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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Fox Chase Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fox Chase Cancer Center
ClinicalTrials.gov Identifier:
NCT02132884
First received: May 6, 2014
Last updated: NA
Last verified: May 2014
History: No changes posted
  Purpose

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.


Condition Intervention
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
Other: cytology specimen collection procedure
Procedure: therapeutic procedure
Drug: targeted therapy
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: CancerCodeTM Informed, Molecularly Targeted Therapies in Non-small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Fox Chase Cancer Center:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: Time from start of second line treatment to time of progression or death, whichever occurs first, assessed at 3 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Concordance of variants (Arm B) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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.

  • Incidence of non-protocol testing (Arm A) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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.

  • Response rate defined by RECIST 1.1 (Arm A) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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.

  • Progression free survival (Arm A) [ Time Frame: Time from start of second line treatment to time of progression or death, whichever occurs first, assessed up to 2 year ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 110
Study Start Date: April 2014
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A (standard of care treatment)
Patients receive standard of care treatment based on the discretion of the treating physician.
Procedure: therapeutic procedure
Receive standard of care treatment
Other Names:
  • Therapeutic Interventions
  • Therapeutic Method
  • Therapeutic Technique
  • Therapy
  • TX
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm B (genetic sequencing and targeted therapy)
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.
Other: cytology specimen collection procedure
Undergo collection of tissue and blood samples
Other Name: cytologic sampling
Drug: targeted therapy
Receive specific targeted therapy
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02132884

Locations
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Hossein Borghaei    215-214-4297    hossein.borghaei@fccc.edu   
Principal Investigator: Hossein Borghaei         
Sponsors and Collaborators
Fox Chase Cancer Center
Investigators
Principal Investigator: Hossein Borghaei Fox Chase Cancer Center
  More Information

No publications provided

Responsible Party: Fox Chase Cancer Center
ClinicalTrials.gov Identifier: NCT02132884     History of Changes
Other Study ID Numbers: CGI-068, NCI-2014-00717, CGI-068, P30CA006927
Study First Received: May 6, 2014
Last Updated: May 6, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Pericardial Effusion
Pleural Effusion
Pleural Effusion, Malignant
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Heart Diseases
Cardiovascular Diseases
Pleural Diseases
Pleural Neoplasms

ClinicalTrials.gov processed this record on July 29, 2014