The TEAM Trial (Tasigna Efficacy in Advanced Melanoma): A Phase II, Open Label, Multi-center, Single-arm Study to Assess the Efficacy of Tasigna ® in the Treatment of Patients With Metastatic and/or Inoperable Melanoma Harboring a c-Kit Mutation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 55
- 试验地点
- 15
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
The purpose of this study is to determine whether nilotinib is efficacious in the treatment of metastatic and/or inoperable melanoma harboring a c-Kit mutation.
详细描述
This trial began as a multi-center, randomized, Phase III, controlled trial for nilotinib vs (DTIC) dacarbazine to assess the efficacy and safety of nilotinib (400 mg bid) in patients with c-Kit mutated metastatic and/or inoperable melanoma. The study was open to patients with mucosal or acral melanoma.
Due to substantial difficulties identifying and recruiting eligible patients, the trial design was altered from a randomized, two-arm, Phase III study to a single-arm, Simon two-stage Phase II study with protocol Amendment 2 (27-Jul-2011). While the original protocol required the recruitment of 120 patients, this amendment required the study to recruit only 41 patients (patients randomized to nilotinib prior to Amendment 2 were to be counted in this total, but those randomized to dacarbazine ( DTIC ) DTIC were not). Patients randomized to DTIC were allowed to cross-over to nilotinib, either immediately or at the time of progression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 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 confirmed mucosal or acral
- •Presence of a c-Kit mutation of exon 9, 11 or 13, or mutations Y822D and mutations D820Y, Y823D of exon 17, as confirmed by the central laboratory
- •Stage III unresectable or stage IV disease
- •The presence of one or more measurable lesions as detected by radiological or photographic methods and assessed according to RECIST 1.
- •Lesions must have a size of at least 10mm at longest diameter (using a slice thickness of 5 mm)or double the slice thickness to be considered a target lesion. Target lesions should not be selected in previously irradiated fields unless there is clear evidence of progression
- •WHO performance status 0 - 2
排除标准
- •C-Kit mutation of exons 17(except mutations D820Y, Y822D or Y823D) or any other exon not allowed by the inclusion criteria
- •Patients with c-Kit amplifications only and no mutation
- •Patients with any history of brain metastases
- •Patients who have had any prior treatment with TKIs
- •Patients receiving medications or herbal extracts which interfere with nilotinib metabolism which are not discontinued by the time of the baseline visit
- •Acute or chronic liver or renal disease considered unrelated to melanoma
- •Other protocol-defined inclusion/exclusion criteria may have applied.
研究组 & 干预措施
Nilotinib
400 mg twice daily
干预措施: Nilotinib (Drug)
DTIC
850 mg/m2 IV every 3 weeks
干预措施: DTIC (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: End of study (up to 39 months)
ORR was defined as the proportion of participants with a best overall response (BOR) of a confirmed complete response or partial response (CR+PR) determined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0) based on local investigators' assessment (CT/MRI/photography). Per RECIST, CR: disappearance of all target lesions, all non-target lesions, and no new lesion; PR: a \>=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the baseline sum, no unequivocal progression of non-TLs, and no new lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments at least 4 weeks apart.
次要结局
- OS Rate(End of study (up to 39 months))
- Durable Overall Response Rate (DORR)(End of study (up to 39 months))
- Progression Free Survival (PFS)(End of study (up to 39 months))
- Overall Survival (OS)(End of study (up to 39 months))
- Disease Control Rate (DCR)(End of study (up to 39 months))
- PFS Rate(End of study (up to 39 months))
- Time to Objective Response (TOR)(End of study (up to 39 months))