Prospective Evaluation of Freshly Implanted Cancers in Mice to Test Drug Response in Matching Host
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Measure of drug sensitive pPDX to a panel of drugs as a predictor of clinical response in matched host
研究概览
简要总结
By obtaining clinical specimens from participants with triple negative breast cancer (TNBC), colorectal cancer (CRC), high grade serous ovarian cancer (HGSOC), and other select tumor types to establish and profile as freshly implanted tumors in mice, the aim of this study is to identify agents with predicted activity in the host patient while also potentially providing them with personalized cancer treatment options
详细描述
Personalized patient-derived xenografts (pPDX) are increasingly used as tools for drug development in pre-clinical settings, and have been shown to recapitulate the histology and behavior of the cancers from which they are derived. Although, they have been commonly used productively as pre-clinical disease models to study disease biology and drug response, they have not been used prospectively to inform clinical management. pPDX have been employed to inform clinical decision-making in small studies, which have shown high concordance between individual pPDX and patient responses to therapy. While encouraging, the role of this approach in breast, colorectal, ovarian, and other cancer populations and in the context of genomic drug matching strategies remains undefined. This has created an opportunity to evaluate the utility of pPDX as clinical predictors to direct the use of chemo- and targeted therapies in combination with comprehensive genomic and epigenetic analysis for patients with TNBC, CRC, HGSOC and other selected tumor types.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Age > 18 years.
- •Patient diagnosis must be categorized as either (I) OR (II) OR (III) OR (IV):
- •(I) Histologically confirmed Triple Negative Breast Cancer by Institutional and American Society of Clinical Oncology (ASCO)/Cancer of American Pathologists (CAP) guidelines, either:
- •Stage IV (metastatic) disease that has not been treated with systemic therapy in the metastatic setting or
- •Stage I to III (non-metastatic) with residual mass by clinical exam and/or breast imaging following anthracycline + taxane-containing neoadjuvant chemotherapy
- •(II) Histologically-confirmed Stage IV colorectal cancer treated with ≤ 1 line of systemic therapy in the metastatic setting, either:
- •Undergoing surgical resection of liver metastases or
- •With metastatic lesions amenable to biopsy
- •(III) Histologically-confirmed advanced High Grade Serous Ovarian Cancer, either:
- •Recurrent disease with a life expectancy of at least 12 months or
- •Stage III or IV with residual disease following neoadjuvant chemotherapy, or at risk of high recurrence
- •(IV) Histologically confirmed solid tumor not meeting criteria for (I), (II) or (III) above, for which evaluation of investigational therapies is of particular interest or where clinical need exists, at the discretion of the PI
- •Disease amenable to biopsy or surgery for tissue procurement
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Willingness and ability of patient to provide signed voluntary informed consent.
排除标准
- •Clinically significant hepatic, renal, cardiac or other organ dysfunction likely to limit participation in clinical trials.
- •Known brain metastasis
- •Any condition that could interfere with a patient's ability to provide informed consent such as dementia or severe cognitive impairment.
- •Any contraindication to undergoing a biopsy procedure.
研究组 & 干预措施
Triple Negative Breast Cancer
Triple negative breast cancer patients with residual invasive disease following neoadjuvant chemotherapy (n= up to 15) or with newly diagnosed metastatic disease (n=up to 30).
After the screening procedures confirms patient eligibility:
- Molecular Profiling will be performed on clinical sample
- pPDX generation for in vivo drug testing
- In vitro organoid culture generation (if sufficient fresh tissue available)
- Identifying an actionable genomic alteration and drug making a matched treatment therapy recommendation.
干预措施: Molecular Profiling & In Vivo drug testing in pPDX and organoid cultures (Other)
Colorectal Cancer
Colorectal cancer patients with metastatic disease undergoing resection of liver metastases, or with lesions amenable to biopsy (n=up to 15).
After the screening procedures confirms patient eligibility:
- Molecular Profiling will be performed on clinical sample
- pPDX generation for in vivo drug testing
- In vitro organoid culture generation (if sufficient fresh tissue available)
- Identifying an actionable genomic alteration and drug making a matched treatment therapy recommendation.
干预措施: Molecular Profiling & In Vivo drug testing in pPDX and organoid cultures (Other)
High Grade Serous Ovarian Cancer
High grade serous ovarian cancer patients with recurrent disease with a life expectancy of at least 12 months (n=up to 15), or Stage III or IV with residual disease following neoadjuvant chemotherapy, or at risk of high recurrence (n=up to 15).
After the screening procedures confirms patient eligibility:
- Molecular Profiling will be performed on clinical sample
- pPDX generation for in vivo drug testing
- In vitro organoid culture generation (if sufficient fresh tissue available)
- Identifying an actionable genomic alteration and drug making a matched treatment therapy recommendation.
干预措施: Molecular Profiling & In Vivo drug testing in pPDX and organoid cultures (Other)
Other tumor types
Other selected tumor types at the discretion of the PI (n= up to 30)
After the screening procedures confirms patient eligibility:
- Molecular Profiling will be performed on clinical sample
- pPDX generation for in vivo drug testing
- In vitro organoid culture generation (if sufficient fresh tissue available)
- Identifying an actionable genomic alteration and drug making a matched treatment therapy recommendation.
干预措施: Molecular Profiling & In Vivo drug testing in pPDX and organoid cultures (Other)
结局指标
主要结局
Measure of drug sensitive pPDX to a panel of drugs as a predictor of clinical response in matched host
时间窗: up to 5 years
Sensitivity measured by tumor growth inhibition (\>80%) or objective tumor response (regression) as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria.
Rate of results reporting
时间窗: up to 5 years
Rate of pPDX engraftment
时间窗: up to 2 years
次要结局
- Comparison of actionable alterations identified in clinical and pPDX samples(up to 5 years)
- Number of patients with molecular abnormalities in pPDX as identified via NGS eliciting clinical responses while receiving matched treatments.(up to 5 years)
- Correlation between pPDX and organoid drug sensitivities(up to 5 years)