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Genetic Sequencing-Informed Targeted Therapy in Treating Patients With Stage IIIB-IV Non-small Cell Lung Cancer

Primary Purpose

Malignant Pericardial Effusion, Malignant Pleural Effusion, Recurrent Non-small Cell Lung Cancer

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
cytology specimen collection procedure
therapeutic procedure
targeted therapy
laboratory biomarker analysis
Sponsored by
Fox Chase Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Pericardial Effusion

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with cytologically or histologically confirmed non-small cell lung cancer (NSCLC) - locally advanced, stage IIIB OR stage IV or stage IVM1A (malignant pleural or pericardial effusion or pleural implants) OR recurrence after primary surgery or radiotherapy (refer to 2010 American Joint Committee on Cancer [AJCC] staging, 7th edition [Ed])
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST)-1.1 criteria; previous irradiated tumor is acceptable if there is at least a 20% increase in the size of the previously irradiated lesion
  • Patients must be suitable candidates for treatment with standard regimens; this includes having adequate hematologic parameters, liver function and renal function based on labs that are deemed acceptable for treatment by the investigators
  • Previous radiation allowed provided that 2 weeks has passed since radiation and/or the patient has recovered from the side effects
  • Availability of archival diagnostic tissue (paraffin tissue block, cytospin block from a fine needle aspirate, or unstained slides from resected tumor, core biopsy, or fine needle aspirate) is required
  • Able and willing to sign an informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization
  • Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must agree to use effective methods of contraception during active treatment and for the duration of the study

Exclusion Criteria:

  • Prior treatment with any investigational or targeted therapies
  • Patients with known activating mutations in the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma receptor tyrosine kinase (ALK) or c-ros oncogene 1, receptor tyrosine kinase (ROS-1) (this test [ROS-1] will be done only on select patients and at the discretion of treating physicians) translocation positive; the mutational status of all patients will be determined prior to study entry
  • Prior malignancy within the past 3 years other than complete resection of basal or squamous cell carcinoma of the skin, any in situ malignancy, or low-risk prostate cancer after curative therapy
  • Prior systemic therapy within 14 days of initiating protocol treatment
  • Symptomatic brain metastasis or asymptomatic brain metastasis that are 1 cm or greater in size; patients with asymptomatic sub-centimeter brain metastasis are eligible
  • Uncontrolled or unstable medical or psychiatric co-morbidities which would clearly limits patients participation
  • Current, recent (within 2 weeks of enrollment of this study), or planned participation in an experimental drug study
  • Unstable angina
  • Pregnant (positive serum pregnancy test) or breast feeding
  • History of any disease that could lead to impaired absorption of drugs
  • Inability to comply with study and/or follow-up procedures
  • Prior allogeneic bone marrow or organ

Sites / Locations

  • Fox Chase Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm A (standard of care treatment)

Arm B (genetic sequencing and targeted therapy)

Arm Description

Patients receive standard of care treatment based on the discretion of the treating physician.

Patients undergo collection of tissue and blood samples for analysis via sequencing. Upon disease progression following front-line treatment, patients receive specific targeted therapy based on the mutational status obtained during sequencing.

Outcomes

Primary Outcome Measures

Progression Free Survival
A chi-square test (one-sided; alpha = .1) will be used to assess the efficacy of treating patients with targeted agents based in the Cancer-Code-50 in the second line setting. For each patient "success" will be defined as being progression free for at least 3 months following initiation of second line therapy. Progression free survival times will be characterized separately by arm using the method of Kaplan and Meier.

Secondary Outcome Measures

Response Rate Defined by RECIST 1.1
The response rate (with 95% two-sided confidence intervals) will be computed separately by arm. One-sided chi-square or Fisher's exact tests (alpha = .1) will be used to evaluate differences in response rates between arms.
Proportion of Arm B Patients Whose Second Line Therapy is Changed as a Result of Physician Access to CancerCode-50 Results
To assess the effect of sequencing on clinical practice and decision making the proportion of Arm B patients whose second line therapy is changed as a result of physician access to CancerCode-50 results will be computed. This comparison will be based on information provided by the treating physician before being exposed to the sequencing results, and information obtained from a from post-treatment chart review.

Full Information

First Posted
May 6, 2014
Last Updated
August 21, 2019
Sponsor
Fox Chase Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02132884
Brief Title
Genetic Sequencing-Informed Targeted Therapy in Treating Patients With Stage IIIB-IV Non-small Cell Lung Cancer
Official Title
CancerCodeTM Informed, Molecularly Targeted Therapies in Non-small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Terminated
Why Stopped
Feasibility
Study Start Date
March 2015 (undefined)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
August 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fox Chase Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This randomized clinical trial studies how well genetic sequencing-informed targeted therapy works in treating patients with stage IIIB-IV non-small cell lung cancer. Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific types of tumor cells that may have less harm to normal cells. Genetic sequencing may help identify these specific types of tumor cells in patients with non-small cell lung cancer.
Detailed Description
PRIMARY OBJECTIVES: I. The three month progression free survival (PFS) of patients treated with targeted agents in the second line setting based on the tumor molecular signature as defined by CancerCode will be 40% vs 20% with standard cytotoxic chemotherapy. SECONDARY OBJECTIVES: I. Response rate (RR). II. Overall survival (OS). III. Proportion of Arm-B patients whose second line therapy is changed as a result of physician access to CancerCode-50 results. IV. Concordance of variants identified when sequencing is performed on samples from the same patient collected at baseline and follow-up time points. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: 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 sequencing. Upon disease progression following front-line treatment, patients receive specific targeted therapy based on the mutational status obtained during sequencing. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 1 year, and then annually thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Pericardial Effusion, Malignant Pleural Effusion, Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A (standard of care treatment)
Arm Type
Active Comparator
Arm Description
Patients receive standard of care treatment based on the discretion of the treating physician.
Arm Title
Arm B (genetic sequencing and targeted therapy)
Arm Type
Experimental
Arm Description
Patients undergo collection of tissue and blood samples for analysis via sequencing. Upon disease progression following front-line treatment, patients receive specific targeted therapy based on the mutational status obtained during sequencing.
Intervention Type
Other
Intervention Name(s)
cytology specimen collection procedure
Other Intervention Name(s)
cytologic sampling
Intervention Description
Undergo collection of tissue and blood samples
Intervention Type
Procedure
Intervention Name(s)
therapeutic procedure
Other Intervention Name(s)
Therapeutic Interventions, Therapeutic Method, Therapeutic Technique, Therapy, TX
Intervention Description
Receive standard of care treatment
Intervention Type
Drug
Intervention Name(s)
targeted therapy
Intervention Description
Receive specific targeted therapy
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Progression Free Survival
Description
A chi-square test (one-sided; alpha = .1) will be used to assess the efficacy of treating patients with targeted agents based in the Cancer-Code-50 in the second line setting. For each patient "success" will be defined as being progression free for at least 3 months following initiation of second line therapy. Progression free survival times will be characterized separately by arm using the method of Kaplan and Meier.
Time Frame
Time from start of second line treatment to time of progression or death, whichever occurs first, assessed at 3 months
Secondary Outcome Measure Information:
Title
Response Rate Defined by RECIST 1.1
Description
The response rate (with 95% two-sided confidence intervals) will be computed separately by arm. One-sided chi-square or Fisher's exact tests (alpha = .1) will be used to evaluate differences in response rates between arms.
Time Frame
Up to 2 years
Title
Proportion of Arm B Patients Whose Second Line Therapy is Changed as a Result of Physician Access to CancerCode-50 Results
Description
To assess the effect of sequencing on clinical practice and decision making the proportion of Arm B patients whose second line therapy is changed as a result of physician access to CancerCode-50 results will be computed. This comparison will be based on information provided by the treating physician before being exposed to the sequencing results, and information obtained from a from post-treatment chart review.
Time Frame
Up to 2 years
Other Pre-specified Outcome Measures:
Title
Concordance of Variants (Arm B)
Description
The concordance of variants identified when sequencing will be performed on samples from the same patient collected at baseline and follow-up time points will also be measured.
Time Frame
Up to 2 years
Title
Incidence of Non-protocol Testing (Arm A)
Description
The incidence of non-protocol testing of those patients in Arm A who undergo molecular testing (by any method) at the discretion of the treating physician will be estimated.
Time Frame
Up to 2 years
Title
Response Rate Defined by RECIST 1.1 (Arm A)
Description
The response rate of those patients in Arm A who undergo molecular testing (by any method) at the discretion of the treating physician will be estimated.
Time Frame
Up to 2 years
Title
Progression Free Survival (Arm A)
Description
The progression free survival of those patients in Arm A who undergo molecular testing (by any method) at the discretion of the treating physician will be estimated.
Time Frame
Time from start of second line treatment to time of progression or death, whichever occurs first, assessed up to 2 year

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with cytologically or histologically confirmed non-small cell lung cancer (NSCLC) - locally advanced, stage IIIB OR stage IV or stage IVM1A (malignant pleural or pericardial effusion or pleural implants) OR recurrence after primary surgery or radiotherapy (refer to 2010 American Joint Committee on Cancer [AJCC] staging, 7th edition [Ed]) Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST)-1.1 criteria; previous irradiated tumor is acceptable if there is at least a 20% increase in the size of the previously irradiated lesion Patients must be suitable candidates for treatment with standard regimens; this includes having adequate hematologic parameters, liver function and renal function based on labs that are deemed acceptable for treatment by the investigators Previous radiation allowed provided that 2 weeks has passed since radiation and/or the patient has recovered from the side effects Availability of archival diagnostic tissue (paraffin tissue block, cytospin block from a fine needle aspirate, or unstained slides from resected tumor, core biopsy, or fine needle aspirate) is required Able and willing to sign an informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must agree to use effective methods of contraception during active treatment and for the duration of the study Exclusion Criteria: Prior treatment with any investigational or targeted therapies Patients with known activating mutations in the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma receptor tyrosine kinase (ALK) or c-ros oncogene 1, receptor tyrosine kinase (ROS-1) (this test [ROS-1] will be done only on select patients and at the discretion of treating physicians) translocation positive; the mutational status of all patients will be determined prior to study entry Prior malignancy within the past 3 years other than complete resection of basal or squamous cell carcinoma of the skin, any in situ malignancy, or low-risk prostate cancer after curative therapy Prior systemic therapy within 14 days of initiating protocol treatment Symptomatic brain metastasis or asymptomatic brain metastasis that are 1 cm or greater in size; patients with asymptomatic sub-centimeter brain metastasis are eligible Uncontrolled or unstable medical or psychiatric co-morbidities which would clearly limits patients participation Current, recent (within 2 weeks of enrollment of this study), or planned participation in an experimental drug study Unstable angina Pregnant (positive serum pregnancy test) or breast feeding History of any disease that could lead to impaired absorption of drugs Inability to comply with study and/or follow-up procedures Prior allogeneic bone marrow or organ
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hossein Borghaei
Organizational Affiliation
Fox Chase Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Genetic Sequencing-Informed Targeted Therapy in Treating Patients With Stage IIIB-IV Non-small Cell Lung Cancer

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