Rociletinib Genomic Landscape in Non-small Cell Lung Cancer (NSCLC)
Primary Purpose
Carcinoma, Non-Small-Cell Lung, Non-Small Cell Lung Cancer, Nonsmall Cell Lung Cancer
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Rociletinib
Biopsy
Blood draw
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed metastatic stage IIIB/IV lung adenocarcinoma with known activating mutations in the EGFR TK domain (including exon 19 deletion and L858R)
- Prior EGFR TKI therapy with progression, and documented EGFR T790M mutation on tumor biopsy; however, this need not be only second line
- Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- At least 18 years of age.
- ECOG performance status ≤ 2
Normal bone marrow and organ function as defined below:
- Leukocytes ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcl
- Platelets ≥ 100,000/mcl
- Hemoglobin ≥ 9.0 g/dL
- INR ≤ 2.0
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Creatinine ≤ IULN OR creatinine clearance ≥ 45 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- Potassium within institutional limits (supplementation allowed)
- Magnesium within normal limits (supplementation allowed)
- Tumor tissue available and deemed adequate for genomic studies.
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Exclusion Criteria:
- A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
- Currently receiving any other investigational agents.
- Received therapeutic oral or IV antibiotics within 2 weeks prior to first day of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible.
- Symptomatic, untreated or unstable central nervous system or leptomeningeal metastases. (Patients with treated and stable brain metastases (confirmed by 2 scans at least 4 weeks apart), with no evidence of cavitation or hemorrhage in the brain lesion are eligible provided that they are asymptomatic and do not require corticosteroids.)
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to rociletinib or other agents used in the study.
- Currently receiving treatment with any medication that has the potential to prolong the QT interval and the treatment cannot be discontinued or switched to a different medication.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the previous 3 months, coronary angioplasty or stenting or bypass grafting within the past 6 months, cardiac ventricular arrhythmias requiring medication, any history of 2nd or 3rd degree atrioventricular conduction defects, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- History of interstitial lung disease.
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Class II to IV heart failure as defined by the New York Heart Association functional classification system. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF < 50% must be on a stable medial regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate, to be eligible.
Any of the following cardiac abnormalities or history:
- Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) > 450 msec
- Inability to measure QT interval on ECG
- Personal or family history of long QT syndrome
- Implantable pacemaker or implantable cardioverter defibrillator
- Resting bradycardia < 55 beats/min
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry.
- Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with rociletinib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
- Active hepatitis B virus (HBV) defined by positive hepatitis B surface antigen (HBsAg) test at screening. Patients with past or resolved HBV infection (defined by a negative HBsAg test and a positive anti-hepatitis B core antigen (anti-HBc) antibody test) are eligible. HBV DNA must be obtained in these patients prior to first day of study treatment.
- Active hepatitis C virus (HCV). Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
- Active tuberculosis.
- Presence of active GI disease (including GI bleeding or ulceration) or other condition that could affect GI absorption) (e.g. malabsorption syndrome, history of biliary tract disease).
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm 1: Rociletinib
Arm Description
Rociletinib is an oral drug which will be administered on an outpatient basis at a dose of 500 mg twice per day during each 28-day cycle. After completion of cycle 1, patients who tolerate the 500 mg twice per day dose without significant adverse effect may increase dosing to 625 mg twice per day at the discretion of the investigator
Outcomes
Primary Outcome Measures
Somatic genetic changes in the tumor associated with disease progression
-The investigators plan to conduct exome and transcriptome sequencing of tumor before therapy with rociletinib and at the time of relapse. In addition, exome sequencing of peripheral blood DNA will be done (for germ line).
Secondary Outcome Measures
Overall response rate (ORR)
ORR: Percentage of patients experiencing complete response or partial response
Complete Response (CR): Disappearance of all target lesions and non-target lesions.
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Overall survival (OS)
Progression-free survival (PFS)
-PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Duration of treatment
Full Information
NCT ID
NCT02705339
First Posted
January 12, 2016
Last Updated
May 16, 2016
Sponsor
Washington University School of Medicine
Collaborators
Clovis Oncology, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02705339
Brief Title
Rociletinib Genomic Landscape in Non-small Cell Lung Cancer (NSCLC)
Official Title
Genomic Landscape of EGFR Mutant NSCLC Prior to Rociletinib and at the Time of Disease Progression Following Rociletinib
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Withdrawn
Why Stopped
Clovis Oncology discontinued rociletinib.
Study Start Date
May 2016 (undefined)
Primary Completion Date
November 2019 (Anticipated)
Study Completion Date
April 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
Clovis Oncology, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Though patients whose tumors harbor EGFR T790M mutation appear to benefit from rociletinib, there is a need to understand the molecular mechanisms that lead to primary and acquired resistance to rociletinib. The investigators propose to conduct a clinical trial of rociletinib of patients with EGFR-mutant NSCLC with activating EGFR mutations (including exon 19 deletion or L858R mutation), with or without EGFR T790M mutation. In these patients, pre-treatment and post-progression biopsy specimens will be subjected to genomic analysis to fully understand the clonal evolution and the molecular mechanisms underpinning treatment resistance.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Non-Small-Cell Lung, Non-Small Cell Lung Cancer, Nonsmall Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1: Rociletinib
Arm Type
Experimental
Arm Description
Rociletinib is an oral drug which will be administered on an outpatient basis at a dose of 500 mg twice per day during each 28-day cycle.
After completion of cycle 1, patients who tolerate the 500 mg twice per day dose without significant adverse effect may increase dosing to 625 mg twice per day at the discretion of the investigator
Intervention Type
Drug
Intervention Name(s)
Rociletinib
Other Intervention Name(s)
CO-1686
Intervention Type
Procedure
Intervention Name(s)
Biopsy
Intervention Description
Standard of care biopsies will be taken at diagnosis and at the time of disease progression
Intervention Type
Procedure
Intervention Name(s)
Blood draw
Intervention Description
-Approximately 4 teaspoons of blood will be drawn before treatment begins and at the time of disease progression to look at cell-free DNA
Primary Outcome Measure Information:
Title
Somatic genetic changes in the tumor associated with disease progression
Description
-The investigators plan to conduct exome and transcriptome sequencing of tumor before therapy with rociletinib and at the time of relapse. In addition, exome sequencing of peripheral blood DNA will be done (for germ line).
Time Frame
Until the time of disease progression (estimated median of 3 months)
Secondary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
ORR: Percentage of patients experiencing complete response or partial response
Complete Response (CR): Disappearance of all target lesions and non-target lesions.
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame
Until the time of disease progression (estimated median of 3 months)
Title
Overall survival (OS)
Time Frame
Until death (estimated median of 8 months)
Title
Progression-free survival (PFS)
Description
-PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Time Frame
Until the time of progression (estimated median of 3 months)
Title
Duration of treatment
Time Frame
Until the time of removal from study (estimated median of 3 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed metastatic stage IIIB/IV lung adenocarcinoma with known activating mutations in the EGFR TK domain (including exon 19 deletion and L858R)
Prior EGFR TKI therapy with progression, and documented EGFR T790M mutation on tumor biopsy; however, this need not be only second line
Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
At least 18 years of age.
ECOG performance status ≤ 2
Normal bone marrow and organ function as defined below:
Leukocytes ≥ 3,000/mcL
Absolute neutrophil count ≥ 1,500/mcl
Platelets ≥ 100,000/mcl
Hemoglobin ≥ 9.0 g/dL
INR ≤ 2.0
Total bilirubin ≤ 1.5 x IULN
AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
Creatinine ≤ IULN OR creatinine clearance ≥ 45 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
Potassium within institutional limits (supplementation allowed)
Magnesium within normal limits (supplementation allowed)
Tumor tissue available and deemed adequate for genomic studies.
Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Exclusion Criteria:
A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
Currently receiving any other investigational agents.
Received therapeutic oral or IV antibiotics within 2 weeks prior to first day of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible.
Symptomatic, untreated or unstable central nervous system or leptomeningeal metastases. (Patients with treated and stable brain metastases (confirmed by 2 scans at least 4 weeks apart), with no evidence of cavitation or hemorrhage in the brain lesion are eligible provided that they are asymptomatic and do not require corticosteroids.)
A history of allergic reactions attributed to compounds of similar chemical or biologic composition to rociletinib or other agents used in the study.
Currently receiving treatment with any medication that has the potential to prolong the QT interval and the treatment cannot be discontinued or switched to a different medication.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the previous 3 months, coronary angioplasty or stenting or bypass grafting within the past 6 months, cardiac ventricular arrhythmias requiring medication, any history of 2nd or 3rd degree atrioventricular conduction defects, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
History of interstitial lung disease.
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
Class II to IV heart failure as defined by the New York Heart Association functional classification system. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF < 50% must be on a stable medial regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate, to be eligible.
Any of the following cardiac abnormalities or history:
Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) > 450 msec
Inability to measure QT interval on ECG
Personal or family history of long QT syndrome
Implantable pacemaker or implantable cardioverter defibrillator
Resting bradycardia < 55 beats/min
Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry.
Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with rociletinib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
Active hepatitis B virus (HBV) defined by positive hepatitis B surface antigen (HBsAg) test at screening. Patients with past or resolved HBV infection (defined by a negative HBsAg test and a positive anti-hepatitis B core antigen (anti-HBc) antibody test) are eligible. HBV DNA must be obtained in these patients prior to first day of study treatment.
Active hepatitis C virus (HCV). Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
Active tuberculosis.
Presence of active GI disease (including GI bleeding or ulceration) or other condition that could affect GI absorption) (e.g. malabsorption syndrome, history of biliary tract disease).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Saiama Waqar, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
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Rociletinib Genomic Landscape in Non-small Cell Lung Cancer (NSCLC)
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