Clinical Trials /

TIGER-2: A Phase 2, Open-label, Multicenter, Safety and Efficacy Study of Oral CO-1686 as 2nd Line EGFR-directed TKI in Patients With Mutant EGFR Non-small Cell Lung Cancer (NSCLC)

NCT02147990

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: TIGER-2: A Phase 2, Open-label, Multicenter, Safety and Efficacy Study of Oral CO-1686 as 2nd Line EGFR-directed TKI in Patients With Mutant EGFR Non-small Cell Lung Cancer (NSCLC)
  • Official Title: TIGER-2: A Phase 2, Open-label, Multicenter, Safety and Efficacy Study of Oral CO-1686 as 2nd Line EGFR-directed TKI in Patients With Mutant EGFR Non-small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: CO-1686-019 (TIGER-2)
  • NCT ID: NCT02147990

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
RociletinibCO-1686Rociletinib Mono-Therapy

Purpose

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.

Detailed Description

      This is a Phase 2, single arm, open-label, dual cohort, multicenter study evaluating the
      safety and efficacy of rociletinib administered orally to patients with previously treated
      mutant EGFR NSCLC.

      Patients will be enrolled into 2 cohorts. Cohort A will enroll approximately 125 eligible
      patients who are centrally confirmed T790M-positive. Cohort B will be a continuation of the
      study and will enroll up to approximately 100 eligible patients who will be either centrally
      confirmed T790M-positive or T790M-negative.

      All patients (for Cohort A and B) should have experienced disease progression while on
      treatment with the first single-agent EGFR-directed TKI (EGFR-TKI) for advanced/metastatic
      NSCLC. One line of chemotherapy prior to the EGFR-TKI treatment is permissible.

      The study (Cohorts A and B) will consist of a screening phase to establish study eligibility
      and document baseline measurements, an open-label treatment phase, in which the patient will
      receive rociletinib to ascertain safety and efficacy until disease progression as defined by
      RECIST Version 1.1, clinical tumor progression, or unacceptable toxicity as assessed by the
      investigator. For patients with clinical progression, radiographic assessment should be
      performed to document evidence of radiographic progression.
    

Trial Arms

NameTypeDescriptionInterventions
Rociletinib Mono-TherapyExperimental
  • Rociletinib

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response rate (ORR) according to RECIST Version 1.1 as determined by independent radiology review (IRR).
Time Frame:Every 8 weeks until disease progression, up to approximately 24 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Duration of Response (DR), Disease Control Rate (DCR) and Progression Free Survival (PFS) according to RECIST Version 1.1 as determined by IRR
Time Frame:Every 8 weeks until disease progression, up to approximately 24 months
Safety Issue:
Description:
Measure:Objective Response Rate (ORR), Duration of Response (DR), Progression Free Survival (PFS), Disease Control Rate (DCR) as determined by Investigator Assessment
Time Frame:Every 8 weeks until disease progression, up to approximately 24 months
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:Every 4-8 weeks until date of death, up to approximately 60 months
Safety Issue:
Description:
Measure:Change from baseline in patient reported outcomes using EORTC QLQ C30, EORTC Quality of Life Questionnaire Lung Cancer module (EORTC QLQ LC13), and the Dermatology Life Quality Index (DLQI)
Time Frame:Every 8-12 weeks until disease progression, up to approximately 24 months
Safety Issue:
Description:
Measure:Treatment emergent adverse events (AEs), laboratory abnormalities and ECG abnormalities
Time Frame:Every 4 weeks until treatment discontinuation, up to approximately 24 months
Safety Issue:
Description:
Measure:Plasma PK parameters for rociletinib based on sparse sampling
Time Frame:Every 4 weeks for approximately 6 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Clovis Oncology, Inc.

Trial 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

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