ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02650401
Recruitment Status : Recruiting
First Posted : January 8, 2016
Last Update Posted : June 18, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
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 or disease Intervention/treatment Phase
Solid Tumors CNS Tumors Neuroblastoma Drug: Entrectinib Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 190 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
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
Actual Study Start Date : May 3, 2016
Estimated Primary Completion Date : September 30, 2018
Estimated Study Completion Date : March 31, 2019


Arm Intervention/treatment
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




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

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


Secondary Outcome Measures :
  1. 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

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

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

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

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

  6. 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)

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

  8. 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



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02650401


Contacts
Contact: Reference Study ID Number: CO40778 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
United States, California
Children'S Hospital of Orange County Recruiting
Orange, California, United States, 92868-3874
Rady Childrens Hospital Recruiting
San Diego, California, United States, 92123
UCSF Benioff Children's Hospital; UCSF Pediatrics Hematology Oncology Recruiting
San Francisco, California, United States, 94158
United States, Colorado
Children's Hospital Colorado; Center For Cancer/Blood Disorder Recruiting
Aurora, Colorado, United States, 80045
United States, District of Columbia
Children's National Medical Center; Department of Pediatrics Not yet recruiting
Washington, District of Columbia, United States, 20037
United States, Georgia
Egleston Children's Hospital at Emory University Atlanta; Pediatric Hematology/Oncology Recruiting
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Chicago; Comer Children's Hospital/Department of Pediatrics Recruiting
Chicago, Illinois, United States, 60637
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, Minnesota
University of Minnesota Childrens' Hospital Recruiting
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University,St. Louis Children's Hospital; Neurology, Movement Disorder Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Morgan Stanley Children's Hospital; Herbert Irving Cancer Center Recruiting
New York, New York, United States, 10032
Memorial Sloan Kettering Cancer Center; Pediatrics Recruiting
New York, New York, United States, 10065
United States, Ohio
Nationwide Children's Hospital; Dept. of Pulmonology Recruiting
Columbus, Ohio, United States, 43205
United States, Oregon
Oregon Health & Science Uni Recruiting
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
St. Jude Children'S Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
United States, Texas
Cook Childrens Medical Center Recruiting
Fort Worth, Texas, United States, 76104
Texas Children's Cancer and Hematology Center Recruiting
Houston, Texas, United States, 77030
United States, Utah
Primary Children's Hospital Recruiting
Salt Lake City, Utah, United States, 84113
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02650401     History of Changes
Other Study ID Numbers: RXDX-101-03
CO40778 ( Other Identifier: Hoffmann-La Roche )
First Posted: January 8, 2016    Key Record Dates
Last Update Posted: June 18, 2018
Last Verified: June 2018

Keywords provided by Hoffmann-La Roche:
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