A Phase 1b/2 Study of PEP503 (Radioenhancer) With Radiotherapy in Combination With Concurrent Chemotherapy for Patients With Head and Neck Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Phase1 and 2: Evaluation of Safety profile of PEP503
研究概览
简要总结
It's a prospective, open-label, single arm, nonrandomized study of PEP503 in head and neck squamous cell carcinoma (HNSCC) patients.
- Escalation portion (Phase 1b):A 3 + 3 dose escalation study design will be adopted in this phase to identify the recommended intratumor injection volumes of PEP503.
- Expansion portion (Phase 2): Following confirmation of the recommended volumes, 18 additional patients will be enrolled at the recommended volume level to evaluate for safety and efficacy.
详细描述
Primary Objectives:
- Phase 1b (dose escalation portion): To assess the safety profile and determine the Dose Limiting Toxicity (DLT) and to define the recommended volumes (doses) of PEP503.
- Phase 2 (expansion portion): To evaluate the anti-tumor activity in terms of the rate of locoregional control at one year and to evaluate the safety profile.
Secondary Objectives:
- Phase 1b: To characterize the body kinetic profile of PEP503.
- Phase 2: Objective tumor response, progression free survival rate at 1 year and pathological response (pR).
The target population is composed by patients who have pathologically confirmed squamous cell carcinoma of oral cavity with disease clinically staged as T4b who are not candidates for surgical resection or T3-4 who decline surgery or medical inoperable, or oropharynx, hypopharynx, or larynx with disease clinical staged as T3-4, without metastasis disease. ECOG performance status 0 or 1 and adequate bone marrow, renal, and hepatic function.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed squamous cell carcinoma (SCC) of oral cavity, oropharynx, hypopharynx, or larynx
- •Locally advanced or recurrent disease of: Oral Cavity:T4b, N any, who are not candidates for surgical resection; or T3-4, N any, who decline surgery or medical inoperable; OR Oropharynx, hypopharynx, or larynx: T3-4, N any
- •No evidence of distant metastatic disease, as determined by a negative PET scan or CT scan
- •ECOG Performance Status 0 or 1
- •Adequate function of bone marrow, kidney and liver:
- •White Blood Cell (WBC) ≥ 3.0 x 109/l
- •Absolute neutrophil count (ANC) ≥ 1.5 x 109/l
- •Platelet count ≥ 100 x 109/l
- •Hemoglobin ≥ 9.0 g/dL
- •Creatinine within normal range, for dose level with tri-weekly cisplatin, estimated GFR ≥ 60 mL/min/1.73m2 or CrCl ≥ mL/min is also required
- •AST ≤ 2.5 x ULN, ALT ≤ 2.5 x ULN and Alkaline phosphatase (ALP) ≤ 2.5 x ULN
- •Bilirubin ≤ 1.5 x ULN
- •20 years of age or older
- •All female patients of childbearing potential must have negative urine pregnancy test within 7 days prior to study treatment with PEP
- •Fertile patients must agree to use effective contraception during the study
排除标准
- •Tumor ulceration combined with vascular risks
- •Prior radiotherapy to any area within the planned radiotherapy field
- •Uncontrolled intercurrent illness
- •Concurrent treatment with any other anticancer therapy
- •Participation in any investigational drug study within 4 weeks
- •Prior or concurrent non-head and neck malignancies, excluding adequately treated basal or squamous cell cancer of the skin, and in situ cervical cancer, and any other cancer from which the subject has been cancer free for 5 years
- •Patients unable to comply with scheduled visits and other study procedures.
- •Preexisting neuropathy ≥ Grade 2 (CTCAE)
- •Pre-existing hearing impairment > Grade 2 (CTCAE) for patients receiving cisplatin 100 mg/m2
- •History of allergic reaction to platinum product
研究组 & 干预措施
PEP503+Cisplatin+Radiotheraphy
Phase 1b: There are 6 levels (L1- 5% + 40mg/m2 weekly cisplatin, L2- 10% + 40mg/m2 weekly cisplatin, L3- 15% + 40mg/m2 weekly cisplatin, L4-22% + 100mg/m2 tri-weekly cisplatin, L3a- 15% + 100mg/m2 tri-weekly cisplatin, and L5- 33% + 100mg/m2 tri-weekly cisplatin) in this phase 1b study. Only primary tumor will receive PEP503 implementation via intratumor injection. A 3 + 3 dose escalation study design will be adopted in this phase to identify the recommended intratumor injection volumes of PEP503.
Phase 2: The recommended volume identified from phase 1b will be applied in phase 2 for both primary tumor and ≥ 3 cm lymph node lesions.
干预措施: PEP503 (Drug)
PEP503+Cisplatin+Radiotheraphy
Phase 1b: There are 6 levels (L1- 5% + 40mg/m2 weekly cisplatin, L2- 10% + 40mg/m2 weekly cisplatin, L3- 15% + 40mg/m2 weekly cisplatin, L4-22% + 100mg/m2 tri-weekly cisplatin, L3a- 15% + 100mg/m2 tri-weekly cisplatin, and L5- 33% + 100mg/m2 tri-weekly cisplatin) in this phase 1b study. Only primary tumor will receive PEP503 implementation via intratumor injection. A 3 + 3 dose escalation study design will be adopted in this phase to identify the recommended intratumor injection volumes of PEP503.
Phase 2: The recommended volume identified from phase 1b will be applied in phase 2 for both primary tumor and ≥ 3 cm lymph node lesions.
干预措施: Cisplatin (Drug)
PEP503+Cisplatin+Radiotheraphy
Phase 1b: There are 6 levels (L1- 5% + 40mg/m2 weekly cisplatin, L2- 10% + 40mg/m2 weekly cisplatin, L3- 15% + 40mg/m2 weekly cisplatin, L4-22% + 100mg/m2 tri-weekly cisplatin, L3a- 15% + 100mg/m2 tri-weekly cisplatin, and L5- 33% + 100mg/m2 tri-weekly cisplatin) in this phase 1b study. Only primary tumor will receive PEP503 implementation via intratumor injection. A 3 + 3 dose escalation study design will be adopted in this phase to identify the recommended intratumor injection volumes of PEP503.
Phase 2: The recommended volume identified from phase 1b will be applied in phase 2 for both primary tumor and ≥ 3 cm lymph node lesions.
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
Phase1 and 2: Evaluation of Safety profile of PEP503
时间窗: 24 months
Safety of PEP503, as intratumor injection schedule, activated by CCRT will be assessed in terms of incidence and severity of clinical and laboratory Adverse Events by NCI-CTCAE version 4.0
Phase 2: The rate of locoregional control at one year
时间窗: 24 months
To evaluate the rate of locoregional control at one year after PEP503 intratumor injection
Phase 1: Determination of the Recommended doses and the Dose Limiting Toxicities (DLT)
时间窗: 24 months
To determine the Recommended volumes and the Dose Limiting Toxicities (DLT) of PEP503 administered as intratumor injection, activated by CCRT
次要结局
- Phase 2: Pathological response (pR)(24 months)
- Phase 2: Evaluation of objective tumor response as per Response Evaluation Criteria in Solid Tumors (RECIST)(24 months)
- Phase 1: The body kinetic profile of PEP503(24 months)
- Phase 2: Evalution of progression free survival rate at 1 year(24 months)