Clinical Trials /

Study of Oral RXDX-101 in Adult Patients With Locally Advanced or Metastatic Cancer Targeting NTRK1, NTRK2, NTRK3, ROS1, or ALK Molecular Alterations.

NCT02097810

Description:

Entrectinib (RXDX-101) is an orally available inhibitor of the tyrosine kinases TrkA (coded by the gene NTRK1), TrkB (coded by the gene NTRK2), TrkC (coded by the gene NTRK3), ROS1 (coded by the gene ROS1), and ALK (coded by the gene ALK). Molecular alterations to one or more of these targets are present in several different tumor types, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), prostate cancer, papillary thyroid cancer, pancreatic cancer, and neuroblastoma. Patients with locally advanced or metastatic cancer with a detectable molecular alteration in targets of interest may be eligible for enrollment. Phase 1 will assess safety and tolerability of entrectinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and efficacy will be assessed in the dose expansion portion of the study.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

A Phase 1/2a Study of Oral <span class="go-doc-concept go-doc-intervention">RXDX-101</span> in Adult Patients With Locally Advanced or Metastatic Cancer; Study Targeting <span class="go-doc-concept go-doc-biomarker">ALK</span>, <span class="go-doc-concept go-doc-biomarker">ROS1</span>, or TRKA/B/C

Title

  • Brief Title: A Phase 1/2a Study of Oral RXDX-101 in Adult Patients With Locally Advanced or Metastatic Cancer; Study Targeting ALK, ROS1, or TRKA/B/C
  • Official Title: A Phase 1/2a, Multicenter, Open-Label Study of Oral RXDX-101 in Adult Patients With Locally Advanced or Metastatic Cancer Confirmed to be Positive for TrkA, TrkB, TrkC, ROS1, or ALK Molecular Alterations
  • Clinical Trial IDs

    NCT ID: NCT02097810

    ORG ID: RXDX-101-01

    Trial Conditions

    Locally Advanced Solid Tumors

    Metastatic Solid Tumors

    Trial Interventions

    Drug Synonyms Arms
    Entrectinib TrkA/TrkB/TrkC/ROS1/ALK inhibitor Entrectinib (RXDX-101)

    Trial Purpose

    Entrectinib (previously known as RXDX-101) is an orally available inhibitor of the tyrosine
    kinases TrkA, TrkB, TrkC, ROS1, and ALK. Molecular alterations to one or more of these
    targets are present in several different tumor types, including non-small cell lung cancer
    (NSCLC), colorectal cancer (CRC), prostate cancer, papillary thyroid cancer, pancreatic
    cancer, and neuroblastoma. Patients with locally advanced or metastatic cancer with a
    detectable molecular alteration in targets of interest may be eligible for enrollment.

    Phase 1 will assess safety and tolerability of entrectinib via standard dose escalation
    scheme and determine the recommended Phase 2 dose.

    Phase 2 will assess treatment efficacy and safety of entrectinib.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Entrectinib (RXDX-101) Experimental Oral entrectinib (RXDX-101) Entrectinib

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically or cytologically confirmed diagnosis of locally advanced or metastatic
    solid tumors that have a TrkA, TrkB, TrkC, ROS1, or ALK molecular alteration.

    - Measurable disease according to RECIST version 1.1.

    - Prior cancer therapy is allowed, including crizotinib and investigational drugs. At
    the time of treatment start, at least 2-4 weeks must have elapsed after prior
    cytotoxic chemotherapy (at least 6 weeks for nitrosureas, mitomycin C and liposomal
    doxorubicin). In the absence of toxicity, 7 days must have elapsed since completion
    of prior non-cytotoxic cancer therapy.

    - Prior radiotherapy is allowed if >14 days have elapsed since end of treatment,
    provided that no more than 25% of bone marrow reserve has been irradiated.

    - Patients with controlled asymptomatic central nervous system involvement are allowed
    in absence of therapy with anticonvulsants.

    - Patients who have received brain irradiation must have completed whole brain
    radiotherapy and gamma knife at least 4 weeks prior to enrollment.

    - Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer
    therapy to National Cancer Institute Common Terminology Criteria for Adverse Events
    (NCI CTCAE) Version 4.03 Grade less than or equal to 1.

    - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2.

    - Adult patients age 18 years or older.

    - Life expectancy of at least 3 months.

    Exclusion Criteria:

    - Current participation in another therapeutic clinical trial.

    - Known symptomatic brain metastases or leptomeningeal involvement as assessed by MRI
    or contrast CT scan examination.

    - History of previous cancer, except squamous cell or basal-cell carcinoma of the skin,
    or any in situ carcinoma that has been completely resected, requiring therapy within
    the previous 3 years.

    - Incomplete recovery from any surgery prior to treatment.

    - Any of the following in the past 6 months: myocardial infarction, unstable angina,
    coronary/peripheral artery bypass graft, symptomatic congestive heart failure,
    cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein
    thrombosis.

    - History of prolonged QTc interval (e.g., repeated demonstration of a QTc interval >
    450 milliseconds).

    - History of additional risk factors for torsade de pointes (e.g., heart failure,
    family history of long QT syndrome).

    - Use of concomitant medications that increase or possibly increase the risk to prolong
    the QTc interval and/or induce torsades de pointes ventricular arrhythmia.

    - Known active infections (bacterial, fungal, viral including HIV positivity).

    - Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut
    syndrome) or other malabsorption syndromes that would impact on drug absorption.

    - Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase
    inhibitor-induced pneumonitis.

    - Other severe acute or chronic medical or psychiatric condition or laboratory
    abnormality that may increase the risk associated with study participation or study
    drug administration or may interfere with the interpretation of study results and, in
    the judgment of the Investigator, would make the patient inappropriate for entry into
    this study or could compromise protocol objectives in the opinion of the Investigator
    and/or the Sponsor.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Phase 1: Dose-Limiting Toxicity (DLT)

    Phase 1: Maximum Tolerated Dose (MTD)

    Phase 1: Recommended Phase 2 Dose (RP2D)

    Phase 2a: Objective response

    Secondary Outcome Measures

    Plasma concentrations of entrectinib

    Progression-Free Survival (PFS)

    Overall Survival (OS)

    Disease Control

    Duration of Response

    Trial Keywords