RAD001 (Everolimus) Salvage Monotherapy in Advanced Gastric Cancer (AGC) Who Failed Standard First-line Treatment

Study Overview
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Brief Summary
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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, and overall survival (secondary end-points) in patients with metastatic and/or advanced inoperable gastric cancer. Eligibility criteria include histologically proven gastric/gastroesophageal junction cancer who failed previous first-line standard treatment with fluoropyrimidine and platinum-based chemotherapy. 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. Total of 54 patients will be enrolled to decide whether the proportion of patients who are free from progression at 4 months (16 weeks), P, is less that or equal to 0.15 or greater than or equal to 0.30 to assess the treatment outcome in 48 patients assuming drop-out rate, 10%.

Official Title
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A Phase II Study of RAD001 (Everolimus) in Patients With Fluoropyrimidine and Platinum-refractory Advanced Gastric Cancer

Conditions
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Stomach Neoplasm

Intervention / Treatment
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* Drug: RAD001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically documented stomach adenocarcinoma including adenocarcinoma of the esophagogastric junction Patients must have non-resectable disease by metastasis or recurrent disease after curative surgical resection with uni-dimensionally measurable disease (at least longest diameter 1 cm on computed tomography scan, or at least 2 cm on chest x-ray or physical examination) Patients tumor should have failure of 1st line chemotherapy including fluoropyrimidine (5-FU, capecitabine, doxifluridine, S1, or UFT) and platinum (cisplatin, carboplatin, or oxaliplatin) in palliative setting; progression during or within 6 months after chemotherapy Age 18 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 No prior radiation therapy to more than 25 percent of BM Patients must not have 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 The patient must be able to understand the study and has given written informed consent to participate in the study Exclusion Criteria: Other tumor types than adenocarcinoma Central nervous system metastases or prior radiation for CNS metastasis Gastric outlet obstruction or intestinal obstruction Evidence of active gastrointestinal bleeding Bony metastasis 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 Thyroid disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Treatment Arm (RAD001) | Drug: RAD001<br>* RAD001 (everolimus) 10mg daily administration orally until disease progression and/or intolerability<br>* Other names: everolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival Rate at 4-month (16 Weeks) | progression is definced as a more than 20% increase in one or more lesions or the appearance of any new lesion | 4 months (16 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Tumor response is evaluated according to the new guidelines by RECIST criteria (See Appendix D). A complete response (CR) is defined as the disappearance of all evidence of cancer for 4 weeks or longer. A partial response (PR) is defined as a 30% or more reduction in the sum of the longest diameters of target lesions for 4 weeks or longer without any evidence of new lesions or progression of any lesions. Stable disease is defined as less than a 30% reduction or less than a 20% increase in the longest diameters of target lesions without any evidence of new lesions. Progressive disease is defined as a more than 20% increase in one or more lesions or the appearance of any new lesion. | 2years | 
| Overall Survival |  | 1 year | 
| Number of Participants With Adverse Events | (according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0) | up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RAD001 (everolimus), second-line treatment, advanced gastric cancer