 weeks until start of futher anti-tumor therapy.
4. Every 12 weeks until disease progression, start of futher anti-tumor. therapy or intolerable toxicity, whichever comes first.
5. Every visit until end of treatment.
6. Cycle 2 (Day 29)

Secondary ID(s)

2011-002887-26-BE

CRAD001T2302

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 17/05/2012
Contact: