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Clinical Trial Name - Vorinostat and Azacitidine in Treating Patients With Locally Recurrent or Metastatic Nasopharyngea
| Original Study ID : CDR0000472702 |
| Secondary ID : Array |
| NCT ID : NCT00336063 |
| Brief Title : Vorinostat and Azacitidine in Treating Patients With Locally Recurrent or Metastatic Nasopharyngeal Cancer or Nasal Natural Killer T-Cell Lymphoma |
| Official Title : A Phase I Trial of 5Azacitidine and Suberoylanilide Hydroxamic Acid in Patients With Metastatic or Locally Recurrent Nasopharyngeal Carcinoma and Nasal NK-T Cell Lymphoma |
| Brief Summary : RATIONALE: Drugs used in chemotherapy, such as vorinostat and azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Vorinostat and azacitidine also may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving vorinostat together with azacitidine may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat when given together with azacitidine in treating patients with locally recurrent or metastatic nasopharyngeal cancer or nasal natural killer T-cell lymphoma. |
| Source : National Cancer Institute (NCI) |
| Detailed Description : OBJECTIVES: Primary - Determine the dose-limiting toxicity of vorinostat (SAHA) in combination with azacitidine in patients with locally recurrent or metastatic nasopharyngeal carcinoma or nasal type natural killer (NK)/T-cell lymphoma. - Determine the maximum tolerated dose of SAHA given in combination with a fixed dose azacitidine in these patients, based on evidence of Epstein-Barr virus (EBV) lytic induction in tumor biopsies and plasma. Secondary - Assess the effect of SAHA on histone acetylation as measured in tumor and peripheral blood mononuclear cells of these patients. - Assess the effect of azacitidine on EBV promoter demethylation in these patients. - Study the effect of azacitidine on the pharmacokinetics of SAHA in these patients. OUTLINE: This is a multicenter, dose-escalation study of vorinostat (SAHA). Patients receive azacitidine subcutaneously on days 1-10 and oral SAHA twice daily on days 1-14. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease may continue treatment at the discretion of the principal investigator. Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Six patients are treated at the MTD. Patients undergo blood collection and tumor biopsies periodically during study for pharmacologic and biomarker correlative studies. PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study. |
| Overall Status : Recruiting |
| Start Date : March 2006 |
| Official Title : Phase 1 |
| Phase : Interventional |
| Study Design : Treatment |
| Enrollment : 18 |
| Verification Date : February 2008 |
| First Received Date : June 8, 2006 |
| Trial Eligibility |
| Criteria : DISEASE CHARACTERISTICS: - Biopsy proven nasopharyngeal carcinoma (WHO type 3) or extranodal nasal type natural killer (NK)/T-cell non-Hodgkin's lymphoma - Recurrence or metastases does not require tissue documentation - Meets 1 of the following staging criteria: - Locally recurrent disease - Treated with ≥ 1 chemotherapy regimen after relapse - Not amenable to surgical resection - Not amenable to further curative radiotherapy - Metastatic disease - Disease must be accessible for fine-needle aspiration biopsy - No clinical evidence of CNS involvement, including brain metastases or carcinomatous meningitis - Skull base involvement allowed PATIENT CHARACTERISTICS: - ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100% - Life expectancy > 6 months - WBC ≥ 3,000/mm³ - Absolute neutrophil count ≥ 1,500/mm³ - Platelet count ≥ 100,000/mm³ - Bilirubin ≤ 1.5 times upper limit of normal (ULN) - AST/ALT ≤ 2.5 times ULN (< 5 times ULN if liver metastases present) - PTT ≤ 1.5 times ULN - Albumin ≥ 2.7 g/dL - Creatinine ≤ 1.5 times ULN OR creatinine clearance > 50 mL/min - No uncontrolled intercurrent illness including, but not limited to, any of the following: - Ongoing or active infection - Symptomatic congestive heart failure - Unstable angina pectoris - Cardiac arrhythmia - Psychiatric illness or social situations that would limit study compliance - Not pregnant or nursing - Fertile patients must use effective contraception - Negative pregnancy test - No history of allergic reaction to compounds of similar chemical or biologic composition to azacitidine or vorinostat (SAHA) - No chronic active hepatitis B PRIOR CONCURRENT THERAPY: - See Disease Characteristics - At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy and recovered - At least 2 weeks since prior valproic acid - No more than 1 concurrent multivitamin daily - No concurrent prophylactic hematopoietic growth factors - No other concurrent investigational agents - No concurrent combination antiretroviral therapy for HIV-positive patients - No other concurrent anticancer agents or therapies - No other concurrent chemotherapy (including photopheresis), psoralen-ultraviolet treatment (PUVA), radiotherapy, or biologic therapy |
| Gender : Both |
| Minimum Age : 21 Years |
| Maximum Age : N/A |
| Healthy Volunteers : No |
| Facilities |
| Facility Name : Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
| Status : Recruiting |
| City : Baltimore |
| State : Maryland |
| Zip Code : 21231-2410 |
| Country : United States |
| Facility Name : Prince of Wales Hospital |
| Status : Recruiting |
| City : Shatin, New Territories |
| State : Maryland |
| Zip Code : 21231-2410 |
| Country : Hong Kong |
| Facility Name : Cancer Institute at National University Hospital |
| Status : Recruiting |
| City : Singapore |
| State : Maryland |
| Zip Code : 119074 |
| Country : Singapore |
| Facility Name : Johns Hopkins Singapore International Medical Centre |
| Status : Recruiting |
| City : Singapore |
| State : Maryland |
| Zip Code : 119074 |
| Country : Singapore |
| Facility Name : National Cancer Centre - Singapore |
| Status : Recruiting |
| City : Singapore |
| State : Maryland |
| Zip Code : 169610 |
| Country : Singapore |
| OutComes |
| Primary OutComes |
| Measure : Toxicity |
| Safety issue : Yes |
| Secondary OutComes |
| Measure : Pharmacokinetics |
| Safety issue : No |
| Interventions |
| Type : Drug |
| Name : azacitidine |
| Type : Drug |
| Name : vorinostat |
| Type : Other |
| Name : laboratory biomarker analysis |
| Type : Other |
| Name : pharmacological study |
| Type : Procedure |
| Name : biopsy |
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