Genomic Profiling in Recommending Treatment for Patients With Metastatic Solid Tumors

Recruiting

• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Interventions: Genetic: mutation analysis; Other: cytology specimen collection procedure; Other: laboratory biomarker analysis

• Registration Number: NCT02215928
• Lead Sponsor: Stanford University

Brief Summary

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

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.

Study Timeline

• Study Start: 2014-07-28
• Study First Submitted: 2014-08-11
• Study First Submitted QC: 2014-08-11
• Study First Posted: 2014-08-13
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-17
• Last Update Posted: 2024-12-18
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Ancillary-correlative (tumor genomic profiling)	mutation analysis	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.
Ancillary-correlative (tumor genomic profiling)	laboratory biomarker analysis	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.
Ancillary-correlative (tumor genomic profiling)	cytology specimen collection procedure	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.

Primary Outcome Measures

Name	Time	Method
Feasibility, measured as the proportion of patients with at least one actionable alteration	Baseline	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.

Secondary Outcome Measures

Name	Time	Method
Overall survival	Number of days from enrollment to death, assessed up to 24 months	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.
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
Clinical response rate, assessed according to RECIST 1.1 criteria	Up to 24 months	Response will be compared using logistic regression, adjusting for the same risk factors.
Incidence of adverse events	Up to 30 days after last dose of active treatment	Categorized by grade and MedDRA preferred term.
Tumor-based genomics	Baseline	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.
Drugs (if any) that target alterations found in a patient's tumor material at baseline, as identified by the Molecular Tumor Board	Baseline
Peripheral-blood genomics	Baseline	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.

Trial Locations

Locations (1)

Stanford University; 🇺🇸 Palo Alto, California, United States