Clinical Trials /

Phase 1/2 Study of the Safety and Efficacy of Rociletinib in Combination With Trametinib in Patients With mEGFR-positive Advanced or Metastatic Non-small Cell Lung Cancer

NCT02580708

Description:

The purpose of this study is to evaluate the safety and anti-tumor effect of rociletinib when administered in combination with trametinib.

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

Terminated

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

A Phase 1/2 Study of the Safety and Efficacy of <span class="go-doc-concept go-doc-intervention">Rociletinib</span> When Administered in Combination With <span class="go-doc-concept go-doc-intervention">Trametinib</span> in Patients With Activating <span class="go-doc-concept go-doc-alteration">EGFR Mutation</span>-positive Advanced or Metastatic Non-<span class="go-doc-concept go-doc-disease">small Cell Lung Cancer </span>(<span class="go-doc-concept go-doc-disease">NSCLC</span>)

Title

  • Brief Title: A Phase 1/2 Study of the Safety and Efficacy of Rociletinib When Administered in Combination With Trametinib in Patients With Activating EGFR Mutation-positive Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)
  • Official Title: A Phase 1/2 Study of the Safety and Efficacy of Rociletinib When Administered in Combination With Trametinib in Patients With Activating EGFR Mutation-positive Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)
  • Clinical Trial IDs

    NCT ID: NCT02580708

    ORG ID: CO-1686-033

    Trial Conditions

    Non-small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Rociletinib CO-1686 Rociletinib and Trametinib
    Trametinib Mekinist Rociletinib and Trametinib

    Trial Purpose

    The purpose of this study is to evaluate the safety and anti-tumor effect of rociletinib
    when administered in combination with trametinib.

    Detailed Description

    This is a Phase 1/2, open-label, non randomized, multicenter study evaluating the safety and
    efficacy of rociletinib administered in combination with trametinib.

    This study will be conducted in 2 phases:

    Phase 1: This will be the dose escalation phase of the study. Phase 1 will determine the MAD
    or MTD and RP2D of the combination of rociletinib and trametinib, and evaluate its safety
    and tolerability and PK profile in EGFRm NSCLC patients who have failed at least one prior
    EGFR TKI.

    Phase 2: This will be the dose expansion phase. Phase 2 will evaluate the preliminary
    efficacy and pharmacodynamics of the combination of rociletinib and trametinib at the RP2D
    in two subsets of EGFRm NSCLC patients.

    Trial Arms

    Name Type Description Interventions
    Rociletinib and Trametinib Experimental Rociletinib, Trametinib

    Eligibility Criteria

    Inclusion Criteria:

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

    - Histologically or cytologically confirmed metastatic or unresectable locally advanced
    NSCLC with EGFR activating mutation (excluding exon 20 insertion); measurable disease
    per RECIST 1.1

    - Prior treatment with an EGFR TKI; in Phase 2, prior treatment with a T790M-directed
    EGFR TKI for patients in Group B. Previous chemotherapy is allowed; in Phase 2,
    immediate prior therapy must be EGFR TKI

    - Patient willingness to undergo tumor biopsy at baseline and on treatment (optional
    for Phase 1; mandatory for Phase 2)

    - Eastern Cooperative Oncology Group (ECOG) performance status 0-1; life expectancy at
    least 3 months

    - Adequate hematological and biological function; LVEF 50%

    Exclusion Criteria:

    - Documented evidence in tumor of exon 20 insertion, small cell transformation, or MET
    amplification

    - Leptomeningeal carcinomatosis or other untreated or symptomatic CNS metastases
    (asymptomatic CNS metastases allowed if clinically stable without requirement for
    steroids within 2 weeks)

    - Known preexisting interstitial lung disease or pneumonitis

    - Concurrent use of QT-prolonging medication

    - Uncontrolled diabetes (HA1C > 10%) despite optional therapy

    - Cardiac abnormalities:

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

    - Inability to measure QT interval on ECG

    - Personal or family history of long QT syndrome

    - Implantable pacemaker or implantable cardioverter defibrillator

    - Resting bradycardia < 55 beats/min

    - Inability to swallow oral study treatment or any gastrointestinal disease or
    condition that would preclude adequate absorption of study treatment

    - Presence of serious or unstable concomitant systemic disorder incompatible with the
    clinical study (eg, substance abuse; uncontrolled intercurrent illness including
    active infection; arterial thrombosis; unstable respiratory, hepatic, renal or
    cardiac disease; and other active malignancy)

    - Pregnant or breastfeeding females and male or female patients who refuse to use
    adequate contraception during the study and for 16 weeks after the last dose of study
    treatment

    - Any contraindication, allergy, or hypersensitivity to rociletinib, trametinib, or
    excipients

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence of treatment-emergent adverse events

    Objective Response Rate (ORR)

    Cmax of rociletinib and trametinib at steady state

    Tmax of rociletinib and trametinib at steady state

    AUC of rociletinib and trametinib at steady state

    Cmin of rociletinib and trametinib at steady state

    t1/2 of rociletinib at steady state

    Secondary Outcome Measures

    Duration of Response (DR) According to RECIST Version 1.1

    Disease Control Rate (DCR) According to RECIST Version 1.1

    Progression Free Survival (PFS) According to RECIST Version 1.1

    Overall Survival (OS)

    Longitudinal changes in blood based biomarkers (i.e. mutations in EGFR) in ctDNA

    Cmax of rociletinib metabolites at steady state

    Tmax of rociletinib metabolites at steady state

    AUC of rociletinib metabolites at steady state

    Cmin of rociletinib metabolites at steady state

    Trial Keywords