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 (STARTRK-NG)

A Phase 1/2, Open-Label, Dose-Escalation And Expansion Study Of Entrectinib (Rxdx-101) In Pediatrics With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Tumors; CNS Tumors
• Intervention / Treatment: Drug: Entrectinib

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
• China
  • Beijing, China
    • Beijing Children's Hospital, Capital Medical University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200082
      • Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
• France
  • Lyon, France, 69373
    • Centre Leon Berard
  • Marseille, France, 13385
    • Hôpital de la Timone, Oncologie Pédiatrique
• Germany
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69120
      • Universitaetsklinikum Heidelberg
• Hong Kong
  • Hong Kong, Hong Kong, 00000
    • Hong Kong Children's Hospital
• Italy
  • Lombardy
    • Milan, Lombardy, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori
• Spain
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Nino Jesus
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital (Sutton)
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary
• United States
  • California
    • La Jolla, California, United States, 92093-0706
      • University of California San Diego
    • San Francisco, California, United States, 94158
      • UCSF Benioff Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Egleston Children's Hospital at Emory University Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University,St. Louis Children's Hospital
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science Uni
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Cancer and Hematology Center
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Disease status:

   • Phase 1 portion (closed): Participants must have measurable or evaluable disease, as defined by RECIST v1.1

   • Phase 2 portion:

     • Part B: Participants must have measurable or evaluable disease, as defined by RANO
     • Part C (closed): Participants must have measurable or evaluable disease, as defined by RECIST v1.1 ± Curie Scale
     • Part D: Participants must have measurable or evaluable disease, as defined by RECIST v1.1
     • Part E (closed): Participants must have measurable or evaluable disease, as defined by RECIST v1.1 ± Curie Scale or RANO

2. Tumor type:

   • Phase 1 portion:

     * Part A: Relapsed or refractory extracranial solid tumors

   • Phase 2 portion

     • Part B: Primary brain tumors with NTRK1/2/3 or ROS1 gene fusions; gene fusions are defined as those predicted to translate into a fusion protein with a functional TRKA/B/C or ROS1 kinase domain, without a concomitant second oncodriver as determined by a nucleic acid-based diagnostic testing method
     • Part D: Extracranial solid tumors (including NB) with NTRK1/2/3 or ROS1 gene fusions; gene fusions are defined as those predicted to translate into a fusion protein with a functional TRKA/B/C or ROS1 kinase domain, without a concomitant second oncodriver as determined by a nucleic acid-based diagnostic testing method
3. Histologic/molecular diagnosis of malignancy at diagnosis or the time of relapse
4. Archival tumor tissue from diagnosis or, preferably, at relapse
5. Performance status: Lansky or Karnofsky score ≥ 60% and minimum life expectancy of at least 4 weeks
6. Prior therapy: Participants must have a disease that is locally advanced, metastatic, or where surgical resection is likely to result in severe morbidity, and who have no satisfactory treatment options for solid tumors and primary CNS tumors that are neurotrophic tyrosine receptor kinase (NTRK) or ROS1 fusion-positive
7. Participants must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to enrollment
8. Adequate organ and neurologic function
9. Females of childbearing potential must have a negative serum pregnancy test during screening and be neither breastfeeding nor intending to become pregnant during study participation. Agreement to remain abstinent or use use combined contraceptive methods prior to study entry, for the duration of study participation and in the following 90 days after discontinuation of study treatment.
10. For male participants with a female partner of childbearing potential or a pregnant female partner: Agreement to remain abstinent or use a condom during the treatment period and for at least 3 months after the last dose of study drug

Exclusion Criteria:

1. Receiving other experimental therapy
2. Known congenital long QT syndrome
3. History of recent (3 months) symptomatic congestive heart failure or ejection fraction ≤50% at screening
4. Known active infections
5. Familial or personal history of congenital bone disorders, bone metabolism alterations or osteopenia
6. Receiving Enzyme Inducing Antiepileptic Drugs (EIAEDs) within 14 days of first dose.
7. Prior treatment with approved or investigational TRK or ROS1 inhibitors
8. Known hypersensitivity to entrectinib or any of the other excipients of the investigational medicinal product
9. Patients with NB with bone marrow space-only disease
10. Incomplete recovery from acute effects of any surgery prior to treatment.
11. Active gastrointestinal disease or other malabsorption syndromes that would impact drug absorption.
12. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Extracranial solid tumors harboring NTRK1/2/3,; Arm closed for further enrollment ROS1, ALK non-gene fusion molecular alterations Oral entrectinib (RXDX-101)	Drug: Entrectinib; TRKA/B/C, ROS1, and ALK inhibitor; Other Names: RXDX-101
Active Comparator: CNS tumors harboring- NTRK1/2/3, ROS1, ALK; Arm closed for further enrollment molecular alterations, including gene fusions Oral entrectinib (RXDX-101)	Drug: Entrectinib; TRKA/B/C, ROS1, and ALK inhibitor; Other Names: RXDX-101
Active Comparator: Neuroblastoma; Arm closed for further enrollment Oral entrectinib (RXDX-101)	Drug: Entrectinib; TRKA/B/C, ROS1, and ALK inhibitor; Other Names: RXDX-101
Active Comparator: Non-neuroblastoma, extracranial solid tumors; Arm closed for further enrollment harboring - NTRK1/2/3, ROS1, ALK gene fusions Oral entrectinib (RXDX-101)	Drug: Entrectinib; TRKA/B/C, ROS1, and ALK inhibitor; Other Names: RXDX-101
Active Comparator: Any participant unable to swallow capsules; Arm closed for further enrollment Any participant who otherwise meet all other eligibility criteria Oral entrectinib (RXDX-101)	Drug: Entrectinib; TRKA/B/C, ROS1, and ALK inhibitor; Other Names: RXDX-101
Active Comparator: Expansion: CNS tumors harboring NTRK1/2/3, ROS1; gene fusions Oral entrectinib (RXDX-101)	Drug: Entrectinib; TRKA/B/C, ROS1, and ALK inhibitor; Other Names: RXDX-101
Active Comparator: Expansion: Extracranial solid tumors harboring NTRK1/2/3, ROS1; NTRK 1,2,3 and ROS1 fusions Oral entrectinib (RXDX-101)	Drug: Entrectinib; TRKA/B/C, ROS1, and ALK inhibitor; Other Names: RXDX-101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD)	Assessed by National Cancer Institute Common Terminology for Adverse Events Criteria (NCI CTCAE v4.03)	Approximately 6 months
Recommended Phase 2 Dose (RP2D) of F1 Formulation In Pediatric Participants Able To Swallow Intact Capsules	Assessed by NCI CTCAE v4.03	Approximately 6 months
Recommended Phase 2 Dose (RP2D) of F06 Formulation In Pediatric Participants Able To Swallow Intact Capsules	Assessed by NCI CTCAE v4.03	Approximately 6 months
Recommended Phase 2 Dose (RP2D) of F06 Formulation In Pediatric In Participants Dosed Via Feeding Tube (Nasogastric Tube Or Gastric Tube)	Assessed by NCI CTCAE v4.03	Approximately 6 months
Recommended Phase 2 Dose (RP2D) Of Minitablets/F15 Formulation In Pediatric Participants Unable To Swallow Intact Capsules	Assessed by NCI CTCAE v4.03	Approximately 6 months
Cohort B: Objective Response Rate (ORR)	Assessed by RANO per the BICR	Approximately 6 months
Cohort D: ORR	Assessed by RECIST v1.1 per the BICR	Approximately 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability - AE, ECG and Labs assessed by NCI CTCAE v4.03	AE, ECG and Labs assessed by NCI CTCAE v4.03	Approximately 24 months
Maximum observed plasma drug concentration (Cmax) using F1 Formulation	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
Maximum observed plasma drug concentration (Cmax) using F06 Formulation given intact	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
Maximum observed plasma drug concentration (Cmax) using F06 Formulation administered via feeding tube	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
Maximum observed plasma drug concentration (Cmax) using minitablets/F15	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
Time to Cmax, by inspection (Tmax) using F1 Formulation	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
Time to Cmax, by inspection (Tmax) using F06 Formulation given intact	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
Time to Cmax, by inspection (Tmax) using F06 Formulation administered via feeding tube	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
Time to Cmax, by inspection (Tmax) using minitablets/F15	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
AUC at steady state (AUCss) using F1 Formulation	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
AUC at steady state (AUCss) using F06 Formulation given intact	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
AUC at steady state (AUCss) using F06 Formulation administered via feeding tube	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
AUC at steady state (AUCss) using minitablets/F15	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
Terminal half life (t½) using F1 Formulation	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
Terminal half life (t½) using F06 Formulation given intact	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
Terminal half life (t½) using F06 Formulation administered via feeding tube	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
Terminal half life (t½) using minitablets/F15	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
Area under the drug concentration by time curve (AUC) using F1 Formulation	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
Area under the drug concentration by time curve (AUC) using F06 Formulation given intact	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
Area under the drug concentration by time curve (AUC) using F06 Formulation administered via feeding tube	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
Area under the drug concentration by time curve (AUC) using minitablets/F15	Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter	Approximately 24 months
Cohort A, D, or E: Clinical Benefit Rate (CBR)	Assessed by RECIST v1.1 per the BICR and investigator	Approximately 6 months
Cohort B or E: CBR	Assessed by RANO per the BICR and investigator	Approximately 6 months
Cohort C: CBR	Assessed by the Curie scale per the BICR and investigator	Approximately 6 months
Cohort A, D, or E: Progression-free Survival (PFS)	Assessed by RECIST v1.1 per the BICR and investigator	Approximately 6 months
Cohort B or E: PFS	Assessed by RANO per the BICR and investigator	Approximately 6 months
Cohort C: PFS	Assessed by the Curie scale per the BICR and investigator	Approximately 6 months
Cohort A, D, or E: Overall Survival (OS)	Assessed by RECIST v1.1	Approximately 6 months
Cohort B or E: OS	Assessed by RANO	Approximately 6 months
Cohort A, D, or E: ORR	Assessed by RECIST v1.1 per the BICR and investigator	Approximately 6 months
Cohort B or E: ORR	Assessed by RANO per the BICR and investigator	Approximately 6 months
Cohort C: ORR	Assessed by the Curie scale per the BICR and investigator	Approximately 6 months
Cohort A, D, or E: Time to response (TTR)	Assessed by RECIST v1.1 per the BICR and investigator	Approximately 6 months
Cohort B or E: TTR	Assessed by RANO per the BICR and investigator	Approximately 6 months
Cohort C: TTR	Assessed by the Curie scale per the BICR and investigator	Approximately 6 months
Cohort A, D, or E: Duration of Response (DOR)	Assessed by RECIST v1.1 per the BICR and investigator	Approximately 6 months
Cohort B or E: DOR	Assessed by RANO per the BICR and investigator	Approximately 6 months
Cohort C: DOR	Assessed by the Curie scale per the BICR and investigator	Approximately 6 months
Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): ORR	Assessed by RANO per the investigator	Approximately 6 months
Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort D or E): ORR	Assessed by RECIST v1.1 per the investigator	Approximately 6 months
Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort A, D, or E): ORR	Assessed by RECIST v1.1 per the BICR and investigator	Approximately 6 months
Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort B or E): ORR	Assessed by RANO per the BICR and investigator	Approximately 6 months
Phase 1/2 Participants with ROS1 gene fusions (Cohort A, D, or E): ORR	Assessed by RECIST v1.1 per the BICR and investigator	Approximately 6 months
Phase 1/2 Participants with ROS1 gene fusions (Cohort B or E): ORR	Assessed by RANO per the BICR and investigator	Approximately 6 months
Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort A, D, or E): ORR	Assessed by RECIST v1.1 per the BICR and investigator	Approximately 6 months
Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): ORR	Assessed by RANO per the BICR and investigator	Approximately 6 months
Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): DOR	Assessed by RANO per the BICR and investigator	Approximately 6 months
Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort D or E): DOR	Assessed by RECIST v1.1 per the BICR and investigator	Approximately 6 months
Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort A, D, or E): DOR	Assessed by RECIST v1.1 per the BICR and investigator	Approximately 6 months
Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort B or E): DOR	Assessed by RANO per the BICR and investigator	Approximately 6 months
Phase 1/2 Participants with ROS1 gene fusions (Cohort A, D, or E): DOR	Assessed by RECIST v1.1 per the BICR and investigator	Approximately 6 months
Phase 1/2 Participants with ROS1 gene fusions (Cohort B or E): DOR	Assessed by RANO per the BICR and investigator	Approximately 6 months
Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort A, D, or E): DOR	Assessed by RECIST v1.1 per the BICR and investigator	Approximately 6 months
Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): DOR	Assessed by RANO per the BICR and investigator	Approximately 6 months
Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): TTR	Assessed by RANO per the BICR and investigator	Approximately 6 months
Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort D or E): TTR	Assessed by RECIST v1.1 per the BICR and investigator	Approximately 6 months
Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort A, D, or E): TTR	Assessed by RECIST v1.1 per the BICR and investigator	Approximately 6 months
Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort B or E): TTR	Assessed by RANO per the BICR and investigator	Approximately 6 months
Phase 1/2 Participants with ROS1 gene fusions (Cohort A, D, or E): TTR	Assessed by RECIST v1.1 per the BICR and investigator	Approximately 6 months
Phase 1/2 Participants with ROS1 gene fusions (Cohort B or E): TTR	Assessed by RANO per the BICR and investigator	Approximately 6 months
Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort A, D, or E): TTR	Assessed by RECIST v1.1 per the BICR and investigator	Approximately 6 months
Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): TTR	Assessed by RANO per the BICR and investigator	Approximately 6 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Desai AV, Robinson GW, Gauvain K, Basu EM, Macy ME, Maese L, Whipple NS, Sabnis AJ, Foster JH, Shusterman S, Yoon J, Weiss BD, Abdelbaki MS, Armstrong AE, Cash T, Pratilas CA, Corradini N, Marshall LV, Farid-Kapadia M, Chohan S, Devlin C, Meneses-Lorente G, Cardenas A, Hutchinson KE, Bergthold G, Caron H, Chow Maneval E, Gajjar A, Fox E. Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG). Neuro Oncol. 2022 Oct 3;24(10):1776-1789. doi: 10.1093/neuonc/noac087.
• Doebele RC, Drilon A, Paz-Ares L, Siena S, Shaw AT, Farago AF, Blakely CM, Seto T, Cho BC, Tosi D, Besse B, Chawla SP, Bazhenova L, Krauss JC, Chae YK, Barve M, Garrido-Laguna I, Liu SV, Conkling P, John T, Fakih M, Sigal D, Loong HH, Buchschacher GL Jr, Garrido P, Nieva J, Steuer C, Overbeck TR, Bowles DW, Fox E, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Demetri GD; trial investigators. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020 Feb;21(2):271-282. doi: 10.1016/S1470-2045(19)30691-6. Epub 2019 Dec 11.
• Desai AV, Bagchi A, Armstrong AE, van Tilburg CM, Basu EM, Robinson GW, Wang H, Casanova M, Andre N, Campbell-Hewson Q, Wu Y, Cardenas A, Ci B, Ryklansky C, Devlin CE, Meneses-Lorente G, Wulff J, Hutchinson KE, Gajjar A, Fox E. Efficacy and safety of entrectinib in children with extracranial solid or central nervous system (CNS) tumours harbouring NTRK or ROS1 fusions. Eur J Cancer. 2025 May 2;220:115308. doi: 10.1016/j.ejca.2025.115308. Epub 2025 Feb 22.

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2016
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: January 4, 2016
• First Submitted That Met QC Criteria: January 7, 2016
• First Posted (Estimated): January 8, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Pediatric; Relapsed; Refractory; Ewing sarcoma; Medulloblastoma; Solid Tumor; Metastatic Cancer; Sarcoma; Neuroblastoma; Papillary thyroid cancer; CNS tumors; ROS1; NTRK; ALK; Brain tumors; NTRK1; NTRK2; NTRK3; TRK; Tyrosine kinase; Gene rearrangement; Infantile fibrosarcoma; Secretory breast cancer; Congenital mesoblastic nephroma; Pontine glioma; Glial tumors; Salivary Gland Cancer (MASC); Wilms tumor (anaplastic)
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Mouth Diseases; Stomatognathic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Genetic Diseases, Inborn; Neoplasms by Histologic Type; Thyroid Neoplasms; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Neoplastic Processes; Urologic Neoplasms; Carcinoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Kidney Neoplasms; Salivary Gland Diseases; Neoplastic Syndromes, Hereditary; Neoplasms, Connective and Soft Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Complex and Mixed; Thyroid Diseases; Adenocarcinoma, Papillary; Mouth Neoplasms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Thyroid Cancer, Papillary; Recurrence; Neoplasm Metastasis; Glioma; Neuroblastoma; Sarcoma, Ewing; Sarcoma; Brain Neoplasms; Central Nervous System Neoplasms; Medulloblastoma; Wilms Tumor; Nephroma, Mesoblastic; Salivary Gland Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; entrectinib
• Other Study ID Numbers: RXDX-101-03; CO40778 (Other Identifier: Hoffmann-La Roche); 2023-505088-35-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing.