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Study of RXDX-101 in Children With Recurrent or Refractory Solid Tumors and Primary CNS Tumors, With or Without TRK, ROS1, or ALK Fusions

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Ignyta, Inc.
Sponsor:
Information provided by (Responsible Party):
Ignyta, Inc.
ClinicalTrials.gov Identifier:
NCT02650401
First received: January 4, 2016
Last updated: March 14, 2017
Last verified: March 2017
  Purpose
This is a 5-part, open-label, Phase 1/1b 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.

Condition Intervention Phase
Solid Tumors
CNS Tumors
Neuroblastoma
Drug: Entrectinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 1/1b, Open-Label, Dose-Escalation and Expansion Study of Entrectinib (RXDX 101) in Children and Adolescents With Recurrent or Refractory Solid Tumors and Primary CNS Tumors, With or Without TRK, ROS1, or ALK Fusions

Resource links provided by NLM:


Further study details as provided by Ignyta, Inc.:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: Approximately 6 months ]
    Assessed by National Cancer Institute Common Terminology for Adverse Events Criteria (NCI CTCAE v4.03)

  • Recommended Phase 2 Dose (RP2D) [ Time Frame: Approximately 6 months ]
    Assessed by NCI CTCAE v4.03


Secondary Outcome Measures:
  • Safety and Tolerability - AE, ECG and Labs assessed by NCI CTCAE v4.03 [ Time Frame: Approximately 24 months ]
    AE, ECG and Labs assessed by NCI CTCAE v4.03

  • Maximum observed plasma drug concentration (Cmax) [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained Day 1 (Cycles 1 and 2)

  • Time to Cmax, by inspection (Tmax) [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained Day 1 (Cycles 1 and 2)

  • Css [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained Day 1 (Cycles 1 and 2)

  • Terminal half life (t½) [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained Day 1 (Cycles 1 and 2)

  • Area under the drug concentration by time curve (AUC) [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained Day 1 (Cycles 1 and 2)

  • Objective Response Rate (ORR) [ Time Frame: Approximately 24 months ]
    Assessed by RECIST v1.1

  • Progression-free Survival (PFS) [ Time Frame: Approximately 24 months ]
    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


Estimated Enrollment: 190
Study Start Date: December 2015
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Extracranial solid tumors harboring NTRK1/2/3,

ROS1, ALK non-gene fusion molecular alterations

Oral entrectinib (RXDX-101)

Drug: Entrectinib
TRKA/B/C, ROS1, and ALK inhibitor
Other Name: RXDX-101
Active Comparator: CNS tumors harboring- NTRK1/2/3, ROS1, ALK

molecular alterations, including gene fusions

Oral entrectinib (RXDX-101)

Drug: Entrectinib
TRKA/B/C, ROS1, and ALK inhibitor
Other Name: RXDX-101
Active Comparator: Neuroblastoma
Oral entrectinib (RXDX-101)
Drug: Entrectinib
TRKA/B/C, ROS1, and ALK inhibitor
Other Name: RXDX-101
Active Comparator: Non-neuroblastoma, extracranial solid tumors

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

Oral entrectinib (RXDX-101)

Drug: Entrectinib
TRKA/B/C, ROS1, and ALK inhibitor
Other Name: RXDX-101
Active Comparator: Any patient unable to swallow capsules

who otherwise meet all other eligibility criteria

Oral entrectinib (RXDX-101)

Drug: Entrectinib
TRKA/B/C, ROS1, and ALK inhibitor
Other Name: RXDX-101

  Eligibility

Ages Eligible for Study:   2 Years to 22 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 age ≥ 2 years and < 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. Incomplete recovery from acute effects of any surgery prior to treatment.
  6. Active gastrointestinal disease or other malabsorption syndromes that would impact drug absorption.
  7. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02650401

Contacts
Contact: Vanessa Esquibel (858) 255-5959 ext 230 vesquibel@ignyta.com

Locations
United States, California
UCSD Rady Children's Hospital Recruiting
San Diego, California, United States, 92123
Contact: Janet Yoon, MD         
UCSF Benihoff Children's Recruiting
San Francisco, California, United States, 94143
Contact: Stephanie Schwartz    415-476-4923    stephanie.schwartz@ucsf.edu   
Contact: Amit Sabnis, MD         
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Margaret Macy, MD         
Contact: Debra Schissel    720-777-2879    debra.schissel@childrenscolorado.org   
United States, Georgia
Children's Healthcare of Atlanta Recruiting
Atlanta, Georgia, United States, 30322
Contact: Cynthia Wetmore, MD         
Contact: Jackie Smith    404-785-0692    Jaclyn.smith@choa.org   
United States, Illinois
Univ of Chicago Medical Center Not yet recruiting
Chicago, Illinois, United States, 60615
Contact: Ami Desai, MD         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Cecilia Carlowicz    617-632-4931    ccarlowicz@partners.org   
Contact: Suzanne Shusterman, MD         
United States, Minnesota
Univ of Minnesota Medical Center Not yet recruiting
Minneapolis, Minnesota, United States, 55454
Contact: Brenda Weigel, MD         
United States, Missouri
Washington Univ School of Medicine Not yet recruiting
Saint Louis, Missouri, United States, 63110
Contact: Karen Gauvain, MD         
United States, New York
Columbia Univ Ped Hem/Onc Not yet recruiting
New York, New York, United States, 10032
Contact: Julia Glade Bender, MD         
Memorial Sloan Kettering Recruiting
New York, New York, United States, 10065
Contact: Julianne Cameron    646-888-5717    cameronj@mskcc.org   
Contact: Ellen Basu, MD         
United States, Ohio
Cincinnati Children's Hospital Not yet recruiting
Cincinnati, Ohio, United States, 45229
Contact: Brian Weiss, MD         
Nationwide Children's Hospital Not yet recruiting
Columbus, Ohio, United States, 43205
Contact: Mohamad S. AdbelBaki, MD, NeuroOnc         
United States, Oregon
Oregon Health Science University Not yet recruiting
Portland, Oregon, United States, 97239
Contact: Rebecca Loret De Mola, DO, MCR         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Joseph Gottschalk    267-426-9293 ext 69293      
Contact: Elizabeth Fox, MD         
United States, Tennessee
St. Jude Children's Research Hospital Not yet recruiting
Memphis, Tennessee, United States, 38105
Contact: Amar Gajjar, MD         
United States, Texas
Cook Children's Hospital Not yet recruiting
Fort Worth, Texas, United States, 76104
Contact: Kelly Vallance, MD         
Texas Children's Cancer, Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Renee Klenke    832-824-4646    raklenke@txch.org   
Contact: Jennifer Foster, MD, MPH         
United States, Utah
Univ of Utah, Primary Children's Hospital Not yet recruiting
Salt Lake City, Utah, United States, 84113
Contact: Luke Maese, DO         
Sponsors and Collaborators
Ignyta, Inc.
Investigators
Study Director: Edna Chow Maneval, PhD Ignyta, Inc.
  More Information

Responsible Party: Ignyta, Inc.
ClinicalTrials.gov Identifier: NCT02650401     History of Changes
Other Study ID Numbers: RXDX-101-03
Study First Received: January 4, 2016
Last Updated: March 14, 2017

Keywords provided by Ignyta, Inc.:
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)

Additional relevant MeSH terms:
Neoplasms
Neuroblastoma
Central Nervous System Neoplasms
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
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases

ClinicalTrials.gov processed this record on May 25, 2017