NCT00635791已完成1 期
A Phase I Safety and Tolerability Study of Vorinostat in Combination With Sorafenib in Patients With Advanced Solid Tumors, With Exploration of Two Tumor-type Specific Expanded Cohorts at the Recommended Phase 2 Dose
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
This phase I trial studies the side effects and best dose of giving vorinostat and sorafenib tosylate together in treating patients with kidney or non-small cell lung cancer. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may stop the growth of solid tumors by blocking blood flow to the tumor. Giving vorinostat together with sorafenib tosylate may kill more tumor cells.
详细描述
The main purpose of this study is to:
- Evaluate the safety of vorinostat in combination with sorafenib.
- Determine the largest dose of vorinostat + sorafenib that can be given safely to humans.
- Determine if vorinostat + sorafenib are effective in stopping tumors from growing or in decreasing their size.
- Study the side effects of vorinostat + sorafenib.
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
- •Parts A: Histologically or cytologically documented solid tumor malignancy or non-Hodgkin's lymphoma (Part B: renal cell carcinoma, Part C: non-small cell lung carcinoma) with clinical evidence of advanced and/or metastatic disease, which is refractory to established forms of therapy or for which no effective therapy exists, or for which sorafenib alone would be considered by the investigator as an appropriate therapy; patients who have refused available standard therapies would also be deemed eligible
- •In Part A, evaluable disease by radiology and/or a recognized serum tumor marker is required; in Parts B and C, measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) is required
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
- •Predicted life expectancy ≥ 12 weeks
- •Patients may have had prior therapy, providing the following conditions are met:
- •Patients must have recovered from any treatment related toxicities (with the exception of alopecia) to ≤ CTC grade 1 (fatigue, and neurotoxicity at grade 2 are permissible if stable for > 3 months) prior to registration
- •Chemotherapy: A minimum of 5 predicted half-lives of the agent must have elapsed between the end of treatment and registration on to the study; when half-lives are not available the principle of 2 weeks for once daily medications and 3 weeks for agents given less frequently will be adopted, but discussion with the principal investigator is recommended
- •Hormonal therapy: Patients may have had prior anticancer hormonal therapy provided it is discontinued > 4 weeks prior to registration into the study; however, patients with prostate cancer with evidence of progressive disease may continue on therapy which produces medical castration (eg, goserelin or leuprorelin) provided this was commenced at least three months earlier
- •Radiation: Patients may have had prior radiation therapy that has not exceeded 25% of bone marrow reserve provided that they have recovered from the acute, toxic effects of radiotherapy prior to registration; a minimum of 7 days must have elapsed between the end of radiotherapy to non-target lesions and registration into the study (minimum of 28 days for target lesions)
- •Surgery: Previous surgery is permitted provided that wound healing has occurred prior to registration
- •Supportive therapy including bisphosphonates is permissible; previous use of myeloid and erythroid growth factor support is permissible, but not within 2 weeks of commencement of study; primary prophylactic use of myeloid and erythroid growth factors is not permitted within the study, but intervention or secondary prophylaxis is permitted if instituted following the documentation of ≥ grade 3 neutropenia or ≥ grade 2 anemia (hemoglobin)
- •International Normalized Ratio (INR) < 1.5 or a prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits; patients receiving anticoagulation treatment with an agent such as warfarin or heparin may be allowed to participate; for patients on warfarin, the INR should be measured prior to initiation of sorafenib/vorinostat and monitored at least weekly, or as defined by the local standard of care, until INR is stable; vorinostat and sorafenib have both been reported to elevate INR in those on coumadin derivatives
- •Neutrophil count ≥ 1.5 x 10^9/L
- •Platelet count ≥ 75 x 10^9/L
- •Bilirubin ≤ 1.5 x Upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) and/or alanine transaminase (ALT) ≤ 2.5 x ULN (ie, ≤ CTC grade 1) or ≤ 5 x Upper limit of normal (UNL) if patient has documented liver metastases (ie, ≤ CTC grade 2)
- •Serum creatinine ≤ 1.5 x ULN
- •Patient must be accessible for repeat dosing and follow-up
- •Patients - both males and females - with reproductive potential (ie, menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures throughout the study; women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration
- •Patients must provide verbal and written informed consent to participate in the study, including pharmacokinetic sampling
排除标准
- •Active or uncontrolled infections or serious illnesses or medical conditions that could interfere with the patient's ongoing participation in the study
- •History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent
- •Concurrent anticancer therapy (with the exception of hormonal therapies as discussed above)
- •Pregnant or breast-feeding females (documented methods of birth control are required in those with reproductive potential)
- •Symptomatic brain metastases which are not stable, require steroids, or anti-epileptic medication
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs
- •History of grade 3 or greater toxicities with vorinostat or sorafenib previously at equivalent daily doses or lower than those planned on being administered within this study
- •Exposure to other histone deacetylase (HDAC) inhibitors (e.g. sodium valproate) within 30 days of planned commencement of study drugs, other exposures to HDAC inhibitor and sorafenib in combination
- •Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management
- •Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
- •Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months
- •Pulmonary hemorrhage/bleeding event >= Common Toxicity Criteria for Adverse EffectS (CTCAE) grade 2 within 4 weeks of first dose of study drug
- •Any other hemorrhage/bleeding event >= CTCAE grade 3 within 4 weeks of first dose of study drug
- •Serious non-healing wound, ulcer, or bone fracture
- •Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug
- •Use of St. John's Wort or rifampin (rifampicin)
- •Known or suspected allergy to sorafenib, vorinostat or any planned agent given in the course of this trial
- •Any condition that impairs patient's ability to swallow whole pills
- •Any clinically significant malabsorption problem
- •Clinically significant, in the investigator's opinion, pre-existing cardiac dysfunction or myocardial infarction within 6 months prior to planned commencement of study drugs
- •Any other condition, which in the investigator's opinion, would compromise the safety of the patient or the feasibility of completing the study objectives through the use of this patient
研究组 & 干预措施
Sorafenib tosylate and vorinostat
Experimental
Patients receive sorafenib tosylate by mouth twice a day on days 1-21 and vorinostat by mouth every day on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Sorafenib (Drug)
Sorafenib tosylate and vorinostat
Experimental
Patients receive sorafenib tosylate by mouth twice a day on days 1-21 and vorinostat by mouth every day on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Vorinostat (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: Up to 21 days
The primary objective of this study is to determine the MTD for vorinostat in combination with the recommended dose of sorafenib 400 mg when given daily in a 21-day cycle and thereby establish a recommended Phase 2 dose of the combinations when administered daily in patients with advanced solid tumors
次要结局
未报告次要终点
研究者
研究点 (1)
Loading locations...
相似试验
已完成
1 期
Sorafenib and Vorinostat in Treating Patients With Advanced Liver CancerLiver CancerNCT01075113Virginia Commonwealth University16
已完成
1 期
Vorinostat and Doxorubicin in Treating Patients With Metastatic or Locally Advanced Solid TumorsUnspecified Adult Solid Tumor, Protocol SpecificNCT00331955National Cancer Institute (NCI)40
已完成
1 期
Vorinostat in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma and Liver DysfunctionAdult Grade III Lymphomatoid GranulomatosisAdult Nasal Type Extranodal NK/T-cell LymphomaAngioimmunoblastic T-cell LymphomaCutaneous B-cell Non-Hodgkin LymphomaExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueIntraocular LymphomaNodal Marginal Zone B-cell LymphomaPrimary Central Nervous System Hodgkin LymphomaPrimary Central Nervous System Non-Hodgkin LymphomaRecurrent Adult Burkitt LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Mixed Cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell LymphomaRecurrent Adult Grade III Lymphomatoid GranulomatosisRecurrent Adult Hodgkin LymphomaRecurrent Adult Immunoblastic Large Cell LymphomaRecurrent Adult Lymphoblastic LymphomaRecurrent Adult T-cell Leukemia/LymphomaRecurrent Cutaneous T-cell Non-Hodgkin LymphomaRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Mycosis Fungoides/Sezary SyndromeRecurrent Small Lymphocytic LymphomaSmall Intestine LymphomaSplenic Marginal Zone LymphomaStage III Adult Burkitt LymphomaStage III Adult Diffuse Large Cell LymphomaStage III Adult Diffuse Mixed Cell LymphomaStage III Adult Diffuse Small Cleaved Cell LymphomaStage III Adult Hodgkin LymphomaStage III Adult Immunoblastic Large Cell LymphomaStage III Adult Lymphoblastic LymphomaStage III Adult T-cell Leukemia/LymphomaStage III Cutaneous T-cell Non-Hodgkin LymphomaStage III Grade 1 Follicular LymphomaStage III Grade 2 Follicular LymphomaStage III Grade 3 Follicular LymphomaStage III Mantle Cell LymphomaStage III Marginal Zone LymphomaStage III Mycosis Fungoides/Sezary SyndromeStage III Small Lymphocytic LymphomaStage IV Adult Burkitt LymphomaStage IV Adult Diffuse Large Cell LymphomaStage IV Adult Diffuse Mixed Cell LymphomaStage IV Adult Diffuse Small Cleaved Cell LymphomaStage IV Adult Hodgkin LymphomaStage IV Adult Immunoblastic Large Cell LymphomaStage IV Adult Lymphoblastic LymphomaStage IV Adult T-cell Leukemia/LymphomaStage IV Cutaneous T-cell Non-Hodgkin LymphomaStage IV Grade 1 Follicular LymphomaStage IV Grade 2 Follicular LymphomaStage IV Grade 3 Follicular LymphomaStage IV Mantle Cell LymphomaStage IV Marginal Zone LymphomaStage IV Mycosis Fungoides/Sezary SyndromeStage IV Small Lymphocytic LymphomaUnspecified Adult Solid Tumor, Protocol SpecificWaldenström MacroglobulinemiaAnaplastic Large Cell LymphomaNCT00499811National Cancer Institute (NCI)15
已完成
1 期
Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous LeukemiaAdult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesAdult Acute Myeloid Leukemia With Inv(16)(p13;q22)Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)Blastic Phase Chronic Myelogenous LeukemiaExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueNodal Marginal Zone B-cell LymphomaRecurrent Adult Acute Lymphoblastic LeukemiaRecurrent Adult Acute Myeloid LeukemiaRecurrent Adult Burkitt LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Mixed Cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell LymphomaRecurrent Adult Immunoblastic Large Cell LymphomaRecurrent Adult Lymphoblastic LymphomaRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Small Lymphocytic LymphomaSecondary Acute Myeloid LeukemiaSplenic Marginal Zone LymphomaStage III Adult Burkitt LymphomaStage III Adult Diffuse Large Cell LymphomaStage III Adult Diffuse Mixed Cell LymphomaStage III Adult Diffuse Small Cleaved Cell LymphomaStage III Adult Immunoblastic Large Cell LymphomaStage III Adult Lymphoblastic LymphomaStage III Grade 1 Follicular LymphomaStage III Grade 2 Follicular LymphomaStage III Grade 3 Follicular LymphomaStage III Mantle Cell LymphomaStage III Marginal Zone LymphomaStage III Small Lymphocytic LymphomaStage IV Adult Burkitt LymphomaStage IV Adult Diffuse Large Cell LymphomaStage IV Adult Diffuse Mixed Cell LymphomaStage IV Adult Diffuse Small Cleaved Cell LymphomaStage IV Adult Immunoblastic Large Cell LymphomaStage IV Adult Lymphoblastic LymphomaStage IV Grade 1 Follicular LymphomaStage IV Grade 2 Follicular LymphomaStage IV Grade 3 Follicular LymphomaStage IV Mantle Cell LymphomaStage IV Marginal Zone LymphomaStage IV Small Lymphocytic LymphomaUnspecified Adult Solid Tumor, Protocol SpecificUntreated Adult Acute Lymphoblastic LeukemiaUntreated Adult Acute Myeloid LeukemiaNCT00275080National Cancer Institute (NCI)80
进行中（未招募）
1 期
Vorinostat and Temozolomide in Treating Patients With Malignant GliomasAdult Anaplastic AstrocytomaAdult Anaplastic OligodendrogliomaAdult Giant Cell GlioblastomaAdult GlioblastomaAdult GliosarcomaAdult Mixed GliomaRecurrent Adult Brain NeoplasmNCT00268385National Cancer Institute (NCI)83