Genomic Profiling in Recommending Treatment for Patients With Metastatic Solid Tumors

• ClinicalTrials.gov Identifier: NCT02215928
• Recruitment Status: Recruiting
• First Posted: August 13, 2014
• Last Update Posted: November 22, 2023
• Sponsor: Stanford University
• Information provided by (Responsible Party): Stanford University

Tracking Information

• First Submitted Date: August 11, 2014
• First Posted Date: August 13, 2014
• Last Update Posted Date: November 22, 2023
• Actual Study Start Date: July 28, 2014
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 11, 2014)

Feasibility, measured as the proportion of patients with at least one actionable alteration [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 11, 2014)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Genomic Profiling in Recommending Treatment for Patients With Metastatic Solid Tumors
• Official Title: Tumor Genomic Profiling: A Personalized Medicine Approach
• 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 Type: Observational
• Study Design: Observational Model: Other; Time Perspective: Other
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

liquid biopsy

• Sampling Method: Non-Probability Sample
• Study Population: adult oncology clinic at the Stanford Cancer Institute
• Condition: Unspecified Adult Solid Tumor, Protocol Specific

Intervention

• Genetic: mutation analysis
  Correlative studies
• Other: cytology specimen collection procedure
  Correlative studies
  Other Name: cytologic sampling
• Other: laboratory biomarker analysis
  Correlative studies

Study Groups/Cohorts

Ancillary-correlative (tumor genomic profiling)

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.

Interventions:

• Genetic: mutation analysis
• Other: cytology specimen collection procedure
• Other: laboratory biomarker analysis

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 11, 2014): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2024
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Meredith Mills; 650-724-5223; bluett@stanford.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02215928
• Other Study ID Numbers: IRB-29525; NCI-2014-01662 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); VAR0114 ( Other Identifier: OnCore )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Stanford University
• Original Responsible Party: Same as current
• Current Study Sponsor: Stanford University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: James Ford; Stanford University Hospitals and Clinics

• PRS Account: Stanford University
• Verification Date: November 2023