RAD001 in Advanced Gastric Cancer Who Failed Standard First-line Treatment With pS6 Ser 240/4 Expression

Sponsor

Asan Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT01482299

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Stomach Neoplasm	Drug: RAD001	Phase 2

Detailed Description

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 Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Nov 1, 2011

Actual Primary Completion Date :

Jan 1, 2014

Actual Study Completion Date :

Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RAD001 (everolimus)	Drug: RAD001 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 Names: everolimus

Arm

Intervention/Treatment

Experimental: RAD001 (everolimus)

Drug: RAD001

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 Names:

everolimus

Outcome Measures

Primary Outcome Measures

4-month progression-free survival [up to 3years]
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.

Secondary Outcome Measures

Response rate [Up to 1year]
evaluated with abdominal and pelvic dynamic CT scan every 8 weeks, using RECIST version 1.0
Number of participants with adverse events [Monitoring of adverse events will be contineud for at least 28days following the last dose of study treatment]
Adverse events will be graded according to Common Terminology Criteria for Adverse events version 4.0
Overall survival [Up to 3years]
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 [24months]
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%).

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

histologically or cytologically documented stomach adenocarcinoma including adenocarcinoma of the esophagogastric junction
non-resectable disease by metastasis or recurrent disease after curative surgical resection (See Appendix A) with uni-dimensionally measurable disease
failure of 1st line chemotherapy including fluoropyrimidine (capecitabine, S1, or 5-FU,) and platinum (cisplatin or oxaliplatin) in palliative setting; progression during or within 6 months after chemotherapy
High expression of pS6 Ser 240/4 (proportion of pS6 Ser 240/4 positive cancer cells by immunohistochemistry > 10%)
Age 20 to 75 years old
Estimated life expectancy of more than 3 months
ECOG performance status of 2 or lower
Adequate bone marrow function
Adequate kidney function
Adequate liver function
Fasting serum cholesterol ≤ 300 mg/dL AND fasting triglyceride ≤ 2.5 X ULN
No prior radiation therapy to more than 25% of BM
psychological, familial, sociological or geographical conditions which do not permit medical follow-up and compliance with this study
Women of childbearing potential must have a negative pregnancy test on admission
Written informed consent

Exclusion Criteria:

Other tumor type than adenocarcinoma
CNS metastases or prior radiation for CNS metastases
Gastric outlet obstruction or intestinal obstruction
Evidence of active gastrointestinal bleeding
Bone lesions as the sole evaluable disease
Past or concurrent history of neoplasm other than stomach cancer
Pregnant or lactating women, women of childbearing potential not employing adequate contraception
Other serious illness or medical conditions
Concomitant or with a 4-week period administration of any other experimental drug under investigation
Concomitant chemotherapy, hormonal therapy, or immunotherapy
Any preexisting medical condition of sufficient severity to prevent full compliance with the study