Clinical Trials /

Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options

NCT02650401

Description:

This is an open-label, Phase 1/2 multicenter dose escalation study in pediatric patients with relapsed or refractory extracranial solid tumors (Phase 1), with additional expansion cohorts (Phase 2) in patients with primary brain tumors harboring NTRK1/2/3 or ROS1 gene fusions, and extracranial solid tumors harboring NTRK1/2/3 or ROS1 gene fusions.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: A Phase 1/2, Open-Label, Dose-Escalation and Expansion 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

Clinical Trial IDs

  • ORG STUDY ID: RXDX-101-03
  • SECONDARY ID: CO40778
  • NCT ID: NCT02650401

Conditions

  • Solid Tumors
  • CNS Tumors

Interventions

DrugSynonymsArms
EntrectinibRXDX-101Extracranial solid tumors harboring NTRK1/2/3,

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Extracranial solid tumors harboring NTRK1/2/3,Active ComparatorROS1, ALK non-gene fusion molecular alterations Oral entrectinib (RXDX-101)
  • Entrectinib
CNS tumors harboring- NTRK1/2/3, ROS1, ALKActive Comparatormolecular alterations, including gene fusions Oral entrectinib (RXDX-101)
  • Entrectinib
NeuroblastomaActive ComparatorOral entrectinib (RXDX-101)
  • Entrectinib
Non-neuroblastoma, extracranial solid tumorsActive Comparatorharboring - NTRK1/2/3, ROS1, ALK gene fusions Oral entrectinib (RXDX-101)
  • Entrectinib
Any patient unable to swallow capsulesActive Comparatorwho otherwise meet all other eligibility criteria Oral entrectinib (RXDX-101)
  • Entrectinib
Expansion: CNS tumors harboring- NTRK1/2/3, ROS1, ALKActive Comparatormolecular alterations, including gene fusions Oral entrectinib (RXDX-101)
  • Entrectinib
Expansion: Extracranial solid tumors harboring NTRK1/2/3Active ComparatorROS1, ALK non-gene fusion molecular alterations Oral entrectinib (RXDX-101)
  • Entrectinib

Eligibility Criteria

        Inclusion Criteria:

          1. Ability to swallow capsules unless enrolled in Part E

          2. Body surface area (BSA): Subjects must have a body surface area ≥ 0.45 m2 at the time
             of the study enrollment, unless enrolled in Part E

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

          4. Tumor type:

               -  Part A: Relapsed or refractory extracranial solid tumors and (Phase 1b expansion)
                  relapsed or refractory extracranial solid tumors with molecular alterations,
                  non-gene fusions;

               -  Part B: Relapsed or refractory primary CNS tumors with molecular alterations,
                  including gene fusions, documented by a CLIA-approved lab prior to enrollment;

               -  Part C: Relapsed or refractory neuroblastoma;

               -  Part D: Relapsed or refractory non-neuroblastoma, extracranial solid tumors with
                  NTRK1/2/3, ROS1, or ALK gene fusions documented by a CLIA-approved lab prior to
                  enrollment;

               -  Part E: Any patient unable to swallow capsules who otherwise meet all other
                  eligibility criteria for Part A (expansion) B, C or D

          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 from birth to age < 22 years, unless enrolled in Part E

          8. Performance status: Lansky or Karnofsky score ≥ 60% and minimum life expectancy of at
             least 4 weeks

          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. Prior treatment with approved or investigational TRK, ROS1, or ALK inhibitors

          6. Patients with NB with bone marrow space-only disease

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

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

          9. 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.
      
Maximum Eligible Age:22 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD)
Time Frame:Approximately 6 months
Safety Issue:
Description:Assessed by National Cancer Institute Common Terminology for Adverse Events Criteria (NCI CTCAE v4.03)

Secondary Outcome Measures

Measure:Safety and Tolerability - AE, ECG and Labs assessed by NCI CTCAE v4.03
Time Frame:Approximately 24 months
Safety Issue:
Description:AE, ECG and Labs assessed by NCI CTCAE v4.03
Measure:Maximum observed plasma drug concentration (Cmax)
Time Frame:Approximately 24 months
Safety Issue:
Description:Assessed by plasma concentrations obtained Day 1 (Cycles 1 and 2)
Measure:Time to Cmax, by inspection (Tmax)
Time Frame:Approximately 24 months
Safety Issue:
Description:Assessed by plasma concentrations obtained Day 1 (Cycles 1 and 2)
Measure:Css
Time Frame:Approximately 24 months
Safety Issue:
Description:Assessed by plasma concentrations obtained Day 1 (Cycles 1 and 2)
Measure:Terminal half life (t½)
Time Frame:Approximately 24 months
Safety Issue:
Description:Assessed by plasma concentrations obtained Day 1 (Cycles 1 and 2)
Measure:Area under the drug concentration by time curve (AUC)
Time Frame:Approximately 24 months
Safety Issue:
Description:Assessed by plasma concentrations obtained Day 1 (Cycles 1 and 2)
Measure:Progression-free Survival (PFS)
Time Frame:Approximately 24 months
Safety Issue:
Description:Defined as time from the date of study enrollment to the first occurrence of objective disease progression or date of death due to any cause, whichever occurs first
Measure:Overall Survival (OS)
Time Frame:Approximately 24 months
Safety Issue:
Description:Assessed by RECIST v1.1

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

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
  • Sarcoma
  • Ewing sarcoma
  • Glial tumors
  • Salivary Gland Cancer (MASC)
  • Papillary thyroid cancer
  • Medulloblastoma
  • Wilms tumor (anaplastic)

Last Updated