A randomized, double-blind, multi-center phase III study comparing everolimus (RAD001) plus best supportive care versus placebo plus best supportive care in patients with advanced gastric cancer after progression on prior systemic chemotherapy
- Conditions
- advanced gastric cancerMedDRA version: 9.1Level: PTClassification code 10017758Term: Gastric cancer
- Registration Number
- EUCTR2008-006544-20-BE
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 633
• Male or female patients = 18 years old
• Histologically or cytologically confirmed and documented gastric adenocarcinoma. Patients with advanced
gastro-esophageal junction adenocarcinoma, of which the majority, as assessed by the investigator, involves the
stomach, will be eligible for inclusion in the study.
• Documented progression after 1 or 2 prior systemic chemotherapy lines for advanced disease
Note: One line of therapy in the advanced disease setting consists of one or more drugs which are given for 21
days or longer
Note: Prior adjuvant/neoadjuvant therapy is allowed. If recurrence occurred during adjuvant/neoadjuvant
therapy or = 24 weeks after adjuvant/neoadjuvant therapy completion, the adjuvant/neoadjuvant therapy will be
considered as one prior line of systemic chemotherapy for advanced disease
Note: Prior treatment with chemotherapy combined with targeted agents is permitted
• ECOG performance status of = 2
• Patients with the following laboratory parameters can be included:
o Absolute neutrophil count = 1.5 x 109/L (= 1500/mm3)
o Platelets = 100 x 109/L (= 100,000/mm3)
o Hemoglobin (Hgb) = 8 g/dL (= 4.9 mmol/L)
o INR = 2.0
o Serum creatinine = 2 x Upper Limit of Normal (ULN)
o Adequate liver function as defined as:
• If there is no evidence of liver metastasis: ALT and AST = 2.5 x ULN
• If liver metastases are documented: ALT and AST = 5.0 x ULN
o Serum bilirubin = 1.5 x ULN
o Total serum calcium (corrected for serum albumin) or ionized calcium = Lower Limit of Normal (LLN)
o Serum potassium = LLN
Note: Calcium, potassium, magnesium and phosphate supplements may be given to correct values that are below
the LLN, but must be documented as corrected prior to patients enrolling on the study
• Women of childbearing potential must have a negative serum pregnancy test within 7 days of the first
administration of study treatments and must be willing to use adequate methods of contraception during the
study and for 8 weeks after last study drug administration
• Written informed consent
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
• Patients who have received > 2 prior lines of systemic therapy for advanced disease
See notes under inclusion criterion 3.
• Administration of anti-cancer therapy within 3 weeks prior to randomization, except for fluoropyrimidine
monotherapy, where randomization may occur 2 weeks after last dose.
• Known hypersensitivity to RAD001 (everolimus) or to its excipients, or to other rapamycins (e.g., sirolimus,
temsirolimus)
• Chronic treatment with steroids (except for oral, topical or local injection) or another immunosuppressive agent
• Major surgery = 2 weeks prior to randomization
Note: Patients must have recovered from the acute effects of surgery prior to randomization.
• Malignant ascites requiring invasive treatment (such as ascites drainage)
• Lack of resolution of all acute toxic effects of prior chemotherapy, prior radiotherapy, or surgical procedure
according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
Grade = 1, with the exception of neuropathy (inclusion of patients with neuropathy of Grade 2 or less is
permitted) and alopecia
• Patients with central nervous system metastases
• Known history of HIV seropositivity (HIV testing is not mandatory)
• Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin and acetylsalicylic
acid, as long as the INR is = 2.0)
• Any malignancy within 3 years prior to randomization, with the exception of adequately treated in-situ
carcinoma of the cervix uteri, basal or squamous cell carcinoma
• Any severe and/or uncontrolled medical conditions which could cause unacceptable safety risks or compromise
compliance with the protocol, such as:
o Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction = 24 weeks prior to
enrollment, serious uncontrolled cardiac arrhythmia
o Uncontrolled diabetes as defined by fasting serum glucose > 1.5 X ULN
o = Grade 3 hypercholesterolemia/hypertriglyceridemia or = Grade 2 hypercholesterolemia/hypertriglyceridemia
with history of coronary artery disease (despite lipid-lowering treatment if given)
o Acute and chronic, active infectious disorders and nonmalignant medical illnesses that are uncontrolled or
whose control may be jeopardized by the complications of this study therapy
o Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption
of study drugs, with the exception of prior gastrectomy (e.g., ulcerative disease, uncontrolled nausea, vomiting,
diarrhea, malabsorption syndrome).
Note: Data from the phase II Japanese study of RAD001 in AGC does not suggest that gastrectomy impairs the
absorption of RAD001.
o Active skin, mucosa, ocular or GI disorders of Grade > 1
o Chronic obstructive or chronic restrictive pulmonary disease including dyspnea at rest from any cause
• Patients who are enterally fed (e.g. via a nasogastric or nasojejunal tube, or via a gastrostomy or jejunostomy)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method