A Phase 1b/2 Study of Repeat rAdiation, Minocycline, and Bevacizumab in Patients With Recurrent gliOma (RAMBO)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
The primary objective of step 1 is the rate of adverse events of minocycline and bevacizumab during reirradiation and of step 2 is the response rate to bevacizumab, reirradiation, and minocycline. The secondary objectives are the response rate, Progression Free Survival (PFS)-3, PFS-6, and effects on quality of life and cognition from repeat radiation and bevacizumab.
详细描述
After providing informed consent, patients will undergo screening for eligibility to participate in the study. Screening will start within 21 days prior to dosing.
Subjects will have an MRI within 21 days of starting radiation. QOL and cognition measures will be performed within 21 days of starting radiation. Radiation will be given with parameters determined on an individual basis by the radiation oncologist. Bevacizumab will be continued at 10mg/kg IV every 2 weeks. Minocycline will be given twice a day starting at 100mg PO bid. MRI, QOL, and cognitive tests will be obtained 1, 3 and 6 months after the end of radiation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Male or female patients ≥18 years old with a life expectancy of at least 8 weeks
- •Radiographically proven recurrent (≥ first relapse), intracranial glioma
- •Previous treatment with external beam radiation
- •Radiographic progression on current or prior bevacizumab treatment
- •Women of child-bearing potential must have a negative pregnancy test within 7 days of initiation of dosing and must agree to use an acceptable method of birth control while on study drug and for 3 months after the last dose. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year. Men of child-bearing potential must also agree to use an acceptable method of birth control while on study drug, and for 3 months after the last dose.
- •Karnofsky performance status of ≥50
- •Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.0 x 109/L, Hgb >9 g/dL, platelet count ≥50 x 109/L, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5x ULN, creatinine ≤1.5x ULN)
- •Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements
- •Systolic blood pressure ≤ 160 mg Hg or diastolic pressure ≤ 90 mg Hg within 14 days prior to study registration
- •Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on warfarin confirmed by testing within 14 days prior to study registration
- •Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight (LMW) heparin) must have no active bleeding or pathological condition that carries a high risk of bleeding, and must be on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
排除标准
- •Use of an investigational drug within 14 days or within 5 half-lives of teh investigational drug, whichever is shorter
- •Progression within 3 months of previous radiation by Radiographic Assessment in Neurooncology (RANO) criteria
- •History of Grade 2 (CTCAE v4) or greater acute intracranial hemorrhage
- •A concurrent active cancer that requires non-surgical therapy (e.g. chemotherapy, radiation, adjuvant therapy).
- •Patients with serious illnesses, uncontrolled infection, medical conditions, or other medical history including abnormal laboratory results, which in the investigator's opinion would be likely to interfere with a patient's participation in the study, or with the interpretation of the results
- •Women of child-bearing potential who are pregnant or breast feeding
- •Unstable angina and/or congestive heart failure in the last 6 months, transmural myocardial infarction within the last 6 months, New York Heart Association grade II or higher congestive heart failure requiring hospitalization within 12 months prior to registration, evidence of recent myocardial infarction by EKG performed within 14 days of registration, serious or inadequately controlled cardiac arrhythmia, significant vascular and peripheral vascular disease, evidence of bleeding diathesis or coagulopathy
- •History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months
- •Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for tumor resection
- •Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
- •Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity
研究组 & 干预措施
Dose Level 0: 100 mg bid
Patients receiving minocycline 100 mg bid, bevacizumab, and radiation therapy.
干预措施: Bevacizumab (Drug)
Dose Level 0: 100 mg bid
Patients receiving minocycline 100 mg bid, bevacizumab, and radiation therapy.
干预措施: Minocycline (Drug)
Dose Level 0: 100 mg bid
Patients receiving minocycline 100 mg bid, bevacizumab, and radiation therapy.
干预措施: Radiation (Radiation)
Dose Level 1: 200 mg bid
Patients receiving minocycline 200 mg bid, bevacizumab, and radiation therapy.
干预措施: Bevacizumab (Drug)
Dose Level 1: 200 mg bid
Patients receiving minocycline 200 mg bid, bevacizumab, and radiation therapy.
干预措施: Minocycline (Drug)
Dose Level 1: 200 mg bid
Patients receiving minocycline 200 mg bid, bevacizumab, and radiation therapy.
干预措施: Radiation (Radiation)
Dose Level 2: 400 mg bid
Patients receiving minocycline 400 mg bid, bevacizumab, and radiation therapy.
干预措施: Bevacizumab (Drug)
Dose Level 2: 400 mg bid
Patients receiving minocycline 400 mg bid, bevacizumab, and radiation therapy.
干预措施: Minocycline (Drug)
Dose Level 2: 400 mg bid
Patients receiving minocycline 400 mg bid, bevacizumab, and radiation therapy.
干预措施: Radiation (Radiation)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: From first dose of study treatment to 28 days following radiation therapy (7-8 weeks)
Adverse Events were assessed from start of minocycline treatment (one day prior to start of radiation therapy) until 28 days following the end of radiation therapy. Adverse events were assessed using the Common Terminology for Adverse Events (CTCAE) version 4.0. Each event was assigned a grade (1-5), with lower grades indicating milder events. Events were categorized as severe (grade 3-4) or non-severe (grade 1-2). All adverse events were recorded, regardless of attribution to study treatment. Reported below are the number of patients who experienced any non-severe AE and the number of patients who experienced any severe AE. A full listing of AEs (severe and non-severe) are listed in the Adverse Events module of the Results section.
次要结局
- Progression Free Survival (PFS) at 3 Months(From start of study treatment until 12 weeks after radiation therapy (15-16 weeks))
- Progression Free Survival (PFS) at 6 Months(From start of study treatment until 26 weeks after radiation therapy (29-30 weeks))
- Tabulation of Tumor Best Responses(From start of study treatment until 26 weeks after radiation therapy (29-30 weeks))
- Quality of Life Change Over Time(From start of study treatment until 26 weeks after radiation therapy (29-30 weeks))
- Cognitive Change Over Time - DET(From start of study treatment until 26 weeks after radiation therapy (29-30 weeks))
- Cognitive Change Over Time - IDN(From start of study treatment until 26 weeks after radiation therapy (29-30 weeks))
- Cognitive Change Over Time - OCLT(From start of study treatment until 26 weeks after radiation therapy (29-30 weeks))
- Cognitive Change Over Time - GMLT(From start of study treatment until 26 weeks after radiation therapy (29-30 weeks))