Next Generation Sequence Target-Directed Therapy in Treating Patients With Cancer

A Prospective Randomized Trial Comparing the Effectiveness of Physician Discretion Guided Therapy Versus Physician Discretion Guided Plus Next-Generation Sequence Directed Therapy

This randomized clinical trial studies how well next generation sequence target-directed therapy works in treating patients with cancer. Next generation sequencing is a test that screens for mutations to cancer related genes. Target-directed therapy is a type of treatment that uses drugs or other substances to identify and attack specific types of cancer cells that may have less harm to normal cells. Next generation sequencing may help identify these specific types of cancer cells.

Study Overview

• Status: Completed
• Conditions: Malignant Neoplasm
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: cytology specimen collection procedure; Procedure: therapeutic procedure; Drug: targeted therapy

Detailed Description

PRIMARY OBJECTIVES:

I. Overall (composite) response rate (ORR).

SECONDARY OBJECTIVES:

I. 4-month progression free survival (PFS). II. Mutation rate. III. Adverse event rate/severity. IV. Overall survival.

TERTIARY OBJECTIVES:

I. Targeted agent rate. II. Available protocol rate. III. Protocol enrollment rate. IV. Disease site influence.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients undergo collection of tissue and blood samples for analysis via next generation sequencing. Patients receive standard of care therapy based on the discretion of the treating physician.

ARM B: Patients undergo collection of tissue and blood samples for analysis via next generation sequencing. Based on the results of the next generation sequencing, patients receive target-directed therapy.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed cancer
• Patients must have evaluable disease; measureable disease is not required; however, if measurable disease is present, it is defined as at least one lesion that can be accurately measured in at least one dimension in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) criteria version (v.) 1.1; furthermore, if only evaluable disease is present, a relevant tumor marker (per investigator discretion) must be >= 2 times upper limit of normal (ULN) at baseline, and can be used as a response indicator

• Patients must be considered good candidates for a phase 1 trial and the treating physician must intend to enroll the patient on a phase 1 clinical protocol, if possible; patients are not required to have progressed on their last line of therapy prior to enrollment

  • Other clinical trials are also acceptable; for example, an applicable phase 2 or phase 3 trial may exist for which the patient would be eligible and for which available information (inclusive of next generation sequencing [NGS]) would be relevant to such enrollment; regardless, the pertinent point is that it is the intent of the physician to use NGS data, to the degree possible, to select appropriate therapy, when selecting patients for this trial
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Absolute neutrophil count > 1,000/mcL
• Platelets > 80,000/mcL
• Total bilirubin =< 1.5 times ULN and stable X 1 month
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) (serum glutamic oxaloacetic transaminase [SGOT]/serum glutamate pyruvate transaminase [SGPT]) < 3 times ULN (if liver metastasis is present then =< 5 X ULN)
• Serum creatinine =< 1.5 X ULN and stable X 1 month OR creatinine clearance >= 60 Ml/min/1.73 m^2
• Estimated life expectancy of >= 3 months
• Ability to understand and willingness to sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization

Exclusion Criteria:

• Patients with more than one type of active malignancy; an active malignancy is defined as one that is being treated with therapeutic intent and for which survival may be impacted, within 3 years of enrollment
• Patients with known active brain metastases; patients with a history of treated brain metastasis are eligible if the patient is off systemic steroids and there are no clinical indications of central nervous system (CNS) progression for a least 1 month; patients with glioblastoma multiforme are eligible if the above criteria are otherwise met; note: many clinical trials do not allow enrollment of such patients; if the physician, in good conscience, feels that applicable protocols for their patient do exist, enrollment onto this trial is acceptable, assuming other eligibility criteria are met
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Known human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy
• Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A (standard of care therapy); Patients undergo collection of tissue and blood samples for analysis via next generation sequencing. Patients receive standard of care therapy based on the discretion of the treating physician.	Other: laboratory biomarker analysis; Correlative studies; Other: cytology specimen collection procedure; Undergo collection of tissue and blood samples; Other Names: cytologic sampling; Procedure: therapeutic procedure; Receive standard of care therapy; Other Names: Therapy; Therapeutic Interventions; Therapeutic Method; Therapeutic Technique; TX
Experimental: Arm B (target-directed therapy); Patients undergo collection of tissue and blood samples for analysis via next generation sequencing. Based on the results of the next generation sequencing, patients receive target-directed therapy.	Other: laboratory biomarker analysis; Correlative studies; Other: cytology specimen collection procedure; Undergo collection of tissue and blood samples; Other Names: cytologic sampling; Drug: targeted therapy; Receive target-directed therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall (composite) response rate	The overall (composite) response rate will be defined by tumor response rate according to RECIST 1.1 or by tumor marker response for patients without measurable disease defined by RECIST 1.1. Tumor marker response will be quantified as a 50% reduction in the marker of interest, when compared to baseline, without any radiographic evidence of progressive disease.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	The percentage of patients progression free and alive will be estimated using the method of Kaplan and Meier. PFS in control will be compared to those in the experimental arm using log-rank tests.	Time from randomization to time of progression or death, whichever occurs first, assessed at 4 months
Mutation rate	Mutation rate, defined as the percentage of patients with >= 1 mutation identified will be estimated using the method of Pearson and Clopper as binomial proportions. 95% confidence intervals will be provided for these proportions.	Up to 2 years
Actionable mutation rate	The percentage of patients with "actionable" mutation rate will be estimated using the method of Pearson and Clopper as binomial proportions. 95% confidence intervals will be provided for these proportions.	Up to 2 years
Incidence of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0	The rate of adverse events will be estimated using the method of Pearson and Clopper as binomial proportions. 95% confidence intervals will be provided for these proportions. Adverse events will be tabulated according to severity.	Up to 2 years
Median overall survival	OS will be estimated using the method of Kaplan and Meier. OS in control will be compared to those in the experimental arm using log-rank tests.	Up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Targeted agent rate	The targeted agent rate will be estimated as the fraction of patients in arm B receiving target-directed therapy. 95% confidence intervals will be determined.	Up to 2 years
Available protocol rate	The available protocol rate will be estimated as the fraction of mutations for which a local protocol offers a potential therapeutic. 95% confidence intervals will be determined.	Up to 2 years
Protocol enrollment rate	The protocol enrollment rate will be estimated as the fraction of patients in any ongoing trial who participate in this one.	Up to 2 years
Disease site influence	Disease site influence will be characterized by the median OS and 4 month PFS for each disease site allocation.	Up to 2 years

Collaborators and Investigators

• Sponsor: Fox Chase Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Anthony Olszanski, Fox Chase Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2016
• Primary Completion (Actual): May 10, 2018
• Study Completion (Actual): May 10, 2018

Study Registration Dates

• First Submitted: May 6, 2014
• First Submitted That Met QC Criteria: May 6, 2014
• First Posted (Estimate): May 7, 2014

Study Record Updates

• Last Update Posted (Actual): February 4, 2021
• Last Update Submitted That Met QC Criteria: February 3, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CGI-065 (Other Identifier: Fox Chase Cancer Center); P30CA006927 (U.S. NIH Grant/Contract); NCI-2014-00716 (Registry Identifier: CTRP (Clinical Trial Reporting Program))