NCT01120275终止2 期
Phase II Study of RO4929097 (NSC-749225) in Advanced Melanoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 36
- 试验地点
- 178
- 主要终点
- Overall Survival
研究概览
简要总结
This phase II trial is studying how well gamma-secretase/Notch signalling pathway inhibitor RO4929097 works in treating patients with stage IV melanoma. Gamma-secretase/Notch signalling pathway inhibitor RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To assess the six-month progression-free survival and one-year overall survival probability in Stage IV melanoma patients treated with RO4929097 (gamma-secretase/Notch signalling pathway inhibitor RO4929097).
SECONDARY OBJECTIVES:
I. To investigate in a preliminary manner the relationship between Notch activation status and gene expression profile of tumor and clinical outcomes from patients in this study.
II. To study the effects of the investigational therapy on T cell function, which will provide a basis for subsequent trials combining Notch blockade with immunomodulatory therapy for advanced melanoma.
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 confirmed melanoma of cutaneous or unknown origin (ocular primary and mucosal primary excluded); patients must have Stage IV disease
- •All patients must undergo a computed tomography (CT) or magnetic resonance imaging (MRI) of the brain within 42 days prior to registration that is negative for brain metastases; patients with a history of brain metastases are ineligible
- •Patients must have measurable disease; all measurable lesions must be assessed (by physical examination, CT, or MRI scan) within 28 days prior to registration; tests to assess non-measurable disease must be performed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria In Solid Tumors [RECIST] 1.1); the CT from a combined positron emission tomography (PET)/CT must not be used to document measurable disease unless it is of diagnostic quality
- •Sites must offer all patients participation in translational medicine studies and banking of paraffin embedded tissue and whole blood
- •Patients must not have received any prior systemic therapy for Stage IV disease except for noncytotoxic biologic agents (e.g., vaccines, cytokines, cell therapies that do not require cytotoxic agents); patients may have received prior treatment with up to two prior biological therapies - no cytotoxics or kinase inhibitors - for advanced disease
- •Patients may have had prior adjuvant immunotherapy with biological response modifiers (examples include but are not limited to interferon, vaccines, GM-CSF, and CTLA-4 blocking antibodies); prior adjuvant immunotherapy must have been completed at least 28 days prior to registration
- •Adjuvant therapy containing cytotoxic agents is allowed if completed >= 180 days prior to registration
- •Patients may have received prior radiation therapy; any side effects the patients had due to prior radiation therapy must have resolved to =< Grade 1 prior to registration; prior radiation therapy must have completed at least 28 days prior to registration
- •Patients must have Zubrod performance status of 0-1
- •Leukocytes >= 3,000/mcL
- •Absolute neutrophil count (ANC) >= 1,500/mcL
- •Platelets >= 100,000/mcL
- •Hemoglobin >= 9 g/dL
- •Total bilirubin =< institutional upper limit of normal (IULN)
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x IULN
- •Serum creatinine =< IULN OR measured or calculated creatinine clearance >= 60 mL/min
- •Patients must have the following serum electrolytes within the institutional ranges of normal: potassium, sodium, magnesium, phosphorous, chloride and calcium (corrected for serum albumin); these tests must be performed within 28 days prior to registration; patient must not require parenteral replacement therapy
- •Patients must not have a history of allergic reaction attributed to compounds of similar chemical or biologic composition to RO4929097
- •Patients must be able to swallow tablets
- •Patients must not have malabsorption syndrome or other condition that would interfere with intestinal absorption of the agent
- •Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin), are ineligible
- •Patients must not be taking strong inducers or strong inhibitors of CYP3A4 at the time of registration
- •Patients must not be known to be serologically positive for Hepatitis A, B, or C, or have a history of liver disease, other forms of hepatitis, or cirrhosis
- •Patients must have an ECG within 28 days prior to registration. Patients must not have a QTcF > 450 msec (males) or QTcF > 470 msec (females)
- •Patients must not have symptomatic congestive heart failure or unstable angina pectoris
- •Patients with a history of torsades de pointes or any significant cardiac arrhythmia (except asymptomatic unifocal ventricular premature beats or supraventricular tachycardia easily controlled with oral medications) are excluded; any patient requiring or expected to require antiarrhythmics or other therapy known to prolong QTc is also excluded
- •No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
- •Women of childbearing potential must have a negative pregnancy test within 14 days prior to registration (the type of pregnancy test used is at the discretion of the registering institution); female patients of childbearing potential include the following:
- •Patients with regular menses
- •Patients, after menarche with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding
- •Women who have had tubal ligation
- •Women must not be nursing due to possible harm to a nursing infant from the treatment regimen
- •All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
- •At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base
排除标准
- 未提供
研究组 & 干预措施
Treatment (gamma-secretase inhibitor RO4929097)
Experimental
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: gamma-secretase/Notch signalling pathway inhibitor RO4929097 (Drug)
Treatment (gamma-secretase inhibitor RO4929097)
Experimental
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Overall Survival
时间窗: Weekly, up to 3 years.
From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Progression-free Survival According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
时间窗: Disease assessments were performed every 6 weeks, up to 3 years.
From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause.
次要结局
- Percentage of Participants With Confirmed and Unconfirmed Complete or Partial Response(Disease assessments for response were performed every 6 weeks, up to 3 years)
- Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs(Toxicity assessment was evaluated at least every 3 weeks at the beginning of each cycle, up to 3 years)
研究者
研究点 (178)
Loading locations...
相似试验
终止
2 期
Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Recurrent or Progressive GlioblastomaAdult Giant Cell GlioblastomaAdult GlioblastomaAdult GliosarcomaRecurrent Adult Brain TumorNCT01122901National Cancer Institute (NCI)47
已完成
2 期
Gamma Secretase Inhibitor RO4929097 in Previously Treated Metastatic Pancreas CancerAdenocarcinoma of the PancreasRecurrent Pancreatic CancerStage IV Pancreatic CancerNCT01232829National Cancer Institute (NCI)18
撤回
2 期
RO4929097 After Autologous Stem Cell Transplant in Treating Patients With Multiple MyelomaDS Stage I Plasma Cell MyelomaDS Stage II Plasma Cell MyelomaDS Stage III Plasma Cell MyelomaRefractory Plasma Cell MyelomaNCT01251172National Cancer Institute (NCI)
终止
2 期
Gamma-secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced, Metastatic, or Recurrent Triple Negative Invasive Breast CancerEstrogen Receptor-negative Breast CancerHER2-negative Breast CancerProgesterone Receptor-negative Breast CancerRecurrent Breast CancerStage IIIA Breast CancerStage IIIB Breast CancerStage IIIC Breast CancerStage IV Breast CancerMale Breast CancerTriple-negative Breast CancerNCT01151449National Cancer Institute (NCI)6
已完成
1 期
RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant GliomaAdult Anaplastic (Malignant) MeningiomaAdult Anaplastic AstrocytomaAdult Anaplastic EpendymomaAdult Brain Stem GliomaAdult Choroid Plexus NeoplasmAdult CraniopharyngiomaAdult Diffuse AstrocytomaAdult EpendymoblastomaAdult EpendymomaAdult Giant Cell GlioblastomaAdult GlioblastomaAdult GliosarcomaAdult Grade I MeningiomaAdult Grade II MeningiomaAdult MedulloblastomaAdult Mixed GliomaAdult Myxopapillary EpendymomaAdult OligodendrogliomaAdult Papillary MeningiomaAdult Pilocytic AstrocytomaAdult Pineal Gland AstrocytomaAdult PineoblastomaAdult PineocytomaAdult Primary Melanocytic Lesion of MeningesAdult Subependymal Giant Cell AstrocytomaAdult SubependymomaAdult Supratentorial Primitive Neuroectodermal TumorMalignant Adult Intracranial HemangiopericytomaAcoustic SchwannomaNCT01119599National Cancer Institute (NCI)22