Clinical Trials /

TIGER-1: Safety and Efficacy Study of Rociletinib (CO-1686) or Erlotinib in Patients With EGFR-mutant/Metastatic NSCLC Who Have Not Had Any Previous EGFR Directed Therapy

NCT02186301

Description:

The purpose of this study is to compare the safety and anti-tumor effect of rociletinib with erlotinib in patients whose tumors have specific EGFR mutations and who have not previously received any treatment for advanced/metastatic EGFR mutated NSCLC. This study is a 'Randomized' Study. This means that upon entering the study, patients will be randomly assigned to be dosed with either rociletinib twice a day or erlotinib once a day. Patients will continue to take either rociletinib or erlotinib until it is no longer beneficial.

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

Terminated

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

TIGER-1: Safety and Efficacy Study of <span class="go-doc-concept go-doc-intervention">Rociletinib</span> (CO-1686) or <span class="go-doc-concept go-doc-intervention">Erlotinib</span> in Patients With <span class="go-doc-concept go-doc-biomarker">EGFR</span> <span class="go-doc-concept go-doc-keyword">Mutant</span> NSCLC Who Have Not Had Any Previous <span class="go-doc-concept go-doc-biomarker">EGFR</span> Directed Therapy

Title

  • Brief Title: TIGER-1: Safety and Efficacy Study of Rociletinib (CO-1686) or Erlotinib in Patients With EGFR Mutant NSCLC Who Have Not Had Any Previous EGFR Directed Therapy
  • Official Title: TIGER 1: A Randomized, Open-Label, Phase 2 Study of CO-1686 or Erlotinib as First-Line Treatment of Patients With EGFR-Mutant Advanced NSCLC
  • Clinical Trial IDs

    NCT ID: NCT02186301

    ORG ID: CO-1686-022 (TIGER-1)

    Trial Conditions

    Non-Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Rociletinib Mono-Therapy Rociletinib Mono-Therapy
    Erlotinib Mono-Therapy Erlotinib Mono-Therapy

    Trial Purpose

    The purpose of this study is to compare the safety and anti-tumor effect of rociletinib with
    erlotinib, another EGFR TKI drug, in patients whose tumors have specific EGFR mutations and
    who have not previously received any EGFR TKI therapy. This study is a 'Randomized' Study.
    This means that upon entering the study, patients will be randomly assigned to be dosed with
    either rociletinib twice a day or erlotinib once a day. Patients will continue to take
    either rociletinib or erlotinib until it is no longer beneficial. For patients assigned to
    erlotinib, there will be the possibility of subsequent treatment with rociletinib once
    erlotinib treatment is stopped because erlotinib is no longer effective treating cancer and
    if the patient is found to have the T790M mutation.

    Detailed Description

    This is a randomized, open-label, Phase 2 study of rociletinib versus erlotinib as a
    first-line treatment for patients with EGFR-mutant advanced NSCLC. Patients will be
    randomized 1:1 to erlotinib or rociletinib. The study will consist of a Screening phase to
    establish study eligibility (including tumor genotype) and document baseline measurements,
    an open-label treatment phase, in which patients will receive either rociletinib BID or
    erlotinib QD to ascertain safety and efficacy until protocol-defined disease progression,
    and a follow-up phase, to monitor survival status and subsequent NCSLC cancer therapy.
    Patients initially randomized to erlotinib may be eligible to participate in an optional
    crossover phase to receive rociletinib if they demonstrate the T790M resistance mutation
    after radiographic progression on erlotinib treatment among other eligibility requirements.
    Patients eligible for this study must have EGFR mutated NSCLC who have not been treated with
    an EGFR directed therapy.Treatment with rociletinib or erlotinib is continuous. Each 28 day
    period of treatment will represent one cycle, with dosing initiated on Cycle 1 Day 1 (C1
    D1).

    Trial Arms

    Name Type Description Interventions
    Erlotinib Mono-Therapy Active Comparator Erlotinib Mono-Therapy
    Rociletinib Mono-Therapy Experimental Rociletinib Mono-Therapy

    Eligibility Criteria

    Inclusion Criteria:

    1. Histologically or cytologically confirmed metastatic or unresectable locally advanced
    recurrent NSCLC

    2. Documented evidence of a tumor with one or more activating EGFR mutations excluding
    exon 20 insertion

    3. Have undergone a biopsy or surgical resection of either primary or metastatic tumor
    tissue within 60 days of planned randomization and have tissue available to send to
    sponsor lab or are able to undergo a biopsy during Screening and provide tissue to
    sponsor lab

    4. No prior EGFR-directed therapy

    5. Measureable disease according to RECIST Version 1.1

    6. Life expectancy of at least 3 months

    7. ECOG performance status of 0 to 1

    8. Minimum age 18 years (in certain territories, the minimum age requirement may be
    higher (e.g. 20 years in Japan and Taiwan)

    9. Adequate hematological and biological function, confirmed by defined laboratory
    values

    Exclusion Criteria:

    1. Documented evidence of an exon 20 insertion activating mutation in the EGFR gene

    2. Prior treatment with cytotoxic chemotherapy for advanced NSCLC; neoadjuvant/adjuvant
    chemotherapy is permitted if at least 6 months has elapsed between the end of
    chemotherapy and randomization

    3. 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

    4. Patients with a history of malignancy that has been completely treated, with no
    evidence of that cancer currently, are permitted to enroll in the trial provided all
    chemotherapy was completed > 6 months prior and/or bone marrow transplant > 2 years
    prior to first day of study treatment

    5. Known pre-existing interstitial lung disease

    6. Brain metastases

    7. Treatment with prohibited medications less than or equal to14 days prior to first day
    of study treatment

    8. Patients who are currently receiving treatment with any medications that have the
    potential to prolong the QT interval if that treatment cannot be either discontinued
    or switched to a different medication prior to administration of study drug

    9. Prior treatment with EGFR TKIs, rociletinib or other drugs that target mutant EGFR

    10. Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's
    method (QTCF) > 450 ms

    11. Inability to measure QT interval on ECG

    12. Personal or family history of long QT syndrome

    13. Implantable pacemaker or implantable cardioverter defibrillator

    14. Resting bradycardia < 55 beats/min

    15. Non-study related surgical procedures less than or equal to 7 days prior to
    administration of study drug. In all cases, the patient must be sufficiently
    recovered and stable before treatment administration.

    16. Females who are pregnant or breastfeeding

    17. Refusal to use adequate contraception for fertile patients (females and males) for 12
    weeks after the last dose of rociletinib and 2 weeks after the last dose of erlotinib

    18. Presence of any serious or unstable concomitant systemic disorder incompatible with
    the clinical study

    19. Any other reason the investigator considers the patient should not participate in the
    study

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression Free Survival (PFS) according to RECIST Version 1.1 as determined by investigator review (invPFS)

    Secondary Outcome Measures

    Disease Control Rate (DCR) according to RECIST 1.1 as determined by investigator review

    invPFS in patients with baseline T790M mutations detected in tumor using local screening EGFR mutation assay

    Change from baseline in patient reported outcomes using the Dermatology Life Quality Index (DLQI) following treatment with CO-1686 versus erlotinib

    Treatment emergent adverse events (AEs), laboratory abnormalities and electrocardiogram (ECG) abnormalities

    Plasma PK parameters for rociletinib based on sparse sampling

    Overall Survival (OS)

    Objective Response Rate (ORR) according to RECIST 1.1 as determined by investigator review

    Duration of Response (DR) according to RECIST 1.1 as determined by investigator review

    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