Multicenter Study of Rociletinib Administered to Patients With Previously Treated Mutant EGFR Non-small Cell Lung Cancer
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Rociletinib
Intervention description: Rociletinib will be administered to patients orally
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 318.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: cancer; metastatic; locally advanced; lung; non-small cell lung cancer; NSCLC; epidermal growth factor receptor; EGFR; T790M; CO-1686; unresectable; recurrent; EGFR-directed therapy; irreversible EGFR inhibitor; TIGER; Rociletinib

Summary:

      The purpose of this study is to evaluate the safety and anti-tumor effect of rociletinib. The
      trial is open-ended, which means patients will continue to take rociletinib until the study
      doctor determines it is no longer beneficial for them.
    

Eligibility criteria:

        Inclusion Criteria

          -  Histologically or cytologically confirmed metastatic or unresectable locally advanced
             NSCLC

          -  Documented evidence of a tumor with 1 or more EGFR mutations excluding exon 20
             insertion

          -  Disease progression confirmed by radiologic assessment while receiving treatment with
             the first single agent EGFR-TKI

          -  EGFR TKI treatment discontinued less than or equal to 30 days prior to planned
             initiation of rociletinib

          -  The washout period for an EGFR inhibitor is a minimum of 3 days

          -  No intervening treatment between cessation of single agent EGFR TKI and planned
             initiation of rociletinib

          -  Previous treatment with less than or equal to 1 prior chemotherapy (excluding prior
             neo-adjuvant or adjuvant chemotherapy or chemoradiotherapy with curative intent)

          -  Any toxicity related to prior EGFR inhibitor treatment must have resolved to Grade 1
             or less

          -  Central laboratory confirmation of the presence of the T790M mutation in tumor tissue
             in Cohort A and the presence or absence of the T790M mutation in tumor tissue in
             Cohort B. Centrally indeterminate, unknown or invalid specimens are not acceptable.
             Biopsy material obtained from either primary or metastatic tumor tissue and sent to
             the central laboratory must be within 60 prior to dosing study drug but following
             disease progression on the first EGFR TKI

          -  Measurable disease according to RECIST Version 1.1

          -  Life expectancy of at least 3 months

          -  ECOG performance status of 0 to 1

          -  Minimum Age 18 years (in certain territories, the minimum age requirement may be
             higher eg age 20 years in Japan and Taiwan)

          -  Adequate hematological and biological function, confirmed by defined laboratory values

          -  Written consent on an IRB/IEC-approved Informed Consent Form (ICF) prior to any study
             specific evaluation

        Exclusion Criteria

          -  Documented evidence of an exon 20 insertion activating mutation in the EGFR gene

          -  Active second malignancy i.e. patient known to have potentially fatal cancer present
             for which he/she may be (but not necessarily) currently receiving treatment

          -  Patients with a history of malignancy that has been completely treated, with no
             evidence of that cancer currently, are permitted to enrol in the trial provided all
             chemotherapy was completed greater than 6 months prior and/or bone marrow transplant
             greater than 2 years prior

          -  Known pre-existing interstitial lung disease

          -  Cohort A only: Patients with leptomeningeal carcinomatosis are excluded. Other central
             nervous system (CNS) metastases are only permitted if treated, asymptomatic, and
             stable (not requiring steroid for at least 4 weeks prior to the start of study
             treatment). Cohort B only: Patients with CNS metastases or leptomeningeal
             carcinomatosis are excluded.

          -  Treatment with prohibited medications less than or equal to 14 days prior to treatment
             with rociletinib

          -  Patients who are currently receiving treatment with any medications that have the
             potential to prolong the QT interval and the treatment cannot be either discontinued
             or switched to a different medication before starting rociletinib

          -  Prior treatment with rociletinib, or other drugs that target T790M positive mutant
             EGFR with sparing of wild type EGFR

          -  Any of the following cardiac abnormalities or history

          -  Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's
             method (QTCF) greater than 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 less than 55 beats/min

          -  Non-study related surgical procedures less than or equal to 7 days prior to
             administration of rociletinib. In all cases, the patient must be sufficiently
             recovered and stable before treatment administration

          -  Females who are pregnant or breastfeeding

          -  Refusal to use adequate contraception for fertile patients (females and males) while
             on treatment and for 12 weeks after the last dose of rociletinib

          -  Presence of any serious or unstable concomitant systemic disorder incompatible with
             the clinical study

          -  Any other reason the investigator considers the patient should not participate in the
             study