Comprehensive Gene Sequencing in Guiding Treatment Recommendations Patients With Metastatic or Recurrent Solid Tumors

Decision Impact Analysis of Foundation Medicine's Next Generation Sequencing Test in Advanced Solid Tumor Malignancies

This pilot clinical trial studies comprehensive gene sequencing in guiding treatment recommendations in patients with metastatic or recurrent solid tumors. Studying samples of blood and tissue from patients with cancer in the laboratory may improve the ability to plan treatment.

Study Overview

• Status: Completed
• Conditions: Stage IV Breast Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer
• Intervention / Treatment: Other: cytology specimen collection procedure; Other: laboratory biomarker analysis

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the feasibility and logistics associated with a clinical trial utilizing the Foundation Medicine Incorporated (FMI) test in an academic therapeutic setting.

II. To determine the proportion of patients who will receive a cancer-related therapy based on the results provided by the FMI test.

SECONDARY OBJECTIVES:

I. To explore and report estimates of progression free survival (PFS) of the regimen administered after the FMI test results are revealed and the PFS of the most recent regimen administered before the FMI test results were received.

II. To determine the feasibility of performing Next Generation Sequencing (NGS) on metastatic tumor tissue.

III. To determine the feasibility of administering cancer-related drugs that are proposed by the results of NGS that are not Food and Drug Administration (FDA)-approved for a patient's specific cancer diagnosis.

IV. To collect and report the molecular alterations discovered by NGS of advanced breast and colorectal cancer.

V. To determine in an exploratory manner the concordance of the genomic alterations detected by the FMI test in circulating tumor cells (CTCs) to the genomic alterations detected by FMI test in tumor tissues collected from the same patient.

OUTLINE:

PART I: Within 10 weeks of beginning a treatment regimen, tumor tissue samples and CTCs from patients are collected for NGS and FMI testing, respectively. Patients remain on current line of therapy until a change in treatment is warranted. The physician's treatment recommendation is documented prior to the release of the FMI results.

PART II: Physicians are furnished with FMI test results when patients become eligible for a change in therapy and new treatment recommendations are documented. Treatment is dependent on preferences of the physician, patient, and/or results of the FMI test.

After completion of study, patients are followed up for at least 18 months.

• Study Type: Observational
• Enrollment (Actual): 150

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with recurrent or metastatic a solid tumor cancer.

Description

Inclusion Criteria:

• Are able to understand and provide written informed consent (most recent patient informed consent form) prior to initiation of any study-specific procedures
• Patients are diagnosed with recurrent or metastatic a solid tumor cancer; the first patients to be enrolled will have a diagnosis of breast cancer (Cohort 1) or colorectal cancer (Cohort 2)
• Patients may enter this study at any line of therapy
• Patients must have a tumor sample available for NGS testing
• Patients are within 10 weeks of starting their current line of therapy and enrolled before their 1st computed tomography (CT) scan
• Have an expected survival of >= 3 months, as estimated by the treating oncologist
• Have an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2

Exclusion Criteria:

• Are pregnant or nursing women
• Are unable to comply with requirements of the study
• Have a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Observational (NGS, FMI testing); PART I: Within 10 weeks of beginning a treatment regimen, tumor tissue samples, Blood Collection and CTCs(Circulating tumor cell)from patients are collected for NGS and FMI testing, respectively. Patients remain on current line of therapy until a change in treatment is warranted. The physician's treatment recommendation is documented prior to the release of the FMI results. PART II: Physicians are furnished with FMI test results when patients become eligible for a change in therapy and new treatment recommendations are documented. Treatment is dependent on preferences of the physician, patient, and/or results of the FMI test.

Other: cytology specimen collection procedure; Undergo collection of CTCs for NGS and FMI testing, respectively.The most recent tumor sample collected from the patient with enough tissue to perform NGS testing will be selected. Tumor from a metastatic or recurrent cancer lesion is preferred but not required. Tumor collection is for standard of care purposes and thus not detailed in this protocol.For each tissue specimen, a representative H&E stained section will be evaluated by a qualified pathologist to confirm the histopathological diagnosis of cancer and to make a quantitative estimate of the proportion of the specimen that is tumor-related cells and the proportion that is non-tumor cells.; Other Names: cytologic sampling; Other: laboratory biomarker analysis; 2 tubes of 7.5 mL blood samples each will be collected at time tumor tissue is sent to FMI and sent to Cynvenio Biosystems, Inc for CTC isolation and analysis. Patient CTCs will be recovered using Cynvenio CTC flow cell technology (Cynvenio Biosystems, Inc.) and enumerated using a combination of CD45, DAPI and cytokeratin staining.1 DNA will be isolated from CTCs and amplified using Φ-29 whole genome amplification (GE Healthcare). Sequencing to be performed by FoundationOne™ protocol.; Other Names: blood samples; Correlative studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of NGS on metastatic solid tumor tissue, in terms of number of patients screened, FMI test attempted, FMI test successful, and FMI tests results released to physicians	Summary tables will be generated.	Up to 18 months
Feasibility of NGS result-based non-FDA-approved treatment plan, measured by reasons for ability or inability to receive an anti-cancer agent	Summary tables will be generated.	Up to 18 months
Availability of recommended experimental regimens via clinical trials		Up to 18 months
Proportion of patients who have one recommended therapy	The proportion of patients who have one recommended therapy recommended will be assessed and compared with the proportion who have multiple options recommended. Summarized, and estimates derived along with corresponding 95% confidence intervals.	Up to 18 months
Proportion of patients who have multiple options recommended	The proportion of patients who have one recommended therapy recommended will be assessed and compared with the proportion who have multiple options recommended. Summarized, and estimates derived along with corresponding 95% confidence intervals.	Up to 18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Presence of any oncogene or tumor suppressor gene mutations or amplifications identified by NGS on tumor tissue in each cohort	Up to 18 months

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center
• Collaborators: Foundation Medicine

Publications and helpful links

General Publications

• Adams EJ, Asad S, Reinbolt R, Collier KA, Abdel-Rasoul M, Gillespie S, Chen JL, Cherian MA, Noonan AM, Sardesai S, VanDeusen J, Wesolowski R, Williams N, Shapiro CL, Macrae ER, Pilarski R, Toland AE, Senter L, Ramaswamy B, Lee CN, Lustberg MB, Stover DG. Metastatic breast cancer patient perceptions of somatic tumor genomic testing. BMC Cancer. 2020 May 6;20(1):389. doi: 10.1186/s12885-020-06905-2.

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2013
• Primary Completion (Actual): June 10, 2021
• Study Completion (Actual): June 28, 2021

Study Registration Dates

• First Submitted: November 13, 2013
• First Submitted That Met QC Criteria: November 13, 2013
• First Posted (Estimate): November 19, 2013

Study Record Updates

• Last Update Posted (Actual): October 28, 2021
• Last Update Submitted That Met QC Criteria: October 21, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Solid Tumor Malignancies
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Breast Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Breast Neoplasms; Recurrence; Rectal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: OSU-12067; NCI-2013-00872 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No