This is a phase II study to evaluate RAD001 (Everolimus) in terms of 4-month progression-free survival rate (primary end-point) and response rate, toxicity, overall survival and biomarker assessment (secondary end-points) in patients with metastatic or recurrent gastric cancer with pS6 Ser 240/4 expression. Eligibility criteria include pathologically proven non-resectable adenocarcinoma of stomach with measurable disease who failed previous first-line palliative chemotherapy including fluoropyrimidine and platinum with high expression of pS6 Ser 240/4. Oral RAD001 (everolimus) 10mg daily will be administered and the dose will be adjusted according to the observed clinical toxicities. Treatment will be continued until disease progression or patient's intolerability to the study drug. A study requires 40 assessable subjects to decide whether the proportion of patients who are free from progression at 4 months (16 weeks), P, is less than or equal to 0.1 or greater than or equal to 0.25 with a target error rate of 0.05 and β of 0.2. If the number of responses is 7 or less, the hypothesis that P \>= 0.250 is rejected with a target error rate of 0.200 and an actual error rate of 0.182. If the investigators assume that drop-out rate is 10%, total accrual patient will be 45.
Methodology: Prospective, non blinded, open label, single center phase II study Criteria for evaluation: Assessment of response will be assessed radiologically according to RECIST criteria after completion of the two cycles. Evaluation will be by physical examination, chest X-ray, abdomen-pelvis CT scan Safety criteria: Physical examination, vital signs, performance status, CBC, serum chemistry, NCI CTC V.3.0
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
45
RAD001 (everolimus) 10 mg daily, orally without interruption. 1 cycle is equal to 4-week treatment. Treatment will be continued unless disease progression or intolerability.
Asan Medical Center
Songpa-gu, Seoul, South Korea
4-month progression-free survival
Progression-free survival is defined as the time from the first treatment to the onset of progressive disease per RECIST criteria or to the date of death whichever comes first. For patients who do not experience progressive disease or death, the progression-free survival duration will be right censored on the last disease assessment date.
Time frame: up to 3years
Response rate
evaluated with abdominal and pelvic dynamic CT scan every 8 weeks, using RECIST version 1.0
Time frame: Up to 1year
Number of participants with adverse events
Adverse events will be graded according to Common Terminology Criteria for Adverse events version 4.0
Time frame: Monitoring of adverse events will be contineud for at least 28days following the last dose of study treatment
Overall survival
Overall survival duration is calculated as time from the first treatment to the date of death. For patients who are still alive at the cut-off date for statistical reporting, the overall survival duration will be right censored on the last known alive date.
Time frame: Up to 3years
Biomarker assessment
Tumor tissues obtained by tumor tissues can be used for immunohistochemistry(IHC) of pS6 Ser 240/4. In patients who did not receive gastrectomy tumor biopsies will be obtained at screening(before everolimus treatment) and after two cycles of treatment. Scoring of all IHC results is based on the percentage of positive cells. The percentage of positive cells is scored as: 0 (0%); 1 (≤10%); 2 (11-33%); 3 (34-66%); 4 (≥67%).
Time frame: 24months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.