Chemotherapy (Paclitaxel and Carboplatin)and Thoracic Radiotherapy With Swallowed Manganese Superoxide Dismutase (MnSOD) Plasmid Liposome Protection in Patients With Locally Advanced Stage III Non-Small Cell Lung Cancer: A Phase I-II Study
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Determination of Recommended Phase II Dose of MnSOD/Plasmid DNA
研究概览
简要总结
This is a Phase I-II study evaluating the feasibility, safety, and efficacy of swallowed MnSOD plasmid/liposome (PL) transgene given as protection against radiation-induced esophagitis during concurrent paclitaxel and carboplatin chemotherapy with thoracic radiation in subjects with locally advanced non-small cell lung cancer (NSCLC).
详细描述
This is a Phase I-II study evaluating the feasibility, safety, and efficacy of swallowed MnSOD plasmid/liposome (PL) transgene given as protection against radiation-induced esophagitis during concurrent paclitaxel and carboplatin chemotherapy with thoracic radiation in subjects with locally advanced non-small cell lung cancer (NSCLC). Phase I of the study will assess the feasibility and safety of MnSOD PL by dose escalation in 3 cohorts of 3 chemoradiotherapy subjects each (Cohort1 = 0.3 mg/dose, Cohort2 = 3 mg/dose, Cohort3 = 30 mg/dose). The highest dose completed (as determined by toxicity monitoring for 8 weeks from initial treatment) will be the starting dose for Phase II. Phase II will examine the efficacy of MnSOD PL by assessing the incidence of Grade 3 or 4 esophagitis in 27 additional chemoradiotherapy subjects. Incidence of esophageal toxicity, as well as clinical response to the combination of chemoradiotherapy with MnSOD PL are the outcomes of interest.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically documented NSCLC including squamous cell carcinoma, adenocarcinoma (including bronchoalveolar cell), and large cell anaplastic carcinoma (including giant and clear cell carcinomas) and poorly differentiated non-small cell lung cancer. Totally resected tumors are excluded.
- •Subjects must be without evidence of M
- •Subjects with T1 or T2 disease with N2 or tumor stage 3, lymph node metastasis 1-2 ( stage 1) disease (Stage IIIA) are eligible if they are medically inoperable. Subjects with T4 with any N or any T with N3 disease are eligible. Radiographic evidence of mediastinal lymph nodes >2.0 cm in the largest diameter is sufficient to stage N2 or N3 disease. If the largest mediastinal node is < 2.0 cm in diameter and this is the basis for stage III disease, then at least one of the nodes must be proven positive cytologically or histologically.
- •Subjects with tumors adjacent to a vertebral body are eligible as long as all gross disease can be encompassed in the radiation boost field. The boost volume must be limited to < 50% of the ipsilateral lung volume.
- •Subjects with a pleural effusion that is a transudate, cytologically negative and non-bloody are eligible if the radiation oncologists feel the tumor can still be encompassed within a reasonable field of radiotherapy. Exudative, bloody, or cytologically malignant effusions are ineligible. If a pleural effusion can be seen on the chest CT but not on chest X-ray and is too small to tap, the subject will be eligible.
- •Subjects must be deemed a suitable candidate for protocol treatment by both Radiation Oncology and Medical Oncology
- •Subjects must have a Performance Status > 70 (Karnofsky Performance Scale).
- •Subjects Weight loss < 10% in 3 months prior to diagnosis.
- •Subjects must be male or female > 18 years.
- •Subjects must have had no prior systemic chemotherapy, radiation therapy to the thorax, or total surgical resection.
- •At least 3 weeks since formal exploratory thoracotomy and the subject has recovered from surgery, or 1 week from diagnostic thoracoscopy.
- •Laboratory values must be as follows: (See Section 6.1 of the full protocol for required timing): Granulocytes > 2,000/ml, Platelets > 100,000/ml, Hemoglobin* > 8 mg/dl, Bilirubin < 1.5 x normal, Creatinine clearance > 50 ml/n (24 hour or calculated, forced expiratory volume at one second > 800 cc. Note: *Physician can maintain a subject's hemoglobin with the use of Erythropoetin or transfusions prophylactic use of G-CSF (colony stimulating factor, is not permitted).
- •Subjects must have a MRI or CT brain scan within 4 weeks prior to study entry to rule out asymptomatic brain metastases.
- •Subjects must be informed of the investigational nature of the study and sign an informed consent form and have no serious medical or psychiatric illnesses that would prevent informed consent.
- •No history of serious cardiac disease that is not adequately controlled.
- •Female subjects must be non-pregnant and non-lactating. Female subjects of childbearing potential must implement an effective method of contraception during the study. All women of childbearing potential must have a pre-study negative serum or urine pregnancy test within 7 days prior to study entry.
- •Exclusion Criteria
- •Inability to meet any of the above eligibility requirements
排除标准
- 未提供
研究组 & 干预措施
Radiation + MnSOD PL + Paclitaxel + Carboplatin
MnSOD PL (0.3, 3, or 30 mg) + (Paclitaxel + Carboplatin (45mg/m^2)) + Radiation 1.9-2.1 Gy daily 5 times per week (4-6 hr after the first MnSOD PL dose). The total dose planned at 77.0 Gy with a range of 69-84Gy in 34-38 fractions over 7-8 weeks.
干预措施: Manganese Superoxide Dismutase Plasmid Liposome (Genetic)
Radiation + MnSOD PL + Paclitaxel + Carboplatin
MnSOD PL (0.3, 3, or 30 mg) + (Paclitaxel + Carboplatin (45mg/m^2)) + Radiation 1.9-2.1 Gy daily 5 times per week (4-6 hr after the first MnSOD PL dose). The total dose planned at 77.0 Gy with a range of 69-84Gy in 34-38 fractions over 7-8 weeks.
干预措施: carboplatin (Drug)
Radiation + MnSOD PL + Paclitaxel + Carboplatin
MnSOD PL (0.3, 3, or 30 mg) + (Paclitaxel + Carboplatin (45mg/m^2)) + Radiation 1.9-2.1 Gy daily 5 times per week (4-6 hr after the first MnSOD PL dose). The total dose planned at 77.0 Gy with a range of 69-84Gy in 34-38 fractions over 7-8 weeks.
干预措施: paclitaxel (Drug)
Radiation + MnSOD PL + Paclitaxel + Carboplatin
MnSOD PL (0.3, 3, or 30 mg) + (Paclitaxel + Carboplatin (45mg/m^2)) + Radiation 1.9-2.1 Gy daily 5 times per week (4-6 hr after the first MnSOD PL dose). The total dose planned at 77.0 Gy with a range of 69-84Gy in 34-38 fractions over 7-8 weeks.
干预措施: Radiation Therapy (Radiation)
结局指标
主要结局
Determination of Recommended Phase II Dose of MnSOD/Plasmid DNA
时间窗: Every 8 weeks, up to 2 years
The maximally tolerated dose (milligrams) defined as the highest dose with fewer than one-third of patients experiencing a dose-limiting toxicity (DLT) per CTCAE v3.0 due to MnSOD. (Three patients treated at each at three tiers of 0.3, 3, and 30mg of MnSOD/plasmid DNA. If no DLTs (grade III/IV toxicity due to MnSOD PL) observed, the dose of MnSOD PL escalated to the next tier. If one DLT observed, the cohort is expanded to six patients. If two of six patients experienced a DLT, dose escalation stops and the next lowest dose declared maximum tolerated dose (MTD). If none of three or one of six patients experience DLT at the 30-mg tier, that dose is defined as the starting dose for the efficacy phase and the MTD would be undefined).
Radiation-induced Esophageal Toxicity
时间窗: Up to 2 years
Number of patients experiencing grade III/IV esophageal toxicity per CTCAE v3.0.
次要结局
- Overall (Objective) Response(Up to 2 years)
- Overall Survival (OS)(Up to 5 years)
- Time to Disease Progression(Up to 5 years)
研究者
Joel Greenberger
Professor, Chairman of Radiation Oncology
University of Pittsburgh