TREATMENT RESISTANCE FOLLOWING ANTI-CANCER THERAPIES (TRANSLATE)
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 38
- 试验地点
- 62
- 主要终点
- Change in the Frequency of Gene Alterations Between Pre-treatment Tumor Samples (Archival) and Post-progression (De Novo) Tumor Biopsies
研究概览
简要总结
The TRANSLATE study aims to better understand why tumors become resistant to standard anti-cancer therapies.
New tumor biopsy and blood samples are collected after disease progression on standard-of-care anti-cancer treatment and compared to the initial (archival) tumor biopsy sample taken from the same patient.
Annotated reports of results from clinical Next Generation Sequencing (NGS) gene panel tests of both tumor and blood are sent directly from the testing lab to the study physician for discussion with the patient during the study.
Patients may participate in interventional treatment clinical trials at the same time as participating in the TRANSLATE study.
Primary data will be publicly available after the study to support further research.
详细描述
Background: Development of new cancer treatments requires better understanding of why tumors develop resistance to standard-of-care (SOC) therapies. However, post-progression tumor biopsies are not routinely collected, limiting the tissue available to characterize mechanisms of treatment resistance. The TRANSLATE clinical study is specifically designed to address these critical gaps.
Trial design: TRANSLATE is a global, multicenter, translational study designed to collect and compare archival pre-treatment tumor tissue with paired de novo tumor and blood samples obtained following disease progression on SOC therapies, targeting therapeutically important areas of cancer biology.
Eligible Tumor Type and Most Recent SOC Therapy:
- Non-small-cell lung and Anti-PD-1/-L1 monotherapy
- Non-small-cell lung and Anti-PD-1/-L1 + platinum
- Clear cell renal cell carcinoma and Anti-PD-1/-L1 monotherapy
- Clear cell renal cell carcinoma and Doublet anti-PD-1/-L1 + anti-CTLA-4
- Clear cell renal cell carcinoma and Pembrolizumab + axitinib
- Clear cell renal cell carcinoma and Avelumab + axitinib
- HR+ HER2- breast and Palbociclib + hormonal therapy
- germline mutated BRCA breast and Olaparib or talazoparib monotherapy
- Castration-resistant prostate and Enzalutamide
- Castration-resistant prostate and Abiraterone + prednisone
Eligibility criteria include adults with locally advanced or metastatic tumors; radiographic evidence of progressive disease during the most recent SOC regimen; sufficient archival tumor tissue; and a post-progression tumor lesion that is safely accessible for a new biopsy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 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
- •Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors treated as follows:
- •Non small cell lung carcinoma (NSCLC) monotherapy: Disease progression (PD) on 1st line monotherapy anti PD-1/ L
- •NSCLC combination: PD on 1st line anti PD-1/ L1 plus standard doublet platinum containing regimen; or PD on 1st-line anti-PD-1/-L1 plus standard doublet platinum-containing regimen followed by continuation of single agent anti-PD-1/-L1).
- •Renal cell carcinoma (RCC) with clear cell component: PD on 2nd line monotherapy anti PD-1/ L1; or PD on 1st line combination of doublet anti-PD-1/ L1 with anti-CTLA-4; or PD on 1st-line combination of avelumab with axitinib or pembrolizumab with axitinib.
- •HR+ HER2 adenocarcinoma of the breast: PD on 1st line combination of doublet palbociclib with hormonal therapy.
- •Castrate resistant adenocarcinoma of the prostate: PD on enzalutamide monotherapy.
- •Castrate resistant adenocarcinoma of the prostate: PD on abiraterone in combination with prednisone.
- •germline mutated BRCA (gBRCAm), HER2- breast cancer: PD on a PARP inhibitor monotherapy in patients previously treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting.
- •Radiographic evidence of PD, including the target lesion being subjected to biopsy for the study, on the most recent regimen that requires a change in anti-cancer treatment.
排除标准
- •Tumor biopsy taken from a bone or an irradiated target lesion.
- •Discontinuation of current or most recent anti cancer therapy due to toxicity and not progressive disease.
- •Initiation of new anti-cancer therapy after disease progression prior to planned biopsy.
结局指标
主要结局
Change in the Frequency of Gene Alterations Between Pre-treatment Tumor Samples (Archival) and Post-progression (De Novo) Tumor Biopsies
时间窗: Through study completion, approximately 3 months
Change in frequency is calculated by (frequency in de novo samples) - (frequency in archival samples). The frequency of each gene alteration is calculated as number of patients who harbored the alteration divided by the total number of patients in the cohort. Only gene alterations with variant allele frequency of 5% or greater were included in the analysis. Two different sequencing techniques were applied so 2 analysis sets were repeated for each cohort: targeted panel next-generation sequencing (NGS) and whole exome sequencing NGS.
次要结局
- Number of Participants With Fully Evaluable Archival and Post-Progression Tumor Biopsy by Cohort(Through study completion, approximately 3 months)
- Overall Agreement Rate of Gene Alterations Between Post-Progression Tumor Biopsy and Blood NGS Results(Through study completion, approximately 3 months)
- Change in Frequency of RB1 Gene Alterations Between Pre-Treatment Archival and Post-Progression Samples(Through study completion, approximately 3 months)
- Percentage of Participants Who Carried the RB1 Gene Alterations in Post-Progression Blood cfDNA(Through study completion, approximately 3 months)
- Change in Frequency of AR Gene Alterations Between Pre-Treatment Archival and Post-Progression Samples(Through study completion, approximately 3 months)
- Percentage of Participants Who Carried the AR Gene Alterations in Post-Progression Blood cfDNA(Through study completion, approximately 3 months)
- Change in Expression of Nuclear Hormone Receptors Between Pre-Treatment Archival and Post-Progression Samples(Through study completion, approximately 3 months)