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

Phase 2

Completed

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, 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%.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
1	RAD001	Treatment Arm (RAD001)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Response Rate	2years	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.
Overall Survival	1 year
Number of Participants With Adverse Events	up to 24 weeks	(according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0)