RAD001 in Advanced Gastric Cancer Who Failed Standard First-line Treatment With pS6 Ser 240/4 Expression
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.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of RAD001 (Everolimus) for 2nd Line Treatment After Failure of Fluoropyrimidine Plus Platinum Chemotherapy in Patients With Metastatic or Recurrent Gastric Cancer With pS6 Ser 240/4 Expression|
- 4-month progression-free survival [ Time Frame: up to 3years ] [ Designated as safety issue: No ]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.
- Response rate [ Time Frame: Up to 1year ] [ Designated as safety issue: No ]evaluated with abdominal and pelvic dynamic CT scan every 8 weeks, using RECIST version 1.0
- Number of participants with adverse events [ Time Frame: Monitoring of adverse events will be contineud for at least 28days following the last dose of study treatment ] [ Designated as safety issue: Yes ]Adverse events will be graded according to Common Terminology Criteria for Adverse events version 4.0
- Overall survival [ Time Frame: Up to 3years ] [ Designated as safety issue: No ]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.
- Biomarker assessment [ Time Frame: 24months ] [ Designated as safety issue: No ]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%).
|Study Start Date:||November 2011|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
|Experimental: RAD001 (everolimus)||
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.
Other Name: everolimus
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