Genomic Profiling in Recommending Treatment for Patients With Metastatic Solid Tumors

Study Overview
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Brief Summary
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This research trial studies using genomic profiling to recommend anticancer treatment to patients with cancer that has spread beyond the original site of the tumor (metastatic cancer). Genomic profiling studies the deoxyribonucleic acid (DNA) of a tumor to detect genetic changes or abnormalities. This information can then be used to recommend treatments that may be more likely to result in a beneficial response. It is not yet known whether genomic profiling will detect abnormalities that can be used to make treatment recommendations and whether treatment based on genomic profiling is more effective than standard treatment.

Detailed Description
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PRIMARY OBJECTIVES: I. Assess the feasibility of integrating tumor genomic profiling in the adult oncology clinic at the Stanford Cancer Institute. SECONDARY OBJECTIVES: I. Determine the percentage of tumors that harbor actionable genomic changes. II. Explore effects of individual molecular profiling including the percent of time that profiling changes the treatment. III. Determine the number of cases in which a genomically identified targeted therapy is available. IV. Determine the clinical benefit of genomic based therapy, as defined by: response rate (according to Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 response criteria); the percent of patients with non-progression at 4 months, and overall survival, in patients whose therapy is selected based on profiling. V. Determine if circulating free tumor DNA (ctDNA) in the blood stream (liquid biopsy) yields similar genomic results as the metastatic tumor analysis. VI. Determine if ctDNA analysis during treatment correlates with RECIST 1.1 criteria in predicting response. OUTLINE: Tissue samples are collected at baseline and blood for liquid biopsy is collected at baseline and every 6-8 weeks during active treatment. Tissue samples are analyzed via sequencing for tumor genomic profiling. After completion of active treatment, participants are followed up at 4, 8, 12, 18, and 24 months.

Official Title
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Tumor Genomic Profiling: A Personalized Medicine Approach

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Genetic: mutation analysis
* Other: cytology specimen collection procedure
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Understand and provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization prior to initiation of any study-specific procedures Have a diagnosis of metastatic, incurable cancer and have progressed on at least one line of systemic therapy OR a cancer with no standard 1st-line systemic therapy shown to prolong survival (or where a clinical trial recommended as the 1st-line option) Measurable disease (RECIST 1.1) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 In the opinion of the investigator, be medically suitable for and willing to undergo a biopsy or surgical procedure to obtain tissue as a part of routine care for their malignancy OR have adequate archival tissue from a previous biopsy available for profiling Female patients of childbearing potential must have a negative pregnancy test and agree to use at least one form of contraception during the study and for at least one month after treatment discontinuation; for the purposes of this study, child-bearing potential is defined as: all female patients that were not in post-menopause for at least one year or are surgically sterile Male patients must use a form of barrier contraception approved by the investigator/treating physician during the study and for at least one month after treatment discontinuation Exclusion Criteria: Have lesions that are not accessible to biopsy or not planned for biopsy as part of routine care OR if archival tissue will be used for profiling, an insufficient amount is available Have diagnosis of a hematologic malignancy Have symptomatic central nervous system (CNS) metastasis; patients with a history of CNS metastases who have been treated with whole brain irradiation must be stable without symptoms for 4 weeks after completion of treatment, with image documentation required, and must be either off steroids or on a stable dose of steroids for >= 2 weeks prior to enrollment Have uncontrolled concurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmias, psychiatric illness, or situations that would limit compliance with the study requirements or the ability to willingly give written informed consent Have known human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) infection Are pregnant or breast-feeding patients or any patient with childbearing potential not using adequate contraception

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 |
| --- | --- |
| Ancillary-correlative (tumor genomic profiling)<br>Tissue samples are collected at baseline and blood for liquid biopsy is collected at baseline and every 6-8 weeks during active treatment. Tissue samples are analyzed via sequencing for tumor genomic profiling. | Genetic: mutation analysis<br>* Correlative studies<br>Other: cytology specimen collection procedure<br>* Correlative studies<br>* Other names: cytologic sampling;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility, measured as the proportion of patients with at least one actionable alteration | An actionable alteration is defined as availability of targeted therapy, scored as: A) an FDA-approved drug, B) an FDA-approved drug in another tumor type, or C) a drug that is not yet approved but has a clinical trial open. The percentage of patients in the profile arm with successful profiling will be calculated and further characterized by availability category. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drugs (if any) that target alterations found in a patient's tumor material at baseline, as identified by the Molecular Tumor Board |  | Baseline | 
| Drugs (if any) that target alterations found in a patient's peripheral blood at baseline, as identified by the Molecular Tumor Board |  | Baseline | 
| Availability of targeted therapy from tumor material scored as category A, B, or C above or D) No target therapy available, or no genetic alterations found |  | Baseline | 
| Overall survival | Overall survival of patients in each cohort will be characterized using Kaplan-Meier plots and the two cohorts will be compared using a Cox model to control for age and sex. | Number of days from enrollment to death, assessed up to 24 months | 
| Clinical response rate, assessed according to RECIST 1.1 criteria | Response will be compared using logistic regression, adjusting for the same risk factors. | Up to 24 months | 
| Incidence of adverse events | Categorized by grade and MedDRA preferred term. | Up to 30 days after last dose of active treatment | 
| Tumor-based genomics | Comparison of tumor-based genomics with peripheral-blood genomics will be carried out by comparing the list of genetic aberrations found in the two different samples (tumor vs ctDNA) and possible target drugs identified from each source. Agreement on success of profiling will be assessed using a kappa statistic. | Baseline | 
| Peripheral-blood genomics | Comparison of tumor-based genomics with peripheral-blood genomics will be carried out by comparing the list of genetic aberrations found in the two different samples (tumor vs ctDNA) and possible target drugs identified from each source. Agreement on success of profiling will be assessed using a kappa statistic. | Baseline |