Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Immune System Diseases

Rare Diseases

Breast Neoplasms

Colorectal Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hypersensitivity

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Breast Diseases

Skin Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Hematinics

All Drugs and Chemicals

Liver Extracts

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.

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.

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.

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.

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.

Molecular Profiling & In Vivo drug testing in pPDX and organoid cultures

David Cescon, MD

Elizabeth Shah

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

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.

Whole Blood, formalin fixed paraffin embedded blocks, fresh tumor tissue, malignant effusion or ascites (if no tumor tissue available), archival tissue (if not enrolled in molecular profiling studies IMPACT/OCTANE)

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

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

Sensitivity measured by tumor growth inhibition (\>80%) or objective tumor response (regression) as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria.

Genomic alterations identified using the Ion Proton System for Next-Generation Sequencing (NGS).

Overall accuracy of clinical responses as assessed by RECIST criteria in patient tumor.

University Health Network, Toronto

Blood and Lymph Conditions

Hematologic Neoplasms

Hematologic Diseases

drug sensitivity testing of primary patient derived cancer cells

ex-vivo drug response assay

Sascha Dietrich, MD

This observational study evaluates if drug response testing can be performed within 7 days and analyzes the value of ex-vivo drug screening for hematological malignancies as a biomarker to predict outcome, clinical course and response to treatment.

Targeted treatments have revolutionized care of individual diseases. While a new generation of targeted drugs is emerging in leukemia and lymphoma it remains clinical reality that most genetic information is not used for therapeutic stratification. This is in part based on the shortcomings of traditional biomarker discovery within clinical trials, where throughput is limited in both, drug number and sample size. If it were possible to map the variable pathway dependencies and drug sensitivity patterns in individual patients it is likely to become an asset to identify genotype-phenotype associations, understand the underlying complexities of molecular networks and further precision medicine stratification.

To link clinical outcome and ex-vivo drug response assays, the investigators systematically measure pathway sensitivity and resistance of primary tumor cells ex-vivo using a diverse compound library for individual patients in need of treatment. By systematically analyzing ex-vivo drug response patterns, tumors should be functionally grouped, by response phenotype. While for the purpose of this study selection of a specific treatment will not be based on ex-vivo drug response assays, clinical response- and follow-up data of patients will be prospectively collected in parallel.

Blood samples, bonemarrow aspiration, tissue of lymphnodes

Systematic and Mechanism-based Approach to Rational Treatment Trials of Blood Cancer

Systematic and Mechanism-based Approach to Rational Treatment Trials of Blood Cancer (SMARTrial)

Patients' sample (blood, bonemarrow aspirate, tissue of lymphnode) will collected on day 0. Ex-vivo drug sensitivity testing will be performed.

Ex-vivo drug sensitivity categorizes drugs as sensitive/not sensitive. Results will be compared with clinical outcome of patient (response vs. stable disease as defined in the clinical response definition by protocol

prediction of time to next treatment by a mathematical model based on ex-vivo drug response testing

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Personalized Patient Derived Xenograft (pPDX) Modeling to Test Drug Response in Matching Host	NCT02732860	Colorectal Neop... Colorectal Canc... Breast Cancer Breast Neoplasm... Ovarian Cancer Ovarian Neoplas...	Molecular Profi...	18 Years -	University Health Network, Toronto
Systematic and Mechanism-based Approach to Rational Treatment Trials of Blood Cancer	NCT03488641	Hematologic Dis... Treatment	ex-vivo drug re...	18 Years -	German Cancer Research Center
Systematic and Mechanism-based Approach to Rational Treatment Trials of Blood Cancer	NCT03488641	Hematologic Dis... Treatment	ex-vivo drug re...	18 Years -	German Cancer Research Center

Spots Global Cancer Trial Database for drug sensitivity testing