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

NCT ID: NCT02650401

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

69 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-03

Study Completion Date

2026-06-30

Brief Summary

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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.

Detailed Description

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Conditions

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Solid Tumors CNS Tumors

Keywords

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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)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CNS tumors harboring- NTRK1/2/3, ROS1, ALK

Arm closed for further enrollment

molecular alterations, including gene fusions

Oral entrectinib (RXDX-101)

Group Type ACTIVE_COMPARATOR

Entrectinib

Intervention Type DRUG

TRKA/B/C, ROS1, and ALK inhibitor

Neuroblastoma

Arm closed for further enrollment

Oral entrectinib (RXDX-101)

Group Type ACTIVE_COMPARATOR

Entrectinib

Intervention Type DRUG

TRKA/B/C, ROS1, and ALK inhibitor

Non-neuroblastoma, extracranial solid tumors

Arm closed for further enrollment

harboring - NTRK1/2/3, ROS1, ALK gene fusions

Oral entrectinib (RXDX-101)

Group Type ACTIVE_COMPARATOR

Entrectinib

Intervention Type DRUG

TRKA/B/C, ROS1, and ALK inhibitor

Any participant unable to swallow capsules

Arm closed for further enrollment

Any participant who otherwise meet all other eligibility criteria

Oral entrectinib (RXDX-101)

Group Type ACTIVE_COMPARATOR

Entrectinib

Intervention Type DRUG

TRKA/B/C, ROS1, and ALK inhibitor

Expansion: CNS tumors harboring NTRK1/2/3, ROS1

gene fusions

Oral entrectinib (RXDX-101)

Group Type ACTIVE_COMPARATOR

Entrectinib

Intervention Type DRUG

TRKA/B/C, ROS1, and ALK inhibitor

Expansion: Extracranial solid tumors harboring NTRK1/2/3, ROS1

NTRK 1,2,3 and ROS1 fusions

Oral entrectinib (RXDX-101)

Group Type ACTIVE_COMPARATOR

Entrectinib

Intervention Type DRUG

TRKA/B/C, ROS1, and ALK inhibitor

Extracranial solid tumors harboring NTRK1/2/3,

Arm closed for further enrollment

ROS1, ALK non-gene fusion molecular alterations

Oral entrectinib (RXDX-101)

Group Type ACTIVE_COMPARATOR

Entrectinib

Intervention Type DRUG

TRKA/B/C, ROS1, and ALK inhibitor

Interventions

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Entrectinib

TRKA/B/C, ROS1, and ALK inhibitor

Intervention Type DRUG

Other Intervention Names

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RXDX-101

Eligibility Criteria

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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.
Minimum Eligible Age

0 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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University of California San Diego

La Jolla, California, United States

Site Status

UCSF Benioff Children's Hospital

San Francisco, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Egleston Children's Hospital at Emory University Atlanta

Atlanta, Georgia, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Washington University,St. Louis Children's Hospital

St Louis, Missouri, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Oregon Health & Science Uni

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

St. Jude Children'S Research Hospital

Memphis, Tennessee, United States

Site Status

Texas Children's Cancer and Hematology Center

Houston, Texas, United States

Site Status

Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status

The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Site Status

Beijing Children's Hospital, Capital Medical University

Beijing, , China

Site Status

Centre Leon Berard

Lyon, , France

Site Status

Hôpital de la Timone, Oncologie Pédiatrique

Marseille, , France

Site Status

Universitaetsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Site Status

Hong Kong Children's Hospital

Hong Kong, , Hong Kong

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Lombardy, Italy

Site Status

Hospital Infantil Universitario Nino Jesus

Madrid, , Spain

Site Status

Royal Marsden Hospital (Sutton)

London, , United Kingdom

Site Status

Royal Victoria Infirmary

Newcastle upon Tyne, , United Kingdom

Site Status

Countries

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South Korea Taiwan United States Canada China France Germany Hong Kong Italy Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 40086048 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35395680 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31838007 (View on PubMed)

Other Identifiers

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CO40778

Identifier Type: OTHER

Identifier Source: secondary_id

2023-505088-35-00

Identifier Type: CTIS

Identifier Source: secondary_id

RXDX-101-03

Identifier Type: -

Identifier Source: org_study_id