NCT01994590终止2 期
A Phase II Study of Dovitinib (TKI258) Combined With Abiraterone Acetate in Patients With Metastatic Castrate-Resistant Prostate Cancer Evaluating Markers of FGF and AR Signaling in Bone Marrow and Plasma
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
- 4
- 试验地点
- 1
- 主要终点
- Safety and Tolerability
研究概览
简要总结
The goal of this clinical research study is to learn if adding dovitinib to the combination of abiraterone acetate and prednisone may help to control metastatic CRPC. The safety of this drug combination will also be studied.
详细描述
Study Drug Administration:
If you are found to be eligible to take part in this study, you will take the study drugs in 28-day cycles.
Dovitinib:
You will take dovitinib capsules by mouth 1 time each day on Days 1-5, 8-12, 15-19, and 22-26 of each cycle. You should take the dovitinib with about a cup (8 ounces) of water. You may take dovitinib with or without food.
If you miss a dose of dovitinib on Days 1-4, 8-11, 15-18, or 22-25, you should not make up the dose on the same day. You should continue taking the drug as scheduled the following day.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Patient or his legally authorized representative must provide written informed consent.
- •Age >/= 18
- •Eastern Cooperative Oncology Group (ECOG) performance status </= 2
- •Histologic evidence of prostate adenocarcinoma
- •Diagnosis of metastatic castration-resistant prostate cancer, with measureable disease (lymph nodes and/or visceral metastases by RECIST) or bone metastases.
- •Patients must have surgical or ongoing chemical castration (with LHRH agonists or LHRH antagonists), with a baseline testosterone level < 50ng/dL
- •Patients must have documented evidence of progressive disease as defined by any of the following: a) PSA progression: minimum of 2 rising values (3 measurements) obtained a minimum of 7 days apart with the last result being at least >/= 2.0 ng/mL; b) New or increasing non-bone disease (RECIST); c) A positive bone scan with 2 or more new lesions (PCWG2). Patients must have evidence for metastatic prostate cancer by bone scan and/or CT/MRI (i.e., soft tissue, visceral, lymph node). If lymph node, visceral and/or soft-tissue metastases are the only evidence of metastasis, at least one lesion must be >/= 1.5 cm in diameter.
- •Laboratory requirements: a) Absolute neutrophil count (ANC) >/= 1,500/ml; b) Platelets >/= 100,000/ml; c) Total bilirubin </= 1.5 x upper limit of normal (ULN); d) Serum glutamate pyruvate transaminase (SGPT) (ALT) AND/OR Serum glutamate oxaloacetate transaminase (SGOT) (AST) </= 3.0 x ULN; e) Creatinine </= 1.5 x ULN; f) White blood cell count (WBC) >/= 3,000 uL; g) Hb >/= 8.0 g/dL independent of transfusion
- •Men whose partner is a woman of childbearing potential must be willing to consent to using effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) while on treatment and for at least 3 months thereafter.
- •Patients may have received prior treatment with androgen ablative therapies (e.g. bicalutamide, DES, enzalutamide) and/or "targeted" therapies (such as tyrosine kinase inhibitors). Androgen ablative therapies must be discontinued >/=3 days prior to initiation of study treatment with the exception of enzalutamide which may be continued during protocol treatment per the practice preference of the treating physician. Patients who are predicted to benefit from an antiandrogen withdrawal response should be tested for this possibility before being considered for eligibility to this study. Targeted therapies must be discontinued >/= 2 weeks before initiation of study treatment.
- •Patients may have received up to 2 prior cytotoxic chemotherapy regimens for the treatment of metastatic castration-resistant disease, but these therapies must be discontinued >/= 3weeks before initiation of study treatment. At least one of the regimens must have contained docetaxel and patients must have recovered to < Grade 2 adverse events from prior chemotherapy or to pretreatment baseline
排除标准
- •Patients with histologic evidence of small cell carcinoma of the prostate
- •Prior therapy with dovitinib or abiraterone acetate or other FGF targeted therapy
- •Radiation therapy (including palliative radiotherapy to a metastatic lesion) within 14 days
- •Major surgery (e.g., open abdominal, pelvic, thoracic, orthopedic or neurosurgery) within 28 days of the date of the first dose of study drugs
- •Samarium-153 within 28 days of the date of the first dose of study drugs, or Strontium-89 within 12 weeks (84 days) of the date of the first dose of study drugs. Patients who have received 2 or more doses of bone-seeking radioisotopes are not eligible
- •Current treatment on another therapeutic clinical trial
- •Impending complication from bone metastases (fracture and/or cord compression). Properly treated or stabilized fractures and/or cord compression is allowed
- •Presence of ongoing urinary obstruction (e.g., urinary retention, hydronephrosis) requiring medical intervention. Urinary obstruction relieved with treatment is allowed
- •Patient has an uncontrolled intercurrent illness (e.g., uncontrolled diabetes, uncontrolled hypertension)
- •Patient has another serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the patient's ability to provide informed consent or with the completion of treatment according to this protocol
- •Patients with an active second malignancy that could, in the investigator's opinion, potentially interfere with the patient's ability to participate and/or complete this trial
- •Patients with known brain metastases
- •Impaired cardiac function or clinically significant cardiac diseases, including any of the following: a.) History or presence of serious uncontrolled ventricular arrhythmias; b. Clinically significant resting bradycardia; c.) Left ventricular ejection fraction (LVEF) assessed by 2-D echocardiogram (ECHO) < 50% or lower limit of normal (whichever is the higher), or 2-D multiple gated acquisition scan (MUGA) < 45% or lower limit of normal (whichever is the higher); d.) Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA);
- •(Exclusion #14 continued) e.) Chronically uncontrolled hypertension, defined conventionally as consistent/repeated systolic pressures above 140 mmHg or diastolic pressures above 90 mmHg despite anti-hypertensive therapy. This may be established with home BP readings. There is no criterion related to a specific BP result required for eligibility, nor are acute BP elevations that are related to iatrogenic causes, acute pain, or other transient reversible causes considered an exclusion criterion. The intent is to exclude patients with chronically uncontrolled hypertension that might be further exacerbated by the study drugs.
- •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or gastric or small bowel resection)
- •Cirrhosis, chronic active hepatitis or chronic persistent hepatitis
- •Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) or hepatitis B virus (HBV) or hepatitis C virus (HCV) disease or antigen positivity
- •Initiation of bisphosphonate and/or RANKL inhibitors within 4 weeks prior to first dose of study drug. Patients already on stable doses of bisphosphonates and/or RANKL inhibitors may continue these drugs. However, patients are not allowed to initiate bisphosphonate and/or RANKL inhibitors during the study
- •Any bleeding dyscrasia
研究组 & 干预措施
Dovitinib + Abiraterone Acetate + Prednisone
Experimental
Participants receive a single daily oral dose of Dovitinib for 5 consecutive days, on Days 1-5, 8-12, 15-19, and 22-26 of each 28 day cycle. Starting dose will be 400 mg daily.
Participant to take 4 tablets (250 mg each) orally (PO) daily of Abiraterone acetate.
Participant to take 5 mg oral prednisone, twice daily.
干预措施: Dovitinib (Drug)
Dovitinib + Abiraterone Acetate + Prednisone
Experimental
Participants receive a single daily oral dose of Dovitinib for 5 consecutive days, on Days 1-5, 8-12, 15-19, and 22-26 of each 28 day cycle. Starting dose will be 400 mg daily.
Participant to take 4 tablets (250 mg each) orally (PO) daily of Abiraterone acetate.
Participant to take 5 mg oral prednisone, twice daily.
干预措施: Abiraterone Acetate (Drug)
Dovitinib + Abiraterone Acetate + Prednisone
Experimental
Participants receive a single daily oral dose of Dovitinib for 5 consecutive days, on Days 1-5, 8-12, 15-19, and 22-26 of each 28 day cycle. Starting dose will be 400 mg daily.
Participant to take 4 tablets (250 mg each) orally (PO) daily of Abiraterone acetate.
Participant to take 5 mg oral prednisone, twice daily.
干预措施: Prednisone (Drug)
结局指标
主要结局
Safety and Tolerability
时间窗: Participants are followed while actively taking study drug and for at least 30 days post last dose.
Number of Participants with Adverse Events
次要结局
未报告次要终点
研究者
研究点 (1)
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