NCT01938833终止1 期
A Phase I/II Study of Romidepsin in Combination With Abraxane in Patients With Metastatic Inflammatory Breast Cancer
Sidney Kimmel Cancer Center at Thomas Jefferson University1 个研究点 分布在 1 个国家目标入组 9 人开始时间: 2014年4月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Maximum-Tolerated Dose of Romidepsin (Phase I)
研究概览
简要总结
This phase I/II trial studies the side effects and best dose of romidepsin when given together with paclitaxel albumin-stabilized nanoparticle formulation and to see how well they work in treating patients with metastatic inflammatory breast cancer. Romidepsin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving romidepsin and paclitaxel albumin-stabilized nanoparticle formulation may be an effective treatment for inflammatory breast cancer.
详细描述
PRIMARY OBJECTIVES:
- To assess the safety of the combination of romidepsin plus Abraxane (paclitaxel albumin-stabilized nanoparticle formulation) delivered weekly. (Phase I)
- To determine the maximum tolerated dose (MTD) of romidepsin with full dose weekly Abraxane to define a recommended phase II doses of the combination. (Phase I)
- To assess the progression-free survival (PFS) in patients with human epidermal growth factor receptor 2 (HER2) negative, newly diagnosed metastatic inflammatory breast cancer treated with the combination of romidepsin and Abraxane. (Phase II)
SECONDARY OBJECTIVES:
- To assess the safety and tolerability of the combination of romidepsin and Abraxane.
- To determine the adverse event profile of the combination of romidepsin and Abraxane.
- To assess the overall response rate (ORR) and clinical benefit rate (CBR) in patients with newly recurrent inflammatory breast cancer (IBC) treated with the combination of romidepsin and Abraxane.
OUTLINE: This is a phase I, dose-escalation study of romidepsin followed by a phase II study.
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 must have histologically or cytologically confirmed breast carcinoma with a clinical diagnosis of IBC based on the presence of inflammatory changes in the involved breast, such as diffuse erythema and edema (peau d'orange), with or without an underlying palpable mass involving the majority of the skin of the breast. Pathological evidence of dermal lymphatic invasion should be noted but is not required for diagnosis.
- •Patients may have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v. 1.1 as described in detail in section 11.0 or non-measurable tumors
- •Patients must have demonstrated metastatic disease and not received >2 lines of systemic therapy for metastatic disease
- •Age > 18 years
- •ECOG performance status 0, 1 or 2
- •Patients must have normal organ and marrow function as defined below: a) Leukocytes > 2,500/mcL b) Absolute neutrophil count > 1,500/mcL c) Hemoglobin > 9 g/dl d) Platelets > 100,000/mcL e) Total bilirubin < 1.5 mg/dl f) AST/ALT (SGOT/SGPT) < 2.5 x ULN g) Alkaline Phosphatase < 2.5 x ULN (unless bone metastasis is present in the absence of liver metastasis, in which case 3.0 x ULN would be acceptable. h) Serum magnesium > 1.8 mg/dL i) Serum creatinine < 1.5 mg/dl j) Serum potassium > 3.8 mmol/L
- •Tumor negative for HER2 expression (0 or 1+ by IHC) or negative FISH testing
- •Patients must have a life expectancy of at least 12 weeks
- •Patients must be recovered from the effects of any prior surgery, radiotherapy, or other antineoplastic therapy
- •Patients must have < Grade 2 pre-existing peripheral neuropathy per CTCAE
- •Women of childbearing potential and sexually active males must use an effective contraception method during treatment and for three months after completing treatment
- •Negative serum or urine β-hCG pregnancy test at screening, performed no more than 72 hours prior to treatment initiation; for patients of childbearing potential
- •Ability to understand and willingness to sign a written informed consent and HIPAA consent document
排除标准
- •Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse event from agents administered more than 4 weeks earlier
- •Patients may not be receiving any other investigational agents or active anti-neoplastic therapies
- •Patients who have previously received romidepsin or Abraxane
- •Patients with untreated or uncontrolled brain metastases or leptomeningeal disease
- •Patients with known hypersensitivity to any of the components of romidepsin or who have had hypersensitivity reactions to paclitaxel
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Any known cardiac abnormalities such as:
- •Congenital long QT syndrome
- •QTc interval ≥ 500 milliseconds
- •Myocardial infarction within 6 months of C1D
- •Subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate
- •Other significant EKG abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
- •Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV (see Appendix III) In any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present
- •An EKG recorded at screening showing evidence of cardiac ischemia (ST depression depression of ≥2 mm, measured from isoelectric line to the ST segment). If in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present
- •Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions (see Appendix IV) and/or known ejection fraction <40% by MUGA or <50% by echocardiogram and/orMRI
- •A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)
- •Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes
- •Uncontrolled hypertension, i.e., blood pressure (BP) of ≥ 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria
- •Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
- •Patients taking drugs leading to significant QT prolongation (See Appendix I: Medications That May Cause QTc Prolongation)
- •Concomitant use of CYP3A4 inhibitors (see Appendix II)
- •Patients with known HIV, hepatitis B or C (However, if patients have previously been treated for hepatitis B or C and have undetectable viral loads, they can be considered eligible for trial)
- •Pregnant or breast feeding. Refer to section 4.4 for further detail
- •Patients with any other medical or psychological condition deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
研究组 & 干预措施
Treatment (Romidepsin and Abraxane)
Experimental
Patients receive abraxane IV over 30 minutes and romidepsin IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Romidepsin (Drug)
Treatment (Romidepsin and Abraxane)
Experimental
Patients receive abraxane IV over 30 minutes and romidepsin IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Abraxane (Drug)
结局指标
主要结局
Maximum-Tolerated Dose of Romidepsin (Phase I)
时间窗: 28 days
Determined according to incidence of dose-limiting toxicity, graded using the National Cancer Institute (NCI) CTCAE version 4.0
Progression-Free Survival (PFS)
时间窗: The duration of time from start of treatment to time of progression or death, whichever occurs first, assessed up to 5 years
次要结局
- Incidence of Adverse Events, Graded According to NCI CTCAE Version 4.0(Up to 30 days)
- Clinical Benefit Rate (CBR)(Up to 5 years)
- Overall Response Rate (ORR)(Up to 5 years)
研究者
研究点 (1)
Loading locations...
相似试验
撤回
1 期
Rituximab, Romidepsin, and Lenalidomide in Treating Patients With Recurrent or Refractory B-cell Non-Hodgkin LymphomaB-cell Adult Acute Lymphoblastic LeukemiaExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueIntraocular LymphomaNodal Marginal Zone B-cell LymphomaRecurrent Adult Acute Lymphoblastic LeukemiaRecurrent 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 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 LymphomaRefractory Hairy Cell LeukemiaSmall Intestine LymphomaSplenic Marginal Zone LymphomaTesticular LymphomaWaldenström MacroglobulinemiaNCT02281279Mayo Clinic
已完成
1 期
Romidepsin, Ifosfamide, Carboplatin, and Etoposide in Treating Participants With Relapsed or Refractory Peripheral T-Cell LymphomaMycosis FungoidesRecurrent Anaplastic Large Cell LymphomaRecurrent Angioimmunoblastic T-Cell LymphomaRecurrent Enteropathy-Associated T-Cell LymphomaRecurrent Hepatosplenic T-Cell LymphomaRecurrent Peripheral T-Cell Lymphoma, Not Otherwise SpecifiedRefractory Anaplastic Large Cell LymphomaRefractory Angioimmunoblastic T-Cell LymphomaRefractory Enteropathy-Associated T-Cell LymphomaRefractory Hepatosplenic T-Cell LymphomaRefractory Peripheral T-Cell Lymphoma, Not Otherwise SpecifiedNCT01590732M.D. Anderson Cancer Center22
已完成
1 期
Romidepsin and Parsaclisib for the Treatment of Relapsed or Refractory T-Cell LymphomasRecurrent Anaplastic Large Cell LymphomaRecurrent Mature T-Cell and NK-Cell Non-Hodgkin LymphomaRecurrent Primary Cutaneous T-Cell Non-Hodgkin LymphomaRecurrent Transformed Mycosis FungoidesRefractory Anaplastic Large Cell LymphomaRefractory Mature T-Cell and NK-Cell Non-Hodgkin LymphomaRefractory Primary Cutaneous T-Cell Non-Hodgkin LymphomaRefractory Transformed Mycosis FungoidesT-Cell Non-Hodgkin LymphomaNCT04774068Walter Hanel5
已完成
2 期
Romidepsin and Lenalidomide in Treating Patients With Previously Untreated Peripheral T-Cell LymphomaAdult Nasal Type Extranodal NK/T-cell LymphomaAngioimmunoblastic T-cell LymphomaHepatosplenic T-cell LymphomaPeripheral T-cell LymphomaStage I Cutaneous T-cell Non-Hodgkin LymphomaStage IA Mycosis Fungoides/Sezary SyndromeStage IB Mycosis Fungoides/Sezary SyndromeStage II Cutaneous T-cell Non-Hodgkin LymphomaStage IIA Mycosis Fungoides/Sezary SyndromeStage IIB Mycosis Fungoides/Sezary SyndromeStage III Cutaneous T-cell Non-Hodgkin LymphomaStage IIIA Mycosis Fungoides/Sezary SyndromeStage IIIB Mycosis Fungoides/Sezary SyndromeStage IV Cutaneous T-cell Non-Hodgkin LymphomaStage IVA Mycosis Fungoides/Sezary SyndromeStage IVB Mycosis Fungoides/Sezary SyndromeAnaplastic Large Cell LymphomaNCT02232516Northwestern University30
已完成
2 期
Romidepsin Plus 3BNC117 Phase 2a StudyHuman Immunodeficiency Virus (HIV)NCT02850016Rockefeller University48