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 cancer; MedDRA version: 9.1Level: PTClassification code 10017758Term: Gastric cancer

• Registration Number: EUCTR2008-006544-20-FR
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-07-02
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 633

Inclusion Criteria

• Male or female patients = 18 years old
• Histologically or cytologically confirmed and documented gastric adenocarcinoma. Patients with advanced gastro-esophageal junction adenocarcinoma, of which at least 50% involves the stomach, will be eligible for inclusion in the study.
• Documented progression after 1 or 2 prior systemic chemotherapy treatments for advanced disease
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 regimen of systemic chemotherapy for advanced disease
• 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 = 1.5mg/dL (= 26 µmol/L)
o Amylase and lipase £ 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 3 months 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

Exclusion Criteria

• Patients who have received > 2 prior systemic therapies for advanced disease
Note: 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 regimen of systemic chemotherapy for advanced disease
• 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 (excluding alopecia) of prior chemotherapy, prior radiotherapy, or surgical procedure according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade = 1
• 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 severe and/or uncontrolled medical conditions 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 who have 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 show that gastrectomy impairs the absorption of RAD001.
o Active skin, mucosa, ocular or GI disorders of Grade > 1
o Significant deterioration of lung function, defined as any of the following: 30% decrease in predicted lung volumes, and/or 30% decrease in DLCO, and/or = 88% O2 saturation at rest on room air.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified