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

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

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%.

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