Randomized Phase II Study Comparing the MET Inhibitor Cabozantinib to Temozolomide/Dacarbazine in Ocular Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 228
- 主要终点
- Proportion of Patients Without a Progression Free Survival Event at 4 Months (PFS4)
研究概览
简要总结
This randomized phase II trial studies how well cabozantinib-s-malate works compared with temozolomide or dacarbazine in treating patients with melanoma of the eye (ocular melanoma) that has spread to other parts of the body and cannot be removed by surgery. Cabozantinib-s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide and dacarbazine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether cabozantinib-s-malate works better than temozolomide or dacarbazine in treating patients with melanoma of the eye.
详细描述
PRIMARY OBJECTIVES:
I. Compare the progression-free survival rate at 4 months (PFS4) of patients with ocular melanoma treated with cabozantinib-s-malate (cabozantinib) or temozolomide (or dacarbazine).
SECONDARY OBJECTIVES:
I. Estimate the distribution of progression-free survival (PFS) times. II. Estimate the distribution of overall survival (OS) times. III. Estimate the confirmed response rate as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
IV. Assess the safety of these agents by examining the toxicity profile. V. Correlate the response of MET molecular status.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Histologically or cytologically confirmed uveal melanoma that is metastatic or unresectable; if histologic or cytologic confirmation of the primary is not available, confirmation of the primary diagnosis of uveal melanoma by the treating investigator can be clinically obtained, as per standard practice for uveal melanoma; pathologic confirmation of diagnosis will be performed at the participating site
- •Measurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan or magnetic resonance imaging (MRI)
- •Prior systemic therapies allowed, except for those treatments directed toward, or with activity against, c-Met or vascular endothelial growth factor/receptor (VEGF/R), and the chemotherapy agents temozolomide and dacarbazine; prior treatment must have been no earlier than 3 weeks prior to starting treatment with cabozantinib with exceptions noted below and the following: at least 4 weeks since prior hepatic infusion or at least 2 weeks since radiation therapy
- •No cytotoxic chemotherapy including investigational cytotoxic chemotherapy or biologic agents (e.g., cytokines or antibodies) within the last 3 weeks, or nitrosoureas/mitomycin C within 6 weeks before the first dose of study treatment; at least 6 weeks must have elapsed if the last regimen included an anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) antibody; patients must have experienced disease progression on their prior therapy in the opinion of the treating investigator
- •No prior radiation therapy within the last 4 weeks, except as below
- •To the thoracic cavity, abdomen, or pelvis within 12 weeks before the first dose of study treatment, or has ongoing complications, or is without complete recovery to < grade 1 toxicity
- •To bone or brain metastasis within 14 days before the first dose of study treatment
- •To any other site(s) within 28 days before the first dose of study treatment
- •Prior radiation treatment may have included no more than 3000 centigray (cGy) to fields including substantial bone marrow
- •No prior radionuclide treatment within 6 weeks of the first dose of study treatment
- •No prior treatment with a small molecule kinase inhibitor or a hormonal therapy within 14 days or 5 half-lives (whichever is longer)
- •No concomitant anti-cancer therapy unless specified above
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
- •A corrected QT interval calculated by the Fridericia formula (QTcF) =< 500 ms within 28 days before randomization; Note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the patient meets eligibility in this regard
- •Common Terminology Criteria for Adverse Events (CTCAE) recovered to baseline or CTCAE =< grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant adverse events (AEs)
- •No active brain metastases or epidural disease; patients with brain metastases previously treated with whole brain radiation or radiosurgery or patients with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible; neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 12 weeks before starting study treatment; baseline brain imaging with contrast-enhanced CT or MRI scans for patients with known brain metastases is required to confirm eligibility
- •No clinically significant gastrointestinal bleeding within 24 weeks before the first dose of study treatment
- •No hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 12 weeks before the first dose of study treatment
- •No signs indicative of pulmonary hemorrhage within 12 weeks before the first dose of study treatment
- •No prior radiographic evidence of cavitating pulmonary lesion(s)
- •No tumor in contact with, invading or encasing any major blood vessels
- •No evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of treatment
- •The patient may not have uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
- •Cardiovascular disorders including:
- •Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening
- •Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mmHg systolic, or > 90 mmHg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
- •Any history of congenital long QT syndrome
- •Any of the following within 24 weeks before the first dose of study treatment:
- •Unstable angina pectoris
- •Clinically-significant cardiac arrhythmias
- •Stroke (including transient ischemic attack [TIA], or other ischemic event)
- •Myocardial infarction
- •Thromboembolic event requiring therapeutic anticoagulation (Note: patients with a venous filter [e.g. vena cava filter] are not eligible for this study)
- •Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
- •Any of the following within 28 days before the first dose of study treatment
- •Intra-abdominal tumor/metastases invading GI mucosa
- •Active peptic ulcer disease
- •Inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis
- •Malabsorption syndrome
- •Any of the following within 24 weeks before the first dose of study treatment:
- •Abdominal fistula
- •Gastrointestinal perforation
- •Intra-abdominal abscess; Note: complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more that 24 weeks before the first dose of study treatment
- •Bowel obstruction or gastric outlet obstruction
- •Other clinically significant disorders such as:
- •Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
- •History of organ transplant
- •Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment
- •History of major surgery as follows:
- •Major surgery in past 8 weeks of the first dose of cabozantinib if there were no wound healing complications or within 24 weeks of the first dose of cabozantinib if there were wound complications
- 另有 37 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm I (cabozantinib-s-malate)
Patients receive cabozantinib-s-malate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Cabozantinib S-malate (Drug)
Arm I (cabozantinib-s-malate)
Patients receive cabozantinib-s-malate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (temozolomide or dacarbazine)
Patients receive temozolomide PO daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. If temozolomide is not available, patients receive dacarbazine IV over 15-60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Dacarbazine (Drug)
Arm II (temozolomide or dacarbazine)
Patients receive temozolomide PO daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. If temozolomide is not available, patients receive dacarbazine IV over 15-60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (temozolomide or dacarbazine)
Patients receive temozolomide PO daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. If temozolomide is not available, patients receive dacarbazine IV over 15-60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Temozolomide (Drug)
结局指标
主要结局
Proportion of Patients Without a Progression Free Survival Event at 4 Months (PFS4)
时间窗: At 4 months
A patient will be declared a PFS4 success if they are on study and progression free for at least 4 months. Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, with an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. The success for each arm will be calculated independently as the number of successes divided by the total number of evaluable patients. A one-sided chi-squared test for a difference in PFS4 proportions will be used to test for a difference between arms.
次要结局
- Percentage of Patients Who Experienced Grade 3+ Adverse Events Regardless of Attribution(Up to 2 years)
- Overall Survival (OS)(Number of days from registration until death, assessed up to 2 years)
- PFS(Number of days from registration until disease progression (or death), assessed up to 2 years)
- Confirmed Response Rate as Determined by the RECIST Criteria (Version 1.1)(Up to 2 years)