A Phase I Trial Of Vorinostat In The Treatment Of Advanced Laryngeal, Hypopharyngeal, Nasopharyngeal And Oropharyngeal Squamous Cell Carcinoma Of The Head And Neck.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose of vorinostat in combination with concurrent chemoradiation therapy
研究概览
简要总结
RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells. Giving vorinostat together with chemotherapy and radiation therapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat when given together with cisplatin and radiation therapy in treating patients with stage III or stage IVa squamous cell cancer of the oropharynx which is either unresectable or borderline resectable.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximally tolerated dose of Vorinostat in combination with concurrent chemoradiotherapy for the treatment of advance stage OPSCC.
SECONDARY OBJECTIVES:
l. To determine the complete response rate, overall survival and progression free survival using the maximally tolerated dose of Vorinostat.
TERTIARY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically confirmed unresectable or borderline resectable squamous cell carcinoma of the oropharynx will be eligible for enrollment to the clinical trial
- •Oropharyngeal sites of tumor include tonsil, soft palate, base of tongue, lateral and posterior pharyngeal wall
- •Patient must be AJCC (American Joint Committee on Cancer) Stage III (T3N0, T1-2N1) or Stage IVa (T1-4N2-3M0, T4N0-1 M0) and be either unresectable or borderline resectable
- •No prior therapy for the tumor, including extensive surgery, radiation therapy, chemotherapy, immunotherapy, targeted therapy or any other investigational agents; surgical biopsy prior to beginning the study is allowable
- •Prior malignancies at sites other than the head and neck are allowable if there has been greater than or equal to a 3 year disease free interval; basal cell carcinoma of the skin and in-situ cervix dysplasias are allowable within this 3 year interval if completely resected
- •There must be documentation of evaluable tumor within four weeks of beginning therapy
- •ECOG (Eastern Cooperative Oncology Group) Performance Status 0-2, (Karnofsky > 60%)
- •Ability to understand and the willingness to sign a written informed consent
- •Patient must have normal liver and bone marrow function
- •Absolute neutrophil count (ANC) >= 1,500/mcL
- •Platelets >= 100,000/mcL
- •Hemoglobin >= 9 g/dL
- •Prothrombin Time or INR (international normalized ratio) =< 1.5x upper limit of normal (ULN) unless receiving therapeutic anticoagulation
- •Partial thromboplastin time (PTT) =< 1.2 times the ULN unless the patient is receiving therapeutic anticoagulation
- •K levels preferred normal limits with no clinical abnormalities
- •Mg levels preferred normal limits with no clinical abnormalities
- •Creatinine =< ULN OR Calculated creatinine clearance >= 50 mL/min
- •Serum total bilirubin =< 1.5 X ULN
- •AST (SGOT) and ALT (SGPT) =< 2.5 X ULN
- •Alkaline Phosphatase =< 2.5 X ULN
- •No known malabsorption syndrome
- •Female patients of childbearing potential must be willing to use birth control; the 2 birth control methods can be either 2 barrier methods or a barrier method plus a hormonal method to prevent pregnancy, used throughout the study starting with visit 1
- •The following are considered adequate barrier methods of contraception: diaphragm, condom (by the partner) or sponge; other methods of contraception such as copper intrauterine device or spermicide may be used
- •Appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular agents); female patient of childbearing potential has a negative serum pregnancy test β-hCG within 7 days prior to receiving the first dose of vorinostat
- •Male patients agree to use an adequate method of contraception for the duration of the study
- •The patient must have a life expectancy of at least 12 weeks
- •Patients on coumadin therapy are eligible for study
排除标准
- •Major surgery or trauma occurring within 28 days of starting the trial
- •History of allergic reactions attributed to compounds similar in chemical or biological composition to Vorinostat or other agents used in this study
- •Gastrointestinal tract disease or previous surgical procedures resulting in an inability to take oral or enteral medication or a requirement for IV alimentation
- •Pregnant women; breast feeding should be discontinued during treatment
- •Active peptic ulcer disease
- •Uncontrolled comorbid illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina, untreated or new cardiac arrhythmia, psychiatric or social condition which would limit the patient's understanding of and compliance with the study
- •Prisoners and other vulnerable populations
- •Patients who have had prior treatment with an HDAC inhibitor (e.g., romidepsin (Depsipeptide), NSC-630176, MS 275, LAQ-824, belinostat (PXD-101), LBH589, MGCD0103, CRA024781, etc)
- •Patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study; patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period
- •Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drug(s)
- •Patients with known active viral hepatitis or known HIV infection
研究组 & 干预措施
Arm I
Patients receive oral vorinostat on days 0-2 and cisplatin IV on days 7, 21 and 35. Patients undergo radiation therapy 5 days a week beginning on day 7. Patients also receive concurrent oral vorinostat along with the radiotherapy to be given 3 days per week (Monday, Tuesday, and Wednesday). Optional repeat tumor and normal mucosal biopsies will be performed and blood will be drawn for correlative studies.
干预措施: vorinostat (Drug)
Arm I
Patients receive oral vorinostat on days 0-2 and cisplatin IV on days 7, 21 and 35. Patients undergo radiation therapy 5 days a week beginning on day 7. Patients also receive concurrent oral vorinostat along with the radiotherapy to be given 3 days per week (Monday, Tuesday, and Wednesday). Optional repeat tumor and normal mucosal biopsies will be performed and blood will be drawn for correlative studies.
干预措施: cisplatin (Drug)
Arm I
Patients receive oral vorinostat on days 0-2 and cisplatin IV on days 7, 21 and 35. Patients undergo radiation therapy 5 days a week beginning on day 7. Patients also receive concurrent oral vorinostat along with the radiotherapy to be given 3 days per week (Monday, Tuesday, and Wednesday). Optional repeat tumor and normal mucosal biopsies will be performed and blood will be drawn for correlative studies.
干预措施: radiation therapy (Radiation)
Arm I
Patients receive oral vorinostat on days 0-2 and cisplatin IV on days 7, 21 and 35. Patients undergo radiation therapy 5 days a week beginning on day 7. Patients also receive concurrent oral vorinostat along with the radiotherapy to be given 3 days per week (Monday, Tuesday, and Wednesday). Optional repeat tumor and normal mucosal biopsies will be performed and blood will be drawn for correlative studies.
干预措施: Correlative Studies (Procedure)
结局指标
主要结局
Maximum tolerated dose of vorinostat in combination with concurrent chemoradiation therapy
时间窗: Weekly during treatment; Every 2 weeks for the first month after treatment completion; Then every 4 weeks until day 153
The toxic effects of the combination of vorinostat and cisplatin using NCI CTCAE v. 4.0
时间窗: Weekly during treatment; Every 2 weeks for the first month after treatment completion; Then every 4 weeks until day 153
次要结局
- Tumor responses to vorinostat or vorinostat combined with chemoradiation.(Days 35, 56 then after Day 153 every 12 weeks for 24 months)
- Progression free survival(Days 35, 56 then after Day 153 every 12 weeks for 24 months)
- Complete response rate(Days 35, 56 then after Day 153 every 12 weeks for 24 months)
- Overall survival(Days 35, 56 then after Day 153 every 12 weeks for 24 months)
- Relationship between Vorinostat therapy and tumor suppressor genes product assessed by Fas and FasL protein expression level in tumor and the normal mucosa(Before, post SAHA treatment, and post the concurrent chemoradiation /SAHA therapy)
- HPV-specific T-cell in patients with HPV+ tumors(After the run in period of vorinostat but before the start of RT; Day 35; 2 weeks after the completion of RT; Day 153)
研究者
Matthew Old
Principal Investigator
Ohio State University Comprehensive Cancer Center