Multicenter, Open-Ended, Double-Blind, Placebo-Controlled, Phase III Study of AE-941 in Addition to Combined Modality Treatment (Chemotherapy/Radiotherapy) for Locally Advanced Unresectable Non-Small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 756
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells. AE-941 may help shrink or slow the growth of non-small cell lung cancer cells. It is not yet known if combination chemotherapy plus radiation therapy is more effective with or without AE-941 for non-small cell lung cancer. This randomized phase III trial is studying combination chemotherapy and radiation therapy given with AE-941 to see how well they work compared to combination chemotherapy and radiation therapy alone in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery
详细描述
PRIMARY OBJECTIVES:
I. Determine the overall survival of patients with unresectable stage IIIA or IIIB non-small cell lung cancer treated with induction platinum-based chemotherapy and radiotherapy with or without AE-941 (Neovastat).
II. Determine the progression-free survival, tumor response, tumor response duration, and metastasis-free survival of patients treated with these regimens.
III. Determine the tolerability of this regimen in these patients.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to stage (IIIA vs IIIB), type of platinum-based induction chemotherapy to be received (cisplatin and vinorelbine vs carboplatin and paclitaxel), and gender. Patients are randomized to 1 of 2 treatment arms.
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
- Double (Participant, Investigator)
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 confirmed newly diagnosed, untreated, unresectable stage IIIA or stage IIIB non-small cell lung cancer
- •Squamous cell carcinoma, adenocarcinoma, or large cell carcinoma of the lung
- •Mixed tumors allowed if non-small cell elements identified
- •Contralateral supraclavicular and/or scalene lymph node involvement allowed
- •No disease extending into the cervical region
- •At least 1 bidimensionally or unidimensionally measurable lesion
- •No pleural effusion unless cytologically negative or too small to safely aspirate
- •Not scheduled for curative cancer surgery
- •Performance status - ECOG 0-1
- •Absolute neutrophil count greater than 1,500/mm^3
- •Platelet count greater than 100,000/mm^3
- •Hematocrit greater than 30%
- •SGOT or SGPT less than 1.5 times upper limit of normal
- •Bilirubin normal
- •Creatinine less than 1.5 mg/dL
- •Creatinine clearance greater than 60 mL/min
- •No other major medical or psychiatric illness that would preclude study participation or consent
- •No medical condition that interferes with oral medication intake and/or absorption (gastrectomy or major intestinal resection)
- •No grade 2 or greater peripheral neuropathy unless secondary to mechanical etiology
- •No hypersensitivity to fish products
- •No more than 10% weight loss within past 3 months
- •No other malignancy within past 3 years except inactive carcinoma in situ of the cervix or nonmelanoma skin cancer
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •At least 30 days since prior chemotherapy
- •See Disease Characteristics
- •Recovered from prior major surgery
- •At least 30 days since prior shark cartilage products
- •No other concurrent investigational anticancer agents
- •No other concurrent cartilage products
- •No other concurrent investigational agents
- •No concurrent amifostine or other radioprotectants
- •No concurrent enrollment in other clinical trials
排除标准
- 未提供
研究组 & 干预措施
Arm I (shark cartilage extract AE-941)
Patients receive oral AE-941 (Neovastat) twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.
All patients receive induction chemotherapy with 1 of the following platinum-based regimens: cisplatin IV on days 1, 22, 50, and 71 and vinorelbine IV on days 1, 8, 22, 29, 50, 57, 71, and 78 carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on days 1, 22, 50, 57, 64, 71, 78, and 85.
All patients receive radiotherapy beginning on day 50 for 6 weeks. Treatment in both arms continues in the absence of unacceptable toxicity.
干预措施: shark cartilage extract AE-941 (Drug)
Arm I (shark cartilage extract AE-941)
Patients receive oral AE-941 (Neovastat) twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.
All patients receive induction chemotherapy with 1 of the following platinum-based regimens: cisplatin IV on days 1, 22, 50, and 71 and vinorelbine IV on days 1, 8, 22, 29, 50, 57, 71, and 78 carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on days 1, 22, 50, 57, 64, 71, 78, and 85.
All patients receive radiotherapy beginning on day 50 for 6 weeks. Treatment in both arms continues in the absence of unacceptable toxicity.
干预措施: cisplatin (Drug)
Arm I (shark cartilage extract AE-941)
Patients receive oral AE-941 (Neovastat) twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.
All patients receive induction chemotherapy with 1 of the following platinum-based regimens: cisplatin IV on days 1, 22, 50, and 71 and vinorelbine IV on days 1, 8, 22, 29, 50, 57, 71, and 78 carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on days 1, 22, 50, 57, 64, 71, 78, and 85.
All patients receive radiotherapy beginning on day 50 for 6 weeks. Treatment in both arms continues in the absence of unacceptable toxicity.
干预措施: vinorelbine tartrate (Drug)
Arm I (shark cartilage extract AE-941)
Patients receive oral AE-941 (Neovastat) twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.
All patients receive induction chemotherapy with 1 of the following platinum-based regimens: cisplatin IV on days 1, 22, 50, and 71 and vinorelbine IV on days 1, 8, 22, 29, 50, 57, 71, and 78 carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on days 1, 22, 50, 57, 64, 71, 78, and 85.
All patients receive radiotherapy beginning on day 50 for 6 weeks. Treatment in both arms continues in the absence of unacceptable toxicity.
干预措施: carboplatin (Drug)
Arm I (shark cartilage extract AE-941)
Patients receive oral AE-941 (Neovastat) twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.
All patients receive induction chemotherapy with 1 of the following platinum-based regimens: cisplatin IV on days 1, 22, 50, and 71 and vinorelbine IV on days 1, 8, 22, 29, 50, 57, 71, and 78 carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on days 1, 22, 50, 57, 64, 71, 78, and 85.
All patients receive radiotherapy beginning on day 50 for 6 weeks. Treatment in both arms continues in the absence of unacceptable toxicity.
干预措施: paclitaxel (Drug)
Arm I (shark cartilage extract AE-941)
Patients receive oral AE-941 (Neovastat) twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.
All patients receive induction chemotherapy with 1 of the following platinum-based regimens: cisplatin IV on days 1, 22, 50, and 71 and vinorelbine IV on days 1, 8, 22, 29, 50, 57, 71, and 78 carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on days 1, 22, 50, 57, 64, 71, 78, and 85.
All patients receive radiotherapy beginning on day 50 for 6 weeks. Treatment in both arms continues in the absence of unacceptable toxicity.
干预措施: radiation therapy (Radiation)
Arm II (placebo)
Patients receive oral placebo twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.
All patients receive induction chemotherapy with 1 of the following platinum-based regimens: cisplatin IV on days 1, 22, 50, and 71 and vinorelbine IV on days 1, 8, 22, 29, 50, 57, 71, and 78 carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on days 1, 22, 50, 57, 64, 71, 78, and 85.
All patients receive radiotherapy beginning on day 50 for 6 weeks. Treatment in both arms continues in the absence of unacceptable toxicity.
干预措施: placebo (Other)
Arm II (placebo)
Patients receive oral placebo twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.
All patients receive induction chemotherapy with 1 of the following platinum-based regimens: cisplatin IV on days 1, 22, 50, and 71 and vinorelbine IV on days 1, 8, 22, 29, 50, 57, 71, and 78 carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on days 1, 22, 50, 57, 64, 71, 78, and 85.
All patients receive radiotherapy beginning on day 50 for 6 weeks. Treatment in both arms continues in the absence of unacceptable toxicity.
干预措施: cisplatin (Drug)
Arm II (placebo)
Patients receive oral placebo twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.
All patients receive induction chemotherapy with 1 of the following platinum-based regimens: cisplatin IV on days 1, 22, 50, and 71 and vinorelbine IV on days 1, 8, 22, 29, 50, 57, 71, and 78 carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on days 1, 22, 50, 57, 64, 71, 78, and 85.
All patients receive radiotherapy beginning on day 50 for 6 weeks. Treatment in both arms continues in the absence of unacceptable toxicity.
干预措施: vinorelbine tartrate (Drug)
Arm II (placebo)
Patients receive oral placebo twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.
All patients receive induction chemotherapy with 1 of the following platinum-based regimens: cisplatin IV on days 1, 22, 50, and 71 and vinorelbine IV on days 1, 8, 22, 29, 50, 57, 71, and 78 carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on days 1, 22, 50, 57, 64, 71, 78, and 85.
All patients receive radiotherapy beginning on day 50 for 6 weeks. Treatment in both arms continues in the absence of unacceptable toxicity.
干预措施: carboplatin (Drug)
Arm II (placebo)
Patients receive oral placebo twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.
All patients receive induction chemotherapy with 1 of the following platinum-based regimens: cisplatin IV on days 1, 22, 50, and 71 and vinorelbine IV on days 1, 8, 22, 29, 50, 57, 71, and 78 carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on days 1, 22, 50, 57, 64, 71, 78, and 85.
All patients receive radiotherapy beginning on day 50 for 6 weeks. Treatment in both arms continues in the absence of unacceptable toxicity.
干预措施: paclitaxel (Drug)
Arm II (placebo)
Patients receive oral placebo twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.
All patients receive induction chemotherapy with 1 of the following platinum-based regimens: cisplatin IV on days 1, 22, 50, and 71 and vinorelbine IV on days 1, 8, 22, 29, 50, 57, 71, and 78 carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on days 1, 22, 50, 57, 64, 71, 78, and 85.
All patients receive radiotherapy beginning on day 50 for 6 weeks. Treatment in both arms continues in the absence of unacceptable toxicity.
干预措施: radiation therapy (Radiation)
结局指标
主要结局
Overall survival
时间窗: From randomization until date of death or last follow-up, assessed up to 7 years
Survival distributions will be compared by use of the log-rank test. The stratified log-rank test (nominal or categorical covariates) may be used to simultaneously control for important prognostic factors. Kaplan-Meier curves will also be plotted to illustrate the comparative survival experience of both groups over the entire study period.
次要结局
- Progression-free survival every 3 months(From randomization until disease progression, assessed up to 7 years)
- Tumor response rate(Up to 7 years)
- Tumor response duration(From first observation of at least a partial response to detection of disease progression or death due to any cause, assessed up to 7 years)
- Metastasis-free survival(From randomization until metastasis documented by imaging procedures, assessed up to 7 years)