Study of Vorinostat Plus Capecitabine (X) and Cisplatin (P) for 1st Line Treatment of Metastatic or Recurrent Gastric Cancer: Zolinza+XP

Study Overview
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Brief Summary
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There is scientific rationale for exploring the role of vorinostat, histone deacetylase inhibitor with capecitabine (X) and cisplatin (P), one of standard chemotherapy in patients with advanced gastric cancer. XP is a new standard of care in advanced gastric cancer (AGC) and vorinostat is a novel targeted agent that prevents tumor cell proliferation, survival and angiogenesis through histone deacetylase inhibition.

Official Title
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A Phase I/II Study of Vorinostat (Zolinza®) in Combination With Capecitabine (X) and Cisplatin (P) for 1st Line Treatment of Metastatic or Recurrent Gastric Cancer

Conditions
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Gastric Cancer, Histone Deacetylase Inhibitor

Intervention / Treatment
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* Drug: Vorinostat, capecitabine, and cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed unresectable or metastatic advanced gastric adenocarcinoma Completion of adjuvant chemotherapy 6 months before the study, or no previous chemotherapy Age 18 to 70 years old Eastern Cooperative Oncology Group (ECOG) performance status 2 or less Estimated life expectancy of more than 3 months Presence of measurable or evaluable disease Adequate bone marrow function (ANC >1,500/µL and platelets>100,000/µL), Adequate renal function: creatinine < 1 x upper normal limit (UNL) or creatinine clearance 60ml/min or less Adequate hepatic function: bilirubin < 1.5 x UNL, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels < 2.5 x UNL (< 5 x upper limit of normal for patients with liver involvement of their cancer), alkaline phosphatase < 5 x UNL (except in case of bone metastasis without any liver disease) Written informed consent Exclusion Criteria: Prior exposure to any histone deacetylase (HDAC) inhibitor (however, valproic acid would be allowed if a 30-day wash-off period is provided.) Previous adjuvant treatment with capecitabine or platinums Contraindication to any drug contained in the chemotherapy regimen Other tumor type than adenocarcinoma Presence or history of central nervous system (CNS) metastasis Gastric outlet or bowel obstruction Evidence of serious gastrointestinal bleeding Peripheral neuropathy > grade 2 History of significant neurologic or psychiatric disorders History of another malignancy within the last five years except cured basal cell carcinoma of skin and cured carcinoma in-situ of uterine cervix Pregnant or lactating women, women of childbearing potential not employing adequate contraception Active human immunodeficiency virus (HIV) infection Viral hepatitis infections Other serious illness or medical conditions

Ages Eligible for Study
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Minimum Age: 18 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: Vorinostat plus XP<br>Vorinostat 200 400mg per day on day1-day14 combined with capecitabine 800-1,000mg/m2/dose, BID on day1-day14, and cisplatin 60-80mg/m2 on day 1 | Drug: Vorinostat, capecitabine, and cisplatin<br>* Vorinostat 200 400mg per day on day1-day14 combined with capecitabine 800-1,000mg/m2/dose, BID on day1-day14, and cisplatin 60-80mg/m2 on day 1<br>* Other names: Zolinza, and xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 - maximum tolerated dose, Phase 2 - response rate |  | 3 weeks for maximum tolerated dose, and 6 months for response rate | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity profile |  | toxicity for each cycle | 
| Progression-free survival | Time from first administration of study drug to disease progression or any cause of death | 1 year | 
| Overall survival | Time from first administration of study drug to any cause of death | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastric cancer, histone deacetylase inhibitor, 1st line chemotherapy