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Study Of Entrectinib (Rxdx-101) in Children and Adolescents With No Curative First-Line Treatment Option, Recurrent or Refractory Solid Tumors And Primary Cns Tumors, With or Without Trk, Ros1, or Alk Fusions

NCT02650401

Description:

This is a 5-part, open-label, Phase 1/2 multicenter, dose escalation study in pediatric patients with relapsed refractory solid tumors; 2) primary CNS tumors; 3) neuroblastoma; 4) non-neuroblastoma, extracranial solid tumors with NTRK1/2/3, ROS1 or ALK gene rearrangements; and 5) patients who are otherwise eligible but unable to swallow capsules. The study is designed to explore the safety, maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D), pharmacokinetics, and antitumor activity of entrectinib.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Study of RXDX-101 in Children With Recurrent or Refractory Solid Tumors and Primary <span class="go-doc-concept go-doc-disease">CNS</span> Tumors

Title

  • Brief Title: Study of RXDX-101 in Children With Recurrent or Refractory Solid Tumors and Primary CNS Tumors
  • Official Title: A Phase 1/1b, Open-Label, Dose-Escalation and Expansion Study of Entrectinib (RXDX 101) in Children and Adolescents With Recurrent or Refractory Solid Tumors and Primary CNS Tumors
  • Clinical Trial IDs

    NCT ID: NCT02650401

    ORG ID: RXDX-101-03

    Trial Conditions

    Solid Tumors

    CNS Tumors

    Neuroblastoma

    Trial Interventions

    Drug Synonyms Arms
    Entrectinib RXDX-101 Solid tumors, CNS tumors, Neuroblastoma, Solid tumors-NTRK1/2/3, ROS1, ALK gene rearranged

    Trial Purpose

    This is a 4-part, open-label, Phase 1/1b, dose escalation study in pediatric patients with
    relapsed refractory solid tumors; 2) primary CNS tumors; 3) neuroblastoma; and 4)
    non-neuroblastoma, extracranial solid tumors with NTRK1/2/3, ROS1 or ALK gene
    rearrangements. The study is designed to explore the safety, maximum tolerated dose (MTD) or
    recommended Phase 2 dose (RP2D), pharmacokinetics, and antitumor activity of entrectinib.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Solid tumors Active Comparator Oral entrectinib (RXDX-101) Entrectinib
    CNS tumors Active Comparator Oral entrectinib (RXDX-101) Entrectinib
    Neuroblastoma Active Comparator Oral entrectinib (RXDX-101) Entrectinib
    Solid tumors-NTRK1/2/3, ROS1, ALK gene rearranged Active Comparator Oral entrectinib (RXDX-101) Entrectinib

    Eligibility Criteria

    Inclusion Criteria:

    1. Ability to swallow capsules

    2. Body surface area (BSA): Subjects must have a body surface area 0.45 m2 at the time
    of the study enrollment

    3. Disease status: Subjects must have measurable or evaluable disease, by RECIST v1.1
    Curie Scale Criteria

    4. Tumor type:

    Part A: Relapsed or refractory extracranial solid tumors Part B: Relapsed or
    refractory primary CNS tumors Part C: Relapsed or refractory neuroblastoma Part D:
    Relapsed or refractory non-neuroblastoma, extracranial solid tumors with NTRK1/2/3,
    ROS1, or ALK gene rearrangements documented by a CLIA-approved lab prior to
    enrollment

    5. Histologic/molecular diagnosis of malignancy at diagnosis or the time of relapse

    6. Archival tumor tissue from diagnosis or, preferably, at relapse

    7. Age: Male or female age 2 years and < 22 years

    8. Performance status: Lansky or Karnofsky score 60%

    9. Patient's cancer must have relapsed after or failed to respond to frontline curative
    therapy or there must not be other potentially curative treatment options available

    10. Adequate organ and neurologic function

    11. Females of child bearing potential must have a negative serum pregnancy test within
    14 days prior to entrectinib dosing

    Exclusion Criteria:

    1. Receiving other experimental therapy

    2. Known congenital long QT syndrome

    3. Known active infections

    4. Receiving Enzyme Inducing Antiepileptic Drugs (EIAEDs) within 14 days of first dose.

    5. Incomplete recovery from acute effects of any surgery prior to treatment.

    6. Active gastrointestinal disease or other malabsorption syndromes that would impact
    drug absorption.

    7. Other severe acute or chronic medical or psychiatric condition or lab abnormality
    that may increase the risk associated with study participation, drug administration
    or may interfere with the interpretation of study results.

    Minimum Eligible Age: 2 Years

    Maximum Eligible Age: 22 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Maximum Tolerated Dose (MTD)

    Recommended Phase 2 Dose (RP2D)

    Secondary Outcome Measures

    Safety and Tolerability - AE, ECG and Labs assessed by NCI CTCAE v4.03

    Maximum observed plasma drug concentration (Cmax)

    Time to Cmax, by inspection (Tmax)

    Css

    Terminal half life (t)

    Area under the drug concentration by time curve (AUC)

    Objective Response Rate (ORR)

    Progression-free Survival (PFS)

    Trial Keywords

    TRK

    Tyrosine kinase

    NTRK

    NTRK1

    NTRK2

    NTRK3

    ROS1

    ALK

    Pediatric

    Relapsed

    Refractory

    Solid Tumor

    Metastatic Cancer

    Gene rearrangement

    Neuroblastoma

    Infantile fibrosarcoma

    Secretory breast cancer

    Congenital mesoblastic nephroma

    Pontine glioma

    Brain tumors

    CNS tumors