NCT01005797已完成1 期
A Phase I Safety and Tolerability Study of LBH589 in Combination With Sorafenib in Patients With Advanced Renal Cell Carcinoma, Soft Tissue Sarcoma, and Non-small Cell Lung Carcinoma (NSCLC) of Non-squamous Histologies.
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
- 38
- 试验地点
- 1
- 主要终点
- Determine maximum tolerated dose (MTD)for LBH 589 in combination with Sorafenib and establish a recommended phase 2 dose for each drug combination
研究概览
简要总结
The purpose of this study is to determine if a new investigational drug called Panobinostat is safe, tolerable and to obtain an initial assessment of efficacy, when given in combination with Sorafenib for the treatment of certain types of lung cancer, kidney cancer and soft tissue sarcoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- •Male or female patients aged ≥ 18 years old
- •ECOG Performance Status of ≤ 2
- •Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
- •Part A (dose escalation): Histologically or cytologically documented metastatic renal cell carcinoma (RCC) of all histologic types, soft tissue sarcoma (STS) limited to the following histologies: angiosarcoma, liposarcoma, and leiomyosarcoma, or non-squamous non-small-cell lung carcinoma (NSCLC). Parts B (RCC) and C (NSCLC) and D (STS)(expanded cohorts). Patients with RCC must have progressive metastatic disease and received at least one multi-kinase inhibitor (e.g., sorafenib/Nexavar or sunitinib/Sutent), or an mTOR inhibitor (e.g., Temsirolimus). Patients with STS must have progressive disease and have received at least two therapeutic regimens (first-line, second-line treatments).
- •For patients with metastatic NSCLC, they must have received two standard therapeutic regimens (first-line and second-line treatments).
- •In Part A, evaluable disease by radiology and/or a recognized serum tumor marker is required. In Parts B, C, and D measurable disease by RECIST is required
- •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 halflives 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.
- •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.
- •Patients must meet the following laboratory criteria:
- •Hematology:
- •Neutrophil count of >1500/mm3
- •Platelet count of > 100,000/mm3L
- •Hemoglobin ≥ 9 g/dL
- •Biochemistry:
- •AST/SGOT and ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to disease involvement
- •Serum bilirubin ≤ 1.5 x ULN
- •Serum creatinine ≤ 2.0 x ULN or 24-hour creatinine clearance ≥ 50 ml/min
- •Total serum calcium (corrected for serum albumin) or ionized calcium ≥ LLN
- •Serum potassium ≥ LLN
- •Serum sodium ≥ LLN
- •Serum albumin ≥ LLN or 2.5 g/dl
- •Patients with any elevated Alkaline Phosphatase due to bone metastasis can be enrolled
- •INR < 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation 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/LBH589 and monitored at least weekly, or as defined by the local standard of care, until the INR is stable. LBH589 and sorafenib may elevate the INR in those on coumadin derivatives
- •Patients must be clinically euthyroid (patients may be on thyroid hormone replacement)'
- •Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal
- •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)
- •Patient must be accessible for repeat dosing and follow-up
- •Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of study treatment. and must be willing to use two methods of contraception one of them being a barrier method during the study and for 3 months after last study drug administration
- •Exclusion criteria:
- •NSCLC of squamous histology.
- •Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
- •Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment
- •Known or suspected allergy to sorafenib or LBH589
- •Impaired cardiac function including any one of the following:
- •Screening ECG with a QTc > 450 msec prior to enrollment to the study
- •Patients with congenital long QT syndrome
- •History of sustained ventricular tachycardia
- •Any history of ventricular fibrillation or torsades de pointes
- •Bradycardia defined as heart rate < 50 beats per minute. Patients with a pacemaker and heart rate ≥ 50 beats per minute are eligible.
- •Patients with a myocardial infarction or unstable angina within 6 months of study entry
- •Congestive heart failure (NY Heart Association class III or IV)
- •Right bundle branch block and left anterior hemiblock (bifasicular block)
- •Uncontrolled hypertension
- •Concomitant use of drugs with a risk of causing torsades de pointes (See Appendix 1.-1)
- •Concomitant use of CYP3A4 inhibitors (See Appendix 1.-2)
- •Patients with unresolved diarrhea > CTCAE grade 1
- 另有 20 项未显示
排除标准
- 未提供
研究组 & 干预措施
Expansion A
Experimental
Expansion A -RCC cohort expansion phase at RP2D: Sorafenib bid daily continuously from cycle 1 (28 day cycle), LBH589 given on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26 of a 28 day cycle.
干预措施: Panobinostat (LBH589), Sorafenib (Drug)
Expansion B
Experimental
Expansion B -NSCLC cohort expansion phase at RP2D: Sorafenib bid daily continuously from cycle 1 (28 day cycle), LBH589 given on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26 of a 28 day cycle.
干预措施: Panobinostat (LBH589), Sorafenib (Drug)
Expansion C
Experimental
Expansion C -STS cohort expansion phase at RP2D: Sorafenib bid daily continuously from cycle 1 (28 day cycle), LBH589 on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26 of a 28 day cycle.
干预措施: Panobinostat (LBH589), Sorafenib (Drug)
结局指标
主要结局
Determine maximum tolerated dose (MTD)for LBH 589 in combination with Sorafenib and establish a recommended phase 2 dose for each drug combination
时间窗: Point in time when no more than 1 of 6 patients has a Dose Limiting Toxicity (DLT) in cycle 1
次要结局
- Evaluate the safety profile of LGB589 in combination with sorafenib, including DLTs(During the first treatment period (i.e. 28 days) or toxicity similar to DLT after the initial 28-day treatment period)
- Observe evidence of anti-cancer efficacy estimates of the combination in the tarted expanded cohorts.(Evaluation of disease & re-evaluation for response)
研究者
研究点 (1)
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