Concurrent Angiogenic and EGFR Blockade in Conjunction With Curative Intent Chemoradiation for Locally Advanced Head and Neck Cancer
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Tumor Resolution
研究概览
简要总结
Radiotherapy (RT) with concurrent chemotherapy represents the state of the art in curative intent treatment for locally advanced squamous carcinoma of the head and neck. Tumor hypoxia and high levels of angiogenesis (blood vessel formation) are associated with treatment failure. Preclinical models reveal that radiotherapy itself may induce tumor secretion of vascular endothelial growth factor (VEGF). Curability may consequently be reduced by multiple mechanisms. Over-expression of epidermal growth factor receptor (EGFR) also occurs commonly and increases the risk of treatment failure. The addition of EGFR blockade to RT alone increases the chance of a cure. Concurrent VEGF and EGFR blockade could be synergistic with one another and improve the effectiveness of concurrent chemoradiation for advanced head and neck cancer.
This study will add angiogenic and epidermal growth factor receptor (EGFR) blockade into an established program of curative intent concurrent chemoradiation for locally advanced head and neck cancer. The safety and effectiveness of delivering the drugs bevacizumab and Tarceva in conjunction with twice daily irradiation and concurrent cisplatin (CDDP) chemotherapy will be determined.
详细描述
Pre Radiation Period:
- Bevacizumab (10 mg/kg) on days -14 and 0, or
- Tarceva (100 mg) daily from -14-0, or
- Bevacizumab (10 mg/kg) on days -14 and 0; Tarceva (100 mg) daily from -14-0
Chemoradiation Period:
-
Radiotherapy may be delivered via conventional 2-D, conformal 3-D, or intensity modulated (IMRT) technique as is clinically indicated. Radiotherapy and CDDP doses will be delivered uniformly to all treatment cohorts:
-
RT: 1.25 Gy BID M-F with a 6 hour interfraction interval
-
Treatment break during week 4. Total dose 70 Gy/7 weeks
-
CDDP: 33 mg/m2 M-W on weeks 1 and 5 of RT with standard DUMC hydration and anti-emetic regimens
-
Bevacizumab (10mg/kg): Monday of weeks 1, 3, 5, 7 of RT
-
Tarceva (100 mg): Daily for weeks 1-7 of treatment, except for days receiving CDDP
研究设计
- 研究类型
- Interventional
- 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
- •Locally advanced squamous carcinoma of the head and neck (AJCC stages II/IV, M0, and excluding T1N1 and T1N2) undergoing curative intent concurrent chemoradiation.
- •Previous treatment of any sort other than a biopsy is not allowed.
- •Eligible anatomic sites:
- •oral cavity
- •oropharynx
- •hypopharynx
- •supraglottic
- •glottic larynx
- •KPS > 60
排除标准
- •Nasopharynx primary
- •History of malignancy other than basal cell skin cancer.
- •History of claudication, bleeding, or thromboembolic disorders. Patients receiving heparin or Coumadin therapy are ineligible.
- •Primary tumor or lymph node encasement of the carotid artery
- •Blood pressure of >150/100 mmHg
- •Unstable angina
- •New York Heart Association (NYHA) Grade II or greater congestive heart failure
- •History of myocardial infarction within 6 months
- •History of stroke within 6 months
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0; anticipation of need for major surgical procedure during the course of the study.
- •Minor surgical procedures, fine needle aspirations, or core biopsies within 7 days prior to Day 0
- •Pregnant (positive pregnancy test) or lactating
- •Urine protein : creatinine ratio ≥ 1.0 at screening
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
- •Serious, non-healing wound, ulcer, or bone fracture
- •AST, ALT, or bilirubin > 1.5 x normal
- •PT or PTT > 1.5 x normal
- •Platelets < 100,000
- •WBC < 2000
- •Hgb < 10
- •Creatinine clearance < 60 mL/hr
- •Refusal to provide written informed consent
研究组 & 干预措施
ChemoRadiotherapy
Radiation Therapy concurrent with cisplatin chemotherapy, Avastin and Tarceva
干预措施: Chemoradiotherapy (Radiation)
ChemoRadiotherapy
Radiation Therapy concurrent with cisplatin chemotherapy, Avastin and Tarceva
干预措施: Cisplatin (Drug)
ChemoRadiotherapy
Radiation Therapy concurrent with cisplatin chemotherapy, Avastin and Tarceva
干预措施: Bevacizumab (Drug)
ChemoRadiotherapy
Radiation Therapy concurrent with cisplatin chemotherapy, Avastin and Tarceva
干预措施: Erlotinib (Drug)
结局指标
主要结局
Tumor Resolution
时间窗: Within 30 days of completing RT
Complete response (resolution) of tumor on clinical exam.
次要结局
- Failure Free Survival(3 yrs)
- Local Regional Control(1 yr following chemoradiation)
研究者
David M. Brizel, MD
Professor, Radiation Oncology
Duke University