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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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 0 Years - 18 Years
Gender All
More Inclusion & Exclusion Criteria

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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT02650401
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Hoffmann-La Roche
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Clinical Trials
Principal Investigator Affiliation Hoffmann-La Roche
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Active, not recruiting
Countries Canada, China, France, Germany, Hong Kong, Italy, Korea, Republic of, Spain, Taiwan, United Kingdom, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Solid Tumors, CNS Tumors
Arms & Interventions

Arms

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)

Active Comparator: CNS tumors harboring- NTRK1/2/3, ROS1, ALK

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

Active Comparator: Neuroblastoma

Arm closed for further enrollment Oral entrectinib (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)

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)

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

gene fusions Oral entrectinib (RXDX-101)

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

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

Interventions

Drug: - Entrectinib

TRKA/B/C, ROS1, and ALK inhibitor

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Children'S Hospital of Orange County, Orange, California

Status

Address

Children'S Hospital of Orange County

Orange, California, 92868-3874

Rady Childrens Hospital, San Diego, California

Status

Address

Rady Childrens Hospital

San Diego, California, 92123

San Francisco, California

Status

Address

UCSF Benioff Children's Hospital; UCSF Pediatrics Hematology Oncology

San Francisco, California, 94158

Aurora, Colorado

Status

Address

Children's Hospital Colorado; Center For Cancer/Blood Disorder

Aurora, Colorado, 80045

Washington, District of Columbia

Status

Address

Children's National Medical Center; Department of Pediatrics

Washington, District of Columbia, 20037

Atlanta, Georgia

Status

Address

Egleston Children's Hospital at Emory University Atlanta; Pediatric Hematology/Oncology

Atlanta, Georgia, 30322

Chicago, Illinois

Status

Address

University of Chicago; Comer Children's Hospital/Department of Pediatrics

Chicago, Illinois, 60637

Johns Hopkins University, Baltimore, Maryland

Status

Address

Johns Hopkins University

Baltimore, Maryland, 21205

Dana Farber Cancer Institute, Boston, Massachusetts

Status

Address

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

Minneapolis, Minnesota

Status

Address

University of Minnesota Childrens' Hospital

Minneapolis, Minnesota, 55455

Saint Louis, Missouri

Status

Address

Washington University,St. Louis Children's Hospital; Neurology, Movement Disorder

Saint Louis, Missouri, 63110

New York, New York

Status

Address

Morgan Stanley Children's Hospital; Herbert Irving Cancer Center

New York, New York, 10032

New York, New York

Status

Address

Memorial Sloan Kettering Cancer Center; Pediatrics

New York, New York, 10065

Cincinnati, Ohio

Status

Address

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229

Columbus, Ohio

Status

Address

Nationwide Children's Hospital; Dept. of Pulmonology

Columbus, Ohio, 43205

Oregon Health & Science Uni, Portland, Oregon

Status

Address

Oregon Health & Science Uni

Portland, Oregon, 97239

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

Status

Address

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104

St. Jude Children'S Research Hospital, Memphis, Tennessee

Status

Address

St. Jude Children'S Research Hospital

Memphis, Tennessee, 38105

Cook Childrens Medical Center, Fort Worth, Texas

Status

Address

Cook Childrens Medical Center

Fort Worth, Texas, 76104

Houston, Texas

Status

Address

Texas Children's Cancer and Hematology Center

Houston, Texas, 77030

Primary Children's Hospital, Salt Lake City, Utah

Status

Address

Primary Children's Hospital

Salt Lake City, Utah, 84113

International Sites

The Hospital for Sick Children, Toronto, Ontario, Canada

Status

Address

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8

Beijing City, China

Status

Address

Beijing Children's Hospital, Capital Medical University; Oncological Surgery Department

Beijing City, , 100032

Shanghai, China

Status

Address

Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, , 200092

Centre Leon Berard; Pediatrie, Lyon, France

Status

Address

Centre Leon Berard; Pediatrie

Lyon, , 69373

Marseille, France

Status

Address

Hôpital de la Timone, Oncologie Pédiatrique

Marseille, , 13385

Toulouse, France

Status

Address

Hopital Purpan; Pediatrie - Hematologie - Oncologie pediatrique

Toulouse, , 31500

Villejuif, France

Status

Address

Institut Gustave Roussy; Service de Pathologie Morphologique

Villejuif, , 94805

Universitaetsklinikum Heidelberg, Heidelberg, Germany

Status

Address

Universitaetsklinikum Heidelberg

Heidelberg, , 69120

Hong Kong Children's Hospital, Hong Kong, Hong Kong

Status

Address

Hong Kong Children's Hospital

Hong Kong, ,

Milano, Lombardia, Italy

Status

Address

Fondazione IRCCS Istituto Nazionale dei Tumori; Struttura Complessa di Pediatria Oncologica

Milano, Lombardia, 20133

Torino, Piemonte, Italy

Status

Address

A. O. Città della Salute e della Scienza di Torino; SC Oncoematologia e Centro Trapianti AOOIRM

Torino, Piemonte, 10126

Seoul National University Hospital, Seoul, Korea, Republic of

Status

Address

Seoul National University Hospital

Seoul, , 03080

Esplugues de Llobregat, Barcelona, Spain

Status

Address

Hospital Sant Joan de Deu; Servicio de Oncologia y Hematologia

Esplugues de Llobregat, Barcelona, 08950

Madrid, Spain

Status

Address

Hospital Infantil Universitario Nino Jesus

Madrid, , 28009

Taipei, Taiwan

Status

Address

National Taiwan University Hospital; Department of Paediatrics

Taipei, , 100

Taoyuan City, Taiwan

Status

Address

Chang Gung Memorial Hospital, Linkou; Department of Pediatric Internal Medicine

Taoyuan City, , 333

Leeds General Infirmary, Leeds, United Kingdom

Status

Address

Leeds General Infirmary

Leeds, , LS1 3EX

Royal Victoria Infirmary; Pharmacy, Newcastle upon Tyne, United Kingdom

Status

Address

Royal Victoria Infirmary; Pharmacy

Newcastle upon Tyne, , NE1 4LP

Royal Marsden NHS Foundation Trust, Sutton, United Kingdom

Status

Address

Royal Marsden NHS Foundation Trust

Sutton, , SM2 5PT