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

NCT01045538 | Completed Phase 1 DMC

• 1 other identifier: AMC0903
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gastric Cancer; Histone Deacetylase Inhibitor

Keywords

gastric cancer; histone deacetylase inhibitor; 1st line chemotherapy

Outcome Measures

Primary Outcomes (1)

• Phase 1 - maximum tolerated dose, Phase 2 - response rate

  3 weeks for maximum tolerated dose, and 6 months for response rate

Secondary Outcomes (3)

• Toxicity profile

  toxicity for each cycle

• Progression-free survival

  1 year

• Overall survival

  1 year

Study Arms (1)

Vorinostat plus XP

EXPERIMENTAL

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

Interventions

Vorinostat, capecitabine, and cisplatin DRUG

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

Also known as: Zolinza, and xeloda

Vorinostat plus XP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center

Seoul, 138-736, South Korea

Location

Related Publications (12)

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  PMID: 9586893 BACKGROUND

• Cassidy J, Dirix L, Bissett D, Reigner B, Griffin T, Allman D, Osterwalder B, Van Oosterom AT. A Phase I study of capecitabine in combination with oral leucovorin in patients with intractable solid tumors. Clin Cancer Res. 1998 Nov;4(11):2755-61.

  PMID: 9829739 BACKGROUND

• Glimelius B, Ekstrom K, Hoffman K, Graf W, Sjoden PO, Haglund U, Svensson C, Enander LK, Linne T, Sellstrom H, Heuman R. Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol. 1997 Feb;8(2):163-8. doi: 10.1023/a:1008243606668.

  PMID: 9093725 BACKGROUND

• Hansen RM. 5-Fluorouracil by protracted venous infusion: a review of recent clinical studies. Cancer Invest. 1991;9(6):637-42. doi: 10.3109/07357909109039875.

  PMID: 1747791 BACKGROUND

• Hong YS, Song SY, Lee SI, Chung HC, Choi SH, Noh SH, Park JN, Han JY, Kang JH, Lee KS, Cho JY. A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann Oncol. 2004 Sep;15(9):1344-7. doi: 10.1093/annonc/mdh343.

  PMID: 15319239 BACKGROUND

• Kim NK, Park YS, Heo DS, Suh C, Kim SY, Park KC, Kang YK, Shin DB, Kim HT, Kim HJ, et al. A phase III randomized study of 5-fluorouracil and cisplatin versus 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil alone in the treatment of advanced gastric cancer. Cancer. 1993 Jun 15;71(12):3813-8. doi: 10.1002/1097-0142(19930615)71:123.0.co;2-5.

  PMID: 8508349 BACKGROUND

• Kim TW, Kang YK, Ahn JH, Chang HM, Yook JH, Oh ST, Kim BS, Lee JS. Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced gastric cancer. Ann Oncol. 2002 Dec;13(12):1893-8. doi: 10.1093/annonc/mdf323.

  PMID: 12453857 BACKGROUND

• Koizumi W, Saigenji K, Ujiie S, Terashima M, Sakata Y, Taguchi T; Clinical Study Group of Capecitabine. A pilot phase II study of capecitabine in advanced or recurrent gastric cancer. Oncology. 2003;64(3):232-6. doi: 10.1159/000069313.

  PMID: 12697963 BACKGROUND

• Kurdistani SK. Histone modifications as markers of cancer prognosis: a cellular view. Br J Cancer. 2007 Jul 2;97(1):1-5. doi: 10.1038/sj.bjc.6603844. Epub 2007 Jun 26.

  PMID: 17592497 BACKGROUND

• Mann BS, Johnson JR, Cohen MH, Justice R, Pazdur R. FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist. 2007 Oct;12(10):1247-52. doi: 10.1634/theoncologist.12-10-1247.

  PMID: 17962618 BACKGROUND

• Park YS, Jin MY, Kim YJ, Yook JH, Kim BS, Jang SJ. The global histone modification pattern correlates with cancer recurrence and overall survival in gastric adenocarcinoma. Ann Surg Oncol. 2008 Jul;15(7):1968-76. doi: 10.1245/s10434-008-9927-9. Epub 2008 May 10.

  PMID: 18470569 BACKGROUND

• Weichert W, Roske A, Gekeler V, Beckers T, Ebert MP, Pross M, Dietel M, Denkert C, Rocken C. Association of patterns of class I histone deacetylase expression with patient prognosis in gastric cancer: a retrospective analysis. Lancet Oncol. 2008 Feb;9(2):139-48. doi: 10.1016/S1470-2045(08)70004-4.

  PMID: 18207460 BACKGROUND

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Vorinostat; Capecitabine; Cisplatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 6, 2010
• First Posted: January 11, 2010
• Study Start: February 1, 2010
• Primary Completion: February 1, 2016
• Study Completion: April 1, 2016
• Last Updated: January 7, 2020

Record last verified: 2020-01

Locations

KR (1)