NCT02880943Unknown1 期
Phase I/II Dose-finding, Safety and Efficacy Study of Radium-223 Dichloride (XOFIGO®) in Renal Cell Carcinoma Patients With Bone Metastases.
Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie5 个研究点 分布在 1 个国家目标入组 42 人开始时间: 2016年10月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 42
- 试验地点
- 5
- 主要终点
- Dose-limiting toxicities (DLT)
研究概览
简要总结
This is a prospective, multicentre, open-label, phase I/II study to evaluate the maximum tolerated dose (MTD), and the most successful dose (MSD) of XOFIGO®, in renal cancer patients with metastases to bone, without (Group A) or with (Group B) visceral metastases.
详细描述
This is a prospective, multicentre, open-label, phase I/II study to evaluate the maximum tolerated dose (MTD), and the most successful dose (MSD) of XOFIGO®, in renal cancer patients with metastases to bone, without (Group A) or with (Group B) visceral metastases.
Dose-finding will be performed according to the Continual Reassessment Method (CRM) using either toxicity (escalation cohort) or joined toxicity-efficacy (expansion cohort) endpoints.
Two groups of patients will be evaluated:
- Group A: patients with bone disease mainly will be treated with XOFIGO® alone. (node and/or adrenal metastases and/or ≤5 lung metastases ≤1cm each are allowed in Group A).
- Group B: patients already treated with an ongoing approved Tyrosine Kinase Inhibitor (TKI) for their visceral metastases will be treated with XOFIGO® for bone disease.
XOFIGO® will be administered intravenously as a bolus injection every 4 weeks with a maximum of 6 administrations per patient. Four dose levels are available for evaluation : 27.5 kBq/kg, 55 kBq/kg, 88 kBq/kg and 110 kBq/kg.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 confirmed metastatic renal cell carcinoma with a clear cell component.
- •Bone metastases upon bone scan with no CT and MRI performed any time within period of 4 weeks prior to study entry, with at least one evaluable unidimensional bone lesion (i.e., ≥1 malignant tumour mass that can be accurately measured in at least 1 dimension ≥ 10 mm on T1-weighted Magnetic Resonance Imaging [MRI]).
- •Group A: bone metastases (lymph nodes and/or adrenal metastases, and/or ≤ 5 lung metastases of less than 1 cm each, are allowed).
- •Group B: bone metastases AND visceral metastases upon MRI (according to revised RECIST 1.1 criteria).
- •Patient in a) first (naïve), or b) second or third line setting receiving or about to receive an approved Tyrosine Kinase Inhibitor (patients on mTOR inhibitors are not eligible).
- •Male or female, age ≥18 years at ICF signature time.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Good or Intermediate prognostic group according to the International Metastatic Database Consortium (IMDC).
- •At least 4 weeks from the end of a previous systemic treatment, if any, with resolution of all treatment-related toxicity according to NCI CTCAE Version 4.03 grade ≤ 1 except for alopecia.
- •Palliative local treatment allowed if performed ≥ 2 weeks prior to study entry for radiotherapy, cementoplasty or minor surgery; ≥ 4 weeks prior to study entry for major surgery.
- •Adequate organ function defined by the following criteria:
- •Absolute Neutrophils count (ANC) ≥1 500 cells/mm3
- •Platelets ≥100 000 cells/mm3
- •Haemoglobin ≥ 9.0 g/dL
- •AST and ALT ≤ 2.5 x upper limit of normal (ULN), unless there are liver metastases in which case AST and ALT ≤5.0 x ULN
- •Total bilirubin ≤ 1.5 x ULN
- •Estimated glomerular filtration rate upon MDRD ≥ 50 mL/min
- •Urinary protein < 2+ by urine dipstick. If dipstick is ≥ 2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is < 2 g per 24 hours
- •Corrected calcium ≤ 2.8 mmol/L.
- •Women of childbearing potential must have a negative serum pregnancy test within 7days prior to treatment initiation.
- •Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrolment.
- •Willingness, for men and women,to use effective contraception during study treatment and for 6 months after last dose of study drug.
- •Willingness to comply with protocol requirements.
排除标准
- •Poor prognostic group according to the IMDC.
- •Prior radiotherapy to ≥ 40% of bone marrow, whole pelvic irradiation and/or prior isotope therapy whatever the isotope (any α- or β-emitters).
- •Active secondary cancer including prior malignancy from which the subject has been disease-free for ≤ 3 years (however, adequately treated superficial basal cell skin or cervical carcinoma in situ before 4 weeks prior to entry are eligible to the study).
- •Known brain or leptomeningeal involvement.
- •Any other concurrent serious illness or medical conditions including:
- •Crohn"s disease or ulcerative colitis
- •Bone marrow dysplasia
- •Known presence of osteonecrosis of the jaw
- •Uncontrolled hypertension.
- •Uncontrolled cardiac arrhythmias, angina pectoris, and/or hypertension. History of congestive heart failure, or myocardial infarction within the last 6 months.
- •QTc interval (QTc) assessed by local device > 500ms in the 7 days prior to inclusion.
- •Ongoing biphosphonates, denosumab and/or vitamin D supplementation.
- •Active infection requiring systemic antibiotic or anti-fungal medication.
- •Any contra-indication to MRI, including:
- •Carrying a metallic medical device (e.g. pacemaker) or foreign body prohibiting use of MRI
- •Known allergy to gadolinium or iodine
- •Dysthyroidism precluding usage of iodine contrast agent
- •Pregnant or breast feeding.
- •Participation in another clinical trial with any investigational drug within 30 days prior to study enrolment.
研究组 & 干预措施
Group A
Experimental
Group A: patients with bone disease mainly will be treated with XOFIGO® alone.
Node and/or adrenal metastases and/or ≤5 lung metastases ≤1cm each are allowed in Group A.
干预措施: XOFIGO (Drug)
Group B
Experimental
Group B: patients already treated with an ongoing approved Tyrosine Kinase Inhibitor (TKI) for their visceral metastases will be treated with XOFIGO® for bone disease.
干预措施: XOFIGO (Drug)
结局指标
主要结局
Dose-limiting toxicities (DLT)
时间窗: within 6 weeks after the first injection of XOFIGO
Dose-limiting toxicities (DLT) within the first 6 weeks to determine the MTD. DLT is defined as any XOFIGO related adverse event occurring between C1D1 and C2D15.
次要结局
- Bone clinical benefit rate (bone objective response or stable disease, BCB)(up to 12 months)
- Overall clinical benefit rate (bone and visceral objective response or stable disease, OCB)(up to 12 months)
- Time to bone progression (TTBP) defined as the time from the first administration of XOFIGO® to the bone tumour progression (revised RECIST 1.1 taking into account bone lesions)(up to 12 months)
- Distribution of radium-223 dichloride into the bone assessed with scintigraphy of biodistribution of radium-223 dichloride(Assessed at day 1 after the first Xofigo injection)
- Pain assessment upon Brief Pain Inventory (BPI) and analgesic consumption questionnaire(BPI questionnaire will be completed 7 days before the first administration of XOFIGO® and before each visit.)
- Change From Baseline in the FACT-Kidney Symptom Index-15 (FKSI-15) Scale(7 months (Baseline and at 7 months))
- Bone response concordance between FNa-PET scan and whole-body MRI(up to 12 months)
- Time to occurrence of the first Skeletal-Related Events (SRE)(up to 12 months)
- 1-year overall survival rate (1y-OS) defined as the percentage of patients alive 1 year after 1st administration of XOFIGO®(1 year)
- Change From Baseline in EQ-5D Scale(7 months (Baseline and at 7 months))
- Changes in bone markers(up to 12 months)
- Changes in MRI(up to 12 months)
研究者
研究点 (5)
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