A Phase 1-2 Study of Weekly OGX-011 Plus a Gemcitabine/Platinum-Based Regimen in Patients With Stage IIIB or IV Non Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 85
- 试验地点
- 22
- 主要终点
- Objective Response Rate of OGX-011 in Combination With Gemcitabine/Platinum-based Regimen
研究概览
简要总结
This clinical study will help determine if giving OGX-011 (custirsen sodium) in combination with gemcitabine (GEM) and cisplatin (CIS) or carboplatin (CARB) is a safe and effective treatment for patients with lung cancer. This study will help to assess the safety and anti-tumor effect of OGX-011 when given to patients in combination with GEM and CIS/CARB.
详细描述
OGX-011 is an experimental drug that has been shown to increase the effectiveness of commonly used cancer therapies such as chemotherapy, radiation and hormone therapy in several kinds of cancer types in animals. OGX-011 is being studied in the treatment of cancer patients in combination with chemotherapy. In humans, OGX-011 in combination with hormone therapy has been shown to decrease the tissue levels of a protein called clusterin, which can be overproduced in cancer cells. Clusterin has been found to block cell death and makes cells more resistant to cancer therapy. Gemcitabine (GEM), cisplatin (CIS) and carboplatin (CARB) have been approved by Health Canada and the Food and Drug Administration in the United States for the treatment of patients with lung cancer.
OGX-011 was administered as a 2-hr intravenous (IV) infusion on Days -7, -5, and -3 prior to Cycle 1, then weekly on Days 1, 8, 15 of each 21-day cycle; GEM was infused IV after OGX-011 on Days 1 and 8; either CIS or CARB was infused IV after GEM on Day 1 of each cycle. Six cycles of treatment were planned. Most patients received OGX-011 at 640 mg, but 3 patients received OGX-011 at 480 mg dose; OGX-011 dose groups were combined due to the small number of patients who received 480 mg.
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
- •Patients must have a histologically or cytologically confirmed diagnosis of NSCLC and must not have had chemotherapy or biological therapy for their disease.
- •Stage IIIB (N3 and/or pleural or pericardial effusion) or IV disease that is not amenable to either surgery or radiation therapy of curative intent.
- •Life expectancy of ≥ 12 weeks
- •If patient has had prior radiation therapy: lesion(s) used for determination of response was not previously irradiated or has increased in size since the completion of radiotherapy; and patient has recovered from any toxicity from the radiotherapy.
- •Radiotherapy to lesion(s) used for determination of response was completed at least 6 weeks prior to treatment; radiotherapy to other sites was completed at least 2 weeks prior to treatment.
- •At least one unidimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumors [RECIST] (at least 10 mm in longest diameter by spiral computed tomography [CT] scan, or at least 20 mm by standard techniques).
- •ECOG status must be ≤ 1
排除标准
- •Prior chemotherapy or biological therapy (approved or experimental) for NSCLC, including adjuvant and neoadjuvant treatment.
- •Presence of central nervous system (CNS) metastases, unless the patient has completed successful local therapy for CNS metastases, with the exception of leptomeningeal disease for which patients will be excluded. Patients must be off corticosteroids for at least 21 days prior to starting treatment.
- •Second primary malignancy (except in situ carcinoma of the cervix, adequately treated non-melanomatous skin cancers, clinically localized prostate cancer, superficial bladder cancer or other malignancy treated at least 3 years previously with no evidence of recurrence).
- •Patients eligible for combined modality therapy with curative intent as defined by the combination of chemotherapy, radiation therapy and/or surgery. (This criteria is intended to exclude patients with stage IIIB disease, as defined by the presence of N3 nodal status, who have been reported to have cure rates as high as 10% when treated with combined modality therapy.)
结局指标
主要结局
Objective Response Rate of OGX-011 in Combination With Gemcitabine/Platinum-based Regimen
时间窗: Based on assessments at baseline and after Cycles 2, 4, and 6. All subjects were followed for survival for a minimum of 3 years after the first dose of OGX-011 or until death.
Per RECIST Criteria V 1.0 and based on radiographic evaluations a subject was defined as having an objective response (OR) if the subject achieved either a confirmed partial response (PR) or confirmed complete response (CR). The evaluations were conducted after every two cycles of treatment for a maximum of 6 cycles. CR: disappearance of clinical/radiological evidence of tumor. PR: \>= 30% decrease in the sum of the longest diameter of target lesions. SD: did not fulfill the criteria for CR or PR but not progressive disease.
次要结局
- Progression-free Survival(All subjects were followed for a minimum of 3 years after the first dose of OGX-011 or until death.)
- Overall Survival(All subjects were followed for a minimum of 3 years after the first dose of OGX-011 or until death.)
- Effect of OGX-011 on Serum Clusterin Levels(Blood samples were collected at baseline and prior to infusion on Cycle 2 Day 1 and Cycle 3 Day 1)
- Cmax of OGX-011(Blood samples were collected as follows. Cycle 1; Day 1: pre-dose, 2 h (EOI), 0.5 h, 1 hr, 1.5 h, 2.5 h, 4 h, 6.5 h and 23.5 h post end of OGX-011 infusion, Day 22: pre-dose Cycle 2.)
- t1/2 of OGX-011(Blood samples were collected as follows. Cycle 1; Day 1: pre-dose, 2 h (EOI), 0.5 h, 1 hr, 1.5 h, 2.5 h, 4 h, 6.5 h and 23.5 h post end of OGX-011 infusion, Day 22: pre-dose Cycle 2.)
- AUC-0-last(Blood samples were collected as follows. Cycle 1; Day 1: pre-dose, 2 h (EOI), 0.5 h, 1 hr, 1.5 h, 2.5 h, 4 h, 6.5 h and 23.5 h post end of OGX-011 infusion, Day 22: pre-dose Cycle 2.)