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TIGER-3: Open Label, Multicenter Study of Rociletinib (CO-1686) Mono Therapy Versus Single-agent Cytotoxic Chemotherapy in Patients With Mutant EGFR NSCLC Who Have Failed at Least One Previous EGFR-Directed TKI and Platinum-doublet Chemotherapy

NCT02322281

Description:

The purpose of this study is to compare the anti-tumor efficacy of oral single-agent rociletinib, as measured by investigator assessment of the PFS, with that of single-agent cytotoxic chemotherapy in patients with EGFR-mutated, advanced/metastatic NSCLC after failure of at least 1 previous EGFR-directed TKI and at least 1 line of platinum-containing doublet chemotherapy.

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

Terminated

Phase:

Phase 3

Trial Eligibility

Document

TIGER-3: Open Label, Multicenter Study of <span class="go-doc-concept go-doc-intervention">Rociletinib</span> (CO-1686) Mono Therapy Versus Single-agent Cytotoxic <span class="go-doc-concept go-doc-intervention">Chemotherapy</span> in Patients With <span class="go-doc-concept go-doc-keyword">Mutant</span> <span class="go-doc-concept go-doc-biomarker">EGFR</span> NSCLC Who Have Failed at Least One Previous <span class="go-doc-concept go-doc-biomarker">EGFR</span>-Directed <span class="go-doc-concept go-doc-intervention">TKI</span> and <span class="go-doc-concept go-doc-intervention">Platinum</span>-doublet <span class="go-doc-concept go-doc-intervention">Chemotherapy</span>

Title

  • Brief Title: TIGER-3: Open Label, Multicenter Study of Rociletinib (CO-1686) Mono Therapy Versus Single-agent Cytotoxic Chemotherapy in Patients With Mutant EGFR NSCLC Who Have Failed at Least One Previous EGFR-Directed TKI and Platinum-doublet Chemotherapy
  • Official Title: TIGER-3: A Phase 3, Open-label, Multicenter, Randomized Study of Oral Rociletinib (CO-1686) Monotherapy Versus Single-agent Cytotoxic Chemotherapy in Patients With Mutant EGFR Non-small Cell Lung Cancer (NSCLC) After Failure of at Least 1 Previous EGFR-directed Tyrosine Kinase Inhibitor (TKI) and Platinum-doublet Chemotherapy
  • Clinical Trial IDs

    NCT ID: NCT02322281

    ORG ID: CO-1686-020 (TIGER-3)

    Trial Conditions

    Non-small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Rociletinib CO-1686 Rociletinib Monotherapy
    Pemetrexed or gemcitabine or paclitaxel or docetaxel Pemetrexed or gemcitabine or paclitaxel or docetaxel

    Trial Purpose

    The purpose of this study is to compare the anti-tumor efficacy of oral single-agent
    rociletinib, as measured by investigator assessment of the PFS, with that of single-agent
    cytotoxic chemotherapy in patients with EGFR-mutated, advanced/metastatic NSCLC after
    failure of at least 1 previous EGFR-directed TKI and at least 1 line of platinum-containing
    doublet chemotherapy.

    Detailed Description

    This is a Phase 3, randomized, open-label, multicenter study evaluating the safety and
    efficacy of oral rociletinib compared with that of single-agent cytotoxic chemotherapy, in
    patients with previously treated mutant EGFR NSCLC. Eligible patients are those with mutant
    EGFR NSCLC previously treated with at least 1 EGFR inhibitor and at least 1 line of
    platinum-containing chemotherapy doublet for advanced/metastatic NSCLC.

    After providing informed consent to participate and screening to confirm eligibility,
    patients will be randomized 1:1 to receive rociletinib or single-agent cytotoxic
    chemotherapy (investigator choice of pemetrexed, gemcitabine, docetaxel, or paclitaxel;
    choice of chemotherapy agent must be specified before randomization).

    Trial Arms

    Name Type Description Interventions
    Rociletinib Monotherapy Experimental Daily oral rociletinib at 625 mg BID with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Treatment with rociletinib is continuous and each cycle will comprise of 21 days. Rociletinib
    Pemetrexed or gemcitabine or paclitaxel or docetaxel Active Comparator Pemetrexed 500 mg/m2 pemetrexed given intravenously on Day 1 of each 21-day cycle. Gemcitabine 1250 mg/m2 gemcitabine given intravenously on Day 1 and 8 of each 21-day cycle. Docetaxel 75 mg/m2 docetaxel (60 mg/m2 in Asian patients) given intravenously on Day 1 of each 21-day cycle. or 35 mg/m2 docetaxel given intravenously on a weekly basis as part of a continuous 21-day cycle; i.e. dosing will be on Days 1, 8, and 15 of each 21-day cycle. Paclitaxel 80 mg/m2 paclitaxel given intravenously on a weekly basis as part of a continuous 21-day cycle; i.e. dosing will be on Days 1, 8, and 15 of each 21-day cycle. Pemetrexed or gemcitabine or paclitaxel or docetaxel

    Eligibility Criteria

    Inclusion Criteria:

    All patients must meet all of the following inclusion criteria:

    1. Histologically or cytologically confirmed metastatic or unresectable locally advanced
    NSCLC with radiological progression on the most recent therapy received

    2. Documented evidence of a tumor with 1 or more EGFR activating mutations excluding
    exon 20 insertion

    3. Disease progression confirmed by radiological assessment while receiving treatment
    with single agent EGFR-TKI (e.g., erlotinib, gefitinib, afatinib, or dacomitinib).

    4. Multiple lines of prior treatment are permitted and there is no specified order of
    treatment, but in the course of their treatment history, patients must have received
    and have radiologically documented disease progression following:

    At least 1 line of prior treatment with a single-agent EGFR TKI (e.g., erlotinib,
    gefitinib, afatinib, or dacomitinib)

    If EGFR-TKI is a component of the most recent treatment line, the washout period for
    the EGFR-TKI is a minimum of 3 days before the start of rociletinib treatment

    AND

    A platinum-containing doublet chemotherapy (either progressed during therapy or
    completed at least 4 cycles without progression with subsequent progression after a
    treatment-free interval or after a maintenance treatment).

    If cytotoxic chemotherapy is a component of the most recent treatment line, treatment
    with chemotherapy should have been completed at least 14 days prior to start of study
    treatment. When an EGFR-TKI is given in combination with platinum-containing doublet
    chemotherapy, treatment with the EGFR-TKI may continue until at least 3 days before
    start of treatment.

    5. Have undergone a biopsy of either primary or metastatic tumor tissue within 60 days
    prior to start of treatment and have tissue available to send to sponsor laboratory
    or are able to undergo a biopsy during screening and provide tissue to sponsor
    laboratory

    6. Measureable disease according to RECIST Version 1.1

    7. Life expectancy of at least 3 months

    8. ECOG performance status of 0 to 1

    9. Age 18 years (in certain territories, the minimum age requirement may be higher
    e.g., age 20 years in Japan and Taiwan, age 21 years in Singapore)

    10. Patients should have recovered to National Cancer Institute (NCI) Common Terminology
    Criteria for Adverse Events (CTCAE) Grade 1 from any significant
    chemotherapy-related toxicities

    11. Adequate hematological and biological function

    12. Written consent on an Institutional Review Board (IRB)/Independent Ethics Committee
    (IEC)-approved ICF before any study specific evaluation

    Exclusion Criteria:

    Any of the following criteria will exclude patients from study participation:

    1. Any other malignancy associated with a high mortality risk within the next 5 years
    and for which the patients 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 enroll in the trial provided all
    chemotherapy was completed > 6 months prior and/or bone marrow transplant > 2 years
    prior

    2. Known pre-existing interstitial lung disease

    3. Tumor small cell transformation by local assessment, irrespective of presence of
    T790M+ component

    4. Patients with leptomeningeal carcinomatosis are excluded. Other central nervous
    system (CNS) metastases are only permitted if treated, asymptomatic, and stable (not
    requiring steroids for at least 2 weeks prior to randomization and the patient is
    neurologically stable i.e. free from new symptoms of brain metastases).

    5. Patients who are currently receiving treatment with any medications that have the
    potential to prolong the QT interval and that treatment cannot be either discontinued
    or switched to a different medication (known to have no effect on QT) before starting
    protocol-specified treatment (see http://crediblemeds.org/ for a list of
    QT-prolonging medications)

    6. Prior treatment with rociletinib, or other drugs that target T790M+ mutant EGFR with
    sparing of WT-EGFR including but not limited to AZD9291, HM61713, and TAS-121

    7. Any contraindications for therapy with pemetrexed, paclitaxel, gemcitabine or
    docetaxel unless a contraindication with respect to one of these drugs will not
    affect the use of any of the others as a comparator to rociletinib

    8. Any of the following cardiac abnormalities or history:

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

    2. Inability to measure QT interval on ECG

    3. Personal or family history of long QT syndrome

    4. Implantable pacemaker or implantable cardioverter defibrillator

    5. Resting bradycardia < 55 beats/min

    9. Non-study related surgical procedures 7 days prior to randomization. In all cases,
    the patient must be sufficiently recovered and stable before treatment administration

    10. Females who are pregnant or breastfeeding

    11. Refusal to use adequate contraception for fertile patients (females and males) while
    on treatment and for 6 months after the last dose of study treatment (rociletinib and
    chemotherapy irrespective of single cytotoxic agent used)

    12. Presence of any serious or unstable concomitant systemic disorder incompatible with
    the clinical study (e.g., substance abuse, uncontrolled intercurrent illness
    including uncontrolled diabetes, active infection, arterial thrombosis, and
    symptomatic pulmonary embolism)

    13. 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

    PFS according to RECIST Version 1.1 as determined by investigator assessment

    Secondary Outcome Measures

    ORR, DR, and DCR according to RECIST Version 1.1 as determined by investigator assessment

    OS

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

    Plasma PK parameters for rociletinib based on sparse sampling

    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