Rociletinib Genomic Landscape in Non-small Cell Lung Cancer (NSCLC)

NCT02705339 | Withdrawn Phase 2

• 1 other identifier: 201604010
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Carcinoma, Non-Small-Cell Lung; Nonsmall Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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).

  Until the time of disease progression (estimated median of 3 months)

Secondary Outcomes (4)

• Overall response rate (ORR)

  Until the time of disease progression (estimated median of 3 months)

• Overall survival (OS)

  Until death (estimated median of 8 months)

• Progression-free survival (PFS)

  Until the time of progression (estimated median of 3 months)

• Duration of treatment

  Until the time of removal from study (estimated median of 3 months)

Study Arms (1)

Arm 1: Rociletinib

EXPERIMENTAL

* 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

Drug: Rociletinib; Procedure: Biopsy; Procedure: Blood draw

Interventions

Rociletinib DRUG

Also known as: CO-1686

Arm 1: Rociletinib

Biopsy PROCEDURE

Standard of care biopsies will be taken at diagnosis and at the time of disease progression

Arm 1: Rociletinib

Blood draw PROCEDURE

-Approximately 4 teaspoons of blood will be drawn before treatment begins and at the time of disease progression to look at cell-free DNA

Arm 1: Rociletinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Clovis Oncology, Inc.: collaborator

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

rociletinib; Biopsy; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Punctures

Study Officials

• Saiama Waqar, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2016
• First Posted: March 10, 2016
• Study Start: May 1, 2016
• Primary Completion: November 1, 2019
• Study Completion: April 1, 2020
• Last Updated: May 17, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share