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

Gastric Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01045538
• Other study ID #: AMC0903
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 2010
• Est. completion date: April 2016

Study information

• Verified date: January 2020
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: April 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Gastric Cancer
• Histone Deacetylase Inhibitor
• Stomach Neoplasms

Intervention

Drug:
• Vorinostat, capecitabine, and cisplatin
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

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (12)

Budman DR, Meropol NJ, Reigner B, Creaven PJ, Lichtman SM, Berghorn E, Behr J, Gordon RJ, Osterwalder B, Griffin T. Preliminary studies of a novel oral fluoropyrimidine carbamate: capecitabine. J Clin Oncol. 1998 May;16(5):1795-802. — View Citation

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. — View Citation

Glimelius B, Ekström K, Hoffman K, Graf W, Sjödén PO, Haglund U, Svensson C, Enander LK, Linné T, Sellström 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. — View Citation

Hansen RM. 5-Fluorouracil by protracted venous infusion: a review of recent clinical studies. Cancer Invest. 1991;9(6):637-42. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Kurdistani SK. Histone modifications as markers of cancer prognosis: a cellular view. Br J Cancer. 2007 Jul 2;97(1):1-5. Epub 2007 Jun 26. Review. — View Citation

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. — View Citation

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. — View Citation

Weichert W, Röske A, Gekeler V, Beckers T, Ebert MP, Pross M, Dietel M, Denkert C, Röcken 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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1 - maximum tolerated dose, Phase 2 - response rate		3 weeks for maximum tolerated dose, and 6 months for response rate
Secondary	Toxicity profile		toxicity for each cycle
Secondary	Progression-free survival	Time from first administration of study drug to disease progression or any cause of death	1 year
Secondary	Overall survival	Time from first administration of study drug to any cause of death	1 year