Back to resultsRAD001 in Advanced Gastric Cancer Who Failed Standard First-line Treatment With pS6 Ser 240/4 Expression
Primary Purpose
Stomach Neoplasm
Status
Completed
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
RAD001
Sponsored by
About this trial
This is an interventional treatment trial for Stomach Neoplasm focused on measuring pS6 Ser 240/4, RAD001 (everolimus), second-line treatment, advanced gastric cancer
Eligibility Criteria
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
Sites / Locations
- Asan Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
RAD001 (everolimus)
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Response rate
evaluated with abdominal and pelvic dynamic CT scan every 8 weeks, using RECIST version 1.0
Number of participants with adverse events
Adverse events will be graded according to Common Terminology Criteria for Adverse events version 4.0
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.
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%).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01482299
Brief Title
RAD001 in Advanced Gastric Cancer Who Failed Standard First-line Treatment With pS6 Ser 240/4 Expression
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 Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
January 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Asan Medical Center
4. Oversight
Data Monitoring Committee
No
5. 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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stomach Neoplasm
Keywords
pS6 Ser 240/4, RAD001 (everolimus), second-line treatment, advanced gastric cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RAD001 (everolimus)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
RAD001
Other Intervention Name(s)
everolimus
Intervention Description
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.
Primary Outcome Measure Information:
Title
4-month progression-free survival
Description
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
Secondary Outcome Measure Information:
Title
Response rate
Description
evaluated with abdominal and pelvic dynamic CT scan every 8 weeks, using RECIST version 1.0
Time Frame
Up to 1year
Title
Number of participants with adverse events
Description
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
Title
Overall survival
Description
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
Title
Biomarker assessment
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yoon-Koo Kang, MD, PhD
Organizational Affiliation
Asan Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Asan Medical Center
City
Songpa-gu
State/Province
Seoul
Country
Korea, Republic of
12. IPD Sharing Statement
Learn more about this trial
RAD001 in Advanced Gastric Cancer Who Failed Standard First-line Treatment With pS6 Ser 240/4 Expression
We'll reach out to this number within 24 hrs