Tumor Molecular Profiling in Early Phase Clinical Trials

Study Overview
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Brief Summary
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Prospective, single centre, non-interventional exploratory research project that will be conducted on biological material and health-related personal data collected.

Detailed Description
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Single center, two-parts pilot, prospective study to assess the role of molecular tumor profiling in supporting patient enrollment in early phase clinical trials. Part A: patients with solid tumors or lymphomas (n=40) who are potential candidates for early phase clinical trials will be offered to have their more recent archival tumor tissue analyzed for the presence of somatic genomic alterations with the pan-cancer NGS Ion TorrentTM OncomineTM Comprehensive Assay v3 platform. Part B: patients who have been enrolled in early phase clinical trials (estimated number: 16-18) will have their archival tumor tissue assessed with HTG EdgeSeq Oncology Biomarker Panel Assay for RNA-Seq to explore gene expression signatures and blood collected and stored to create a repository of samples (¨liquid biopsy¨) for future research with the aim to investigate the mutational profile of ctDNA at baseline and the acquisition of new mutations at the time of disease progression as a consequence of treatment exposure.

Official Title
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Molecular Characterization of Solid Tumors and Lymphomas to Optimize the Drug Development Process and Patients Enrollment in Early Phase Clinical Trials

Conditions
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Advanced Solid Tumor, Lymphoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients age at least 18 years. Patients with histological diagnosis of advanced solid tumor or lymphoma who are potential candidates for early phase clinical trials. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 Live expectancy of at least 6 months. Availability of FFPE archival tumor tissue from previous surgery or diagnostic biopsy adequate for molecular analysis. Ability to understand the patient information and study consent. Signed and dated written informed consent must be available before performing any study-related procedure. Willing and able to comply with study procedures Exclusion Criteria: Presence of any clinical (e.g. concomitant disease, clinically significant symptoms, or non-clinical (psychological or social) conditions that would not make the patient eligible for enrolment in an early phase clinical trial. Any other active malignancy (other than the one for which the subject is being assessed for trial option) that is progressing or requiring active treatment with the exception of basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of any site.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Part A<br>Upon confirmation of the suitability for NGS analysis of the selected tumor sample, tumor DNA will be extracted and molecular profile will be performed using the pan-cancer NGS Ion TorrentTM OncomineTM Comprehensive Assay v3 according to manufacturer's instructions | |
| Part B<br>FFPE tumor archival tissue will be used to perform RNA-Seq with NGS HTG EdgeSeq Oncology Biomarker Panel Assay using the HTG machine following the manufacture's protocol. Blood samples for liquid biopsy will be collected at two time points: 1) Any time after enrollment in an early clinical trial and before starting the investigational agent (1 x 10 ml blood sample in EDTA tube as source of normal DNA for comparative analysis; 2 x 10 ml blood samples in cell-free DNA BCT Tubes for ctDNA collection; 2) At the time of radiological or clinical tumor progression (2 x 10 ml blood samples in cell-free DNA BCT Tubes for ctDNA collection). Blood samples will be collected and stored to create a biobank of liquid biopsy for future analysis. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accrual rate in early phase clinical trials | Number of patients with available molecular profile enrolled per year | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Outcome | Response rate among patients with available molecular tumor profiling that have been enrolled in an early phase clinical trial | Two years | 
| Number of successful NGS-based DNA analysis performed on archival tissue | Type and frequency of mutations identified on archival tissue | Two years | 
| Number of NGS-based RNA-seq samples analyzed | Analysis performed on archival tissue | Two years | 
| Rate of stored samples | Number of blood samples collected and stored for ctDNA analysis | Two years |