A Phase 3 Randomized Trial of Concurrent Cisplatin & Radiotherapy With Or Without ONCOVEX^GM-CSF In Previously Untreated Patients With Locally Advanced Squamous Cell Carcinoma Of The Head And Neck
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 6
- 主要终点
- 2-year Event-free Survival
研究概览
简要总结
This study is being conducted to learn about the safety and risks of using talimogene laherparepvec to treat patients with head and neck cancer and to see if talimogene laherparepvec and chemoradiation together can destroy the tumours versus the use of chemoradiation alone. This study may provide information on the usefulness of talimogene laherparepvec combined with chemoradiation as a future treatment for head and neck cancer.
详细描述
The objective is to evaluate the efficacy and safety of treatment with chemoradiation (CRT) plus talimogene laherparepvec compared to CRT alone in previously untreated patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) for which surgical resection is not clinical indicated. The efficacy endpoints of the study aim to demonstrate overall clinical benefit for patients treated with talimogene laherparepvec as compared to CRT alone.
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
- •Male or female ≥ 18 years
- •Eastern Co-Operative Oncology Group (ECOG) Performance Status ≤ 1
- •Histological evidence (from the primary lesion and/or lymph nodes) of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx
- •Stage III or IV disease (T2N2-3M0, T3-4N1-3M0)
- •No evidence of distant metastases by computed tomography (CT) or positron emission tomography (PET)/CT scan
- •Life expectancy > 4 months
- •Neutrophil count ≥ 2,000/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Hemoglobin ≥ 10 g/dL
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN
- •Alkaline phosphatase ≤ 2.5 times ULN
- •Creatinine clearance ≥ 60 mL/min
- •Female patients of child-bearing potential (i.e. not surgically sterile, or not having spontaneous amenorrhea for at least 12 months) must agree to use an effective form of contraception during the treatment phase of the study.
- •Male patients must agree to use a condom with spermicide or their female partner must use an effective method of birth control.
- •Provide written informed consent in accordance with all applicable regulations and follow the study procedures. Patients must be capable of understanding the investigational nature, potential risks and benefits of the study.
排除标准
- •Prior treatment for locally advanced SCCHN (No prior surgery for SCCHN except nodal sampling or biopsy for study disease).
- •Patients with T1-2N1 or T1N2-
- •Pre-existing peripheral neuropathy ≥ Grade 2 (motor or sensory).
- •Weight loss > 20% of body weight within 3 months of screening (unless purposeful).
- •Surgery ≤ 28 days before randomization with the exception of feeding tube placement, dental extractions, central venous catheter placement, biopsies and nodal sampling.
- •Cancer of the nasopharynx, sinus, salivary gland or skin.
- •Previous radical radiation therapy (RT) to the head and neck region, excluding superficial RT for a non-melanomatous skin cancer.
- •Prior cancers, except: those diagnosed > 5 years ago with no evidence of disease recurrence and clinical expectation of recurrence of less than 5%; or successfully treated non-melanoma skin cancer; or carcinoma in situ of the cervix.
- •Significant intercurrent illness that will interfere with the chemotherapy or radiation therapy such as human immunodeficiency (HIV) infection, cardiac failure, pulmonary compromise (chronic obstructive pulmonary disease, pneumonia or respiratory decompensation) resulting in hospitalization within 12 months of screening, or active infection.
- •Any significant cardiac disease (e.g., New York Heart Association (NYHA) Class 3 or 4; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty or coronary artery bypass graft (CABG) within the past 6 months; or uncontrolled atrial or ventricular cardiac arrhythmias..
- •High risk for poor compliance with therapy or follow up as assessed by the investigator.
- •Active herpes labialis, other lesions due to herpes simplex virus type I (HSV1) or dermatoses involving or within 50 cm of the lesions to be injected; active HSV1 lesions must have resolved before talimogene laherparepvec is injected.
- •Prior systemic chemotherapy for any type of cancer.
- •Patients for whom radiation therapy is contraindicated.
- •Pregnant or breast-feeding female. Confirmation that women of child-bearing potential are not pregnant. A negative serum β- human chorionic gonadotropin (β-hCG) pregnancy test result must be obtained during the screening period.
- •Currently enrolled and receiving an investigational agent in a clinical research study or received an investigational agent for any reason within 4 weeks prior to screening.
- •Require intermittent or chronic treatment with an anti-herpetic drug (e.g., acyclovir), other than intermittent topical use.
研究组 & 干预措施
Radiation/Cisplatin
Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.
干预措施: Radiation (Radiation)
Radiation/Cisplatin
Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.
干预措施: Cisplatin (Drug)
Talimogene Laherparepvec + Radiation/Cisplatin
The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ plaque-forming units (PFU)/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.
干预措施: Talimogene Laherparepvec (Biological)
Talimogene Laherparepvec + Radiation/Cisplatin
The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ plaque-forming units (PFU)/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.
干预措施: Radiation (Radiation)
Talimogene Laherparepvec + Radiation/Cisplatin
The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ plaque-forming units (PFU)/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.
干预措施: Cisplatin (Drug)
结局指标
主要结局
2-year Event-free Survival
时间窗: 2 years
Event-free survival is defined as the time from randomization until the first evidence of relapse, disease progression (local, regional, metastatic, or second primary), or death from any cause. Because this study was terminated with only 5 participants enrolled, and the study was terminated in the first year, this endpoint was not analyzed.
次要结局
- Clinical Objective Response (cOR)(End of trial; the maximum time on study was 20 weeks.)
- Metabolic Complete Response (mCR)(End of study; the maximum time on study was 20 weeks.)
- Pathologic Complete Response (mCR)(Up to Week 20)
- Time to Distant Failure(Up to 27 months)
- Time to Any Failure(Up to 27 months)
- Overall Survival(Up to 5 years after chemoradiotherapy)
- Disease-specific Survival(Up to 5 years after chemoradiotherapy)
- Time to Locoregional Failure(Up to 27 months)
- Participants With N1-2 Disease at Baseline Requiring Neck Dissection(Weeks 19 - 21)