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 | Active Not Recruiting Phase 1 DMC

• 3 other identifiers: RXDX-101-03CO407782023-505088-35-00
• Study Type: interventional
• Target: 69
• Locations: 9 countries
• Sites: 26

Brief Summary

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.

Conditions

Solid Tumors; CNS Tumors

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)

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (62)

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

  Approximately 24 months

• Maximum observed plasma drug concentration (Cmax) using F1 Formulation

  Approximately 24 months

• Maximum observed plasma drug concentration (Cmax) using F06 Formulation given intact

  Approximately 24 months

• Maximum observed plasma drug concentration (Cmax) using F06 Formulation administered via feeding tube

  Approximately 24 months

• Maximum observed plasma drug concentration (Cmax) using minitablets/F15

  Approximately 24 months

Study Arms (7)

Extracranial solid tumors harboring NTRK1/2/3,

ACTIVE COMPARATOR

Arm closed for further enrollment ROS1, ALK non-gene fusion molecular alterations Oral entrectinib (RXDX-101)

Drug: Entrectinib

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

ACTIVE COMPARATOR

Arm closed for further enrollment molecular alterations, including gene fusions Oral entrectinib (RXDX-101)

Drug: Entrectinib

Neuroblastoma

ACTIVE COMPARATOR

Arm closed for further enrollment Oral entrectinib (RXDX-101)

Drug: Entrectinib

Non-neuroblastoma, extracranial solid tumors

ACTIVE COMPARATOR

Arm closed for further enrollment harboring - NTRK1/2/3, ROS1, ALK gene fusions Oral entrectinib (RXDX-101)

Drug: Entrectinib

Any participant unable to swallow capsules

ACTIVE COMPARATOR

Arm closed for further enrollment Any participant who otherwise meet all other eligibility criteria Oral entrectinib (RXDX-101)

Drug: Entrectinib

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

ACTIVE COMPARATOR

gene fusions Oral entrectinib (RXDX-101)

Drug: Entrectinib

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

ACTIVE COMPARATOR

NTRK 1,2,3 and ROS1 fusions Oral entrectinib (RXDX-101)

Drug: Entrectinib

Interventions

Entrectinib DRUG

TRKA/B/C, ROS1, and ALK inhibitor

Also known as: RXDX-101

Any participant unable to swallow capsules; CNS tumors harboring- NTRK1/2/3, ROS1, ALK; Expansion: CNS tumors harboring NTRK1/2/3, ROS1; Expansion: Extracranial solid tumors harboring NTRK1/2/3, ROS1; Extracranial solid tumors harboring NTRK1/2/3,; Neuroblastoma; Non-neuroblastoma, extracranial solid tumors

Eligibility Criteria

• Age: 0 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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
• Histologic/molecular diagnosis of malignancy at diagnosis or the time of relapse
• Archival tumor tissue from diagnosis or, preferably, at relapse

You may not qualify if:

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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (26)

University of California San Diego

La Jolla, California, 92093-0706, United States

Location

UCSF Benioff Children's Hospital

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Egleston Children's Hospital at Emory University Atlanta

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Washington University,St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health & Science Uni

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Children'S Research Hospital

Memphis, Tennessee, 38105, United States

Location

Texas Children's Cancer and Hematology Center

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200082, China

Location

Beijing Children's Hospital, Capital Medical University

Beijing, China

Location

Centre Leon Berard

Lyon, 69373, France

Location

Hôpital de la Timone, Oncologie Pédiatrique

Marseille, 13385, France

Location

Universitaetsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Hong Kong Children's Hospital

Hong Kong, 00000, Hong Kong

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Lombardy, 20133, Italy

Location

Hospital Infantil Universitario Nino Jesus

Madrid, 28009, Spain

Location

Royal Marsden Hospital (Sutton)

London, SW3 6JJ, United Kingdom

Location

Royal Victoria Infirmary

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 40086048 DERIVED

• 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.

  PMID: 35395680 DERIVED

• 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.

  PMID: 31838007 DERIVED

MeSH Terms

Conditions

Central Nervous System Neoplasms; Recurrence; Neoplasm Metastasis; Neuroblastoma; Nephroma, Mesoblastic; Brain Neoplasms; Sarcoma; Sarcoma, Ewing; Glioma; Salivary Gland Neoplasms; Thyroid Cancer, Papillary; Medulloblastoma; Wilms Tumor

Interventions

entrectinib

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Brain Diseases; Central Nervous System Diseases; Neoplasms, Connective and Soft Tissue; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Mouth Neoplasms; Head and Neck Neoplasms; Mouth Diseases; Stomatognathic Diseases; Salivary Gland Diseases; Adenocarcinoma, Papillary; Adenocarcinoma; Carcinoma; Thyroid Neoplasms; Endocrine Gland Neoplasms; Endocrine System Diseases; Thyroid Diseases; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2016
• First Posted: January 8, 2016
• Study Start: May 3, 2016
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

ES (1); GB (2); CN (2); FR (2); CA (1); US (15); DE (1); HK (1); IT (1)