A Phase 1/2 Study to Assess the Safety and Efficacy of Lorvotuzumab Mertansine in Combination With Carboplatin/Etoposide in Patients With Advanced Solid Tumors Including Extensive Stage Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 181
- 试验地点
- 47
- 主要终点
- Occurrence of Dose Limiting Toxicities (DLT)
研究概览
简要总结
The purpose of this study is to test safety and efficacy of this combination treatment (IMGN901, carboplatin and etoposide) in patients with solid tumors and extensive stage small cell lung cancer.
详细描述
Small-Cell Lung Cancer (SCLC) is a neuroendocrine cancer of the lung that is typically caused by smoking. Patients generally present with symptoms of cough, dyspnea, pain and weakness, and often have extensive disease at that time. It is estimated that 13% of lung cancers are SCLC in origin1. Approximately 28,530 new cases of SCLC were expected in 2009 based on an estimate of 219,440 new cases of any cancer of the lung in the US in 20092.
There are 2 stages of the disease: limited-stage disease (LD) and extensive-stage disease (ED). SCLC-LD is confined to a region of the chest (the hemithorax and mediastinum) that is more amenable to radiation therapy. Thirty percent (30%) of patients present with SCLC-LD. The remaining patients (70%) present with SCLC-ED, in which the disease has progressed outside this region of the chest. Common sites of metastatic disease include the contralateral lung, liver, adrenal glands, brain, bones and/or bone marrow3. Recurrence after therapy is typical. In the rare patient who has longer-term survival, secondary malignancies (new SCLC tumors and other malignancies) are common because of long-term exposure to carcinogens.
SCLC is very responsive to chemotherapy and radiation therapy, having response rates of up to 80%4-7. In limited stage disease, the standard treatment is 'combined-modality therapy' consisting of combination chemotherapy such as cisplatin plus etoposide followed by thoracic radiation therapy. Surgery is rarely used.
Despite high response rates, therapy is rarely curative due to high rates of recurrence and metastasis. Overall 5-year survival for SCLC patients is 4%5. SCLC-LD patients typically achieve median survival of 14 to 24 months after therapy, with a 2-year survival rate of 40% to 50%. This survival rate drops to about 20% at 5 years4-7. SCLC-ED patients achieve a median survival of 8 to 12 months on therapy8.
Patients will typically have recurrent disease after therapy. While many of these patients may be eligible for further chemotherapy, survival at this stage is usually less than 6 months.
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
- •Patients must be 18 years old
- •Patients must have been diagnosed with small-cell lung cancer (SCLC) and extensive disease
- •ECOG performance status of 0, 1, or 2
- •No prior systemic chemotherapy for the treatment of SCLC
排除标准
- •Pregnant or lactating females
研究组 & 干预措施
IMGN901 with carboplatin and etoposide
Patients will receive IMGN901 along with carboplatin and etoposide for up to 6 cycles and then be able to continue on IMGN901 alone until no further benefit or toxicity.
干预措施: IMGN901 (Drug)
Carboplatin and Etoposide
Patients will receive Carboplatin and etoposide for up to 6 cycles.
干预措施: Carboplatin and Etoposide (Drug)
结局指标
主要结局
Occurrence of Dose Limiting Toxicities (DLT)
时间窗: 21 days (Cycle 1)
The primary outcome measure for Phase I was to determine the maximum tolerated dose (MTD) and characterize the dose limiting toxicities (DLT) of IMGN901 when administered in combination with carboplatin/etoposide chemotherapy followed by IMGN901 alone in patients with solid tumors. For the purposes of dose escalation and determination of MTD, DLTs were defined as AEs or abnormal laboratory values related to study treatment which occurred in Cycle 1 of the Dose Escalation phase, including any AEs that resulted in failure to meet the criteria for re-treatment. The following events were considered DLTs (using the most current version of CTCAE): febrile neutropenia; Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding; ≥ Grade 3 peripheral neuropathy; ≥ Grade 3 vomiting, nausea, or diarrhea that persisted despite the use of optimal therapy; other ≥ grade 3 non-hematologic toxicity (with the exception of brief fatigue i.e. ≤ 72 hours and alopecia)
Maximum Tolerated Dose (MTD) of IMGN901
时间窗: 21 days (Cycle 1)
A primary outcome measure for Phase I was to determine the maximum tolerated dose (MTD) of IMGN901 when administered in combination with carboplatin/etoposide chemotherapy followed by IMGN901 alone in patients with solid tumors. The MTD was determined based on DLTs that occurred during Cycle 1.
Progression Free Survival (PFS) in Phase II
时间窗: From randomization to objective tumor progression or death (up to post-treatment follow-up 28 days after last dose, up to 22 months)
The primary outcome measure for Phase II was to determine the efficacy of IMGN901 in combination with carboplatin/etoposide chemotherapy as first-line treatment for patients with extensive stage small cell lung cancer. PFS was defined as the time from enrollment until objective tumor progression according to RECIST 1.1 or death on study due to any cause, whichever occurred first. Only the results from the experimental arm (IMGN901 + carboplatin + etoposide) are presented as the primary objective of this phase of the study was to compare PFS in the experimental arm (triplet combination) against historical PFS rates for carboplatin and etoposide. The control arm was planned primarily to reliably assess the safety of IMGN901 and to demonstrate whether the or not the historical assumptions regarding efficacy were confirmed.
次要结局
- Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From the first dose of study drug on Cycle 1, Day 1 until 28 days after the last study treatment (up to 22 months))
- Median Overall Survival (OS) in Phase II(From the time of enrollment until death on study due to any cause (up to post-treatment follow-up 28 days after last dose, up to 22 months))
- Progression Free Survival (PFS) Rate at 6 Months(6 months)
- Overall Survival (OS) Rate at 12 Months(12 months)