Clinical trial NCT02132884: 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
Overall status: TERMINATED
Phase: NA
Conditions: 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
Lead sponsor: Fox Chase Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-05-07
Enrollment: 1
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression Free Survival
timeFrame: Time from start of second line treatment to time of progression or death, whichever occurs first, assessed at 3 months
Secondary outcomes:
measure: Response Rate Defined by RECIST 1.1
timeFrame: Up to 2 years
measure: Proportion of Arm B Patients Whose Second Line Therapy is Changed as a Result of Physician Access to CancerCode-50 Results
timeFrame: Up to 2 years
Other outcomes:
measure: Concordance of Variants (Arm B)
timeFrame: Up to 2 years
measure: Incidence of Non-protocol Testing (Arm A)
timeFrame: Up to 2 years
measure: Response Rate Defined by RECIST 1.1 (Arm A)
timeFrame: Up to 2 years
measure: Progression Free Survival (Arm A)
timeFrame: Time from start of second line treatment to time of progression or death, whichever occurs first, assessed up to 2 year
Locations:
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
Study officials:
affiliation: Fox Chase Cancer Center
name: Hossein Borghaei
role: PRINCIPAL_INVESTIGATOR
References: