RAD001 in Combination With Capecitabine and Oxaliplatin (XELOX) in Patients With Advanced Gastric Cancer: RAD001+XELOX

Study Overview
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Brief Summary
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It is expected that RAD001 works in gastric cancer by inhibiting PI3K/AKT/mTOR pathway and Hif1A (hypoxia inducible factor 1, alpha subunit), a key player in angiogenesis and the growth of tumors like renal cell carcinoma.However, RAD001 alone looks not enough to control gastric cancer. By the mechanisms above, RAD001 can show additive or synergistic effect in combination with conventional chemotherapy. In this study, XELOX was selected as a conventional combination chemotherapy because it was proven very active and safe in gastric cancer. Combination of XELOX and RAD001 has been never tried for the treatment of cancer patients yet. So, the optimal dose will be first determined in this phase I study

Detailed Description
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For the first cohort of this phase I study, each drug of capecitabine, oxaliplatin, and RAD001 will be started at one or two dose below the ordinary full dose of each drug as a single agent.

Official Title
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A Phase I Dose Finding Study of RAD001 in Combination With Capecitabine and Oxaliplatin (XELOX) in Patients With Advanced Gastric Cancer

Conditions
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Advanced Gastric Cancer

Intervention / Treatment
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* Drug: RAD001, Capecitabine, Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically documented unresectable or metastatic adenocarcinoma of stomach or gastroesophageal junction No history of chemotherapy or radiation Age 18 to 70 years old Estimated life expectancy of at least 3 months Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Adequate bone marrow function (white blood cell counts >3,000/uL, absolute neutrophil count>1,500/uL, Platelets>100,000/uL, Hgb>8 g/dL) Adequate kidney function (creatinine<1.5 mg/dL) Adequate liver function (bilirubin<1.5 mg/dL, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level <3 times the upper normal limit (5 times for patients with liver metastasis)) Signed written informed consent Exclusion Criteria: Past or concurrent history of neoplasm other than gastric adenocarcinoma except for curatively treated basal cell carcinoma of skin or in situ carcinoma of the cervix uteri Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start Presence of central nervous system metastasis Bowel obstruction Evidence of serious gastrointestinal bleeding Peripheral neuropathy (NCI CTC AE version 3.0 > Grade I) History of significant neurologic or psychiatric disorders Pregnant or lactating women, women of childbearing potential not employing adequate contraception Other serious illness or medical conditions Patients with known history of ischemic heart disease and/or with myocardial infarction Known allergy to study drugs Administration of drugs showing interaction with RAD001

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Xelox+RAD001<br> | Drug: RAD001, Capecitabine, Oxaliplatin<br>* Dose level -1 : Capecitabine 800mg/m2 po bid D1-14, Oxaliplatin 100mg/m2 iv D1 RAD001 5mg po qd D1-21 Dose level 1 : Capecitabine 800mg/m2 po bid D1-14, Oxaliplatin 100mg/m2 iv D1 RAD001 7.5mg po qd D1-21 Dose level 2 : Capecitabine 800mg/m2 po bid D1-14, Oxaliplatin 130mg/m2 iv D1 RAD001 7.5mg po qd D1-21 Dose level 3 : Capecitabine 1000mg/m2 po bid D1-14, Oxaliplatin 100mg/m2 iv D1 RAD001 7.5mg po qd D1-21 Dose level 3A : Capecitabine 800mg/m2 po bid D1-14, Oxaliplatin 130mg/m2 iv D1 RAD001 10mg po qd D1-21 Dose level 3B : Capecitabine 1000mg/m2 po bid D1-14, Oxaliplatin 100mg/m2 iv D1 RAD001 10mg po qd D1-21 Dose level 4 : Capecitabine 1000mg/m2 po bid D1-14, Oxaliplatin 130mg/m2 iv D1 RAD001 7.5mg po qd D1-21 Dose level 5 : Capecitabine 1000mg/m2 po bid D1-14, Oxaliplatin 130mg/m2 iv D1 RAD001 10mg po qd D1-21<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the maximum tolerated dose (MTD) |  | 1year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | 2 years | 
| Overall survival |  | 1 year | 
| Biomarker study |  | 1 year | 
| Response rate |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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XELOX, RAD001, phase 1