Personalized Patient Derived Xenograft (pPDX) Modeling to Test Drug Response in Matching Host

Официальное название

Prospective Evaluation of Freshly Implanted Cancers in Mice to Test Drug Response in Matching Host

Обзор

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

Подробное описание

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.

Вмешательства

• Другое Molecular Profiling & In Vivo drug testing in pPDX and organoid cultures
  Molecular profiling of host tumour sample and pPDX will be performed and analyzed by an expert panel. In vitro organoid culture generation may also be performed if sufficient fresh tissue is available. Matched treatment recommendation based on profiling and in vivo pPDX drug testing results will be made, if available. This recommendation will be communicated to the primary oncologist.

Первичные конечные точки

• Measure of drug sensitive pPDX to a panel of drugs as a predictor of clinical response in matched host [Срок оценки: up to 5 years]
• Rate of results reporting [Срок оценки: up to 5 years]
• Rate of pPDX engraftment [Срок оценки: up to 2 years]

Вторичные конечные точки (3)

• Comparison of actionable alterations identified in clinical and pPDX samples [Срок оценки: up to 5 years]
• Number of patients with molecular abnormalities in pPDX as identified via NGS eliciting clinical responses while receiving matched treatments. [Срок оценки: up to 5 years]
• Correlation between pPDX and organoid drug sensitivities [Срок оценки: up to 5 years]

Критерии участия

Критерии включения

• 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

OR

(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

OR

(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

OR

(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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Канада · 1 центр

• Princess Margaret Cancer Centre — Toronto

Идентификаторы

NCT: NCT02732860 · REFLECT-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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