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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

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ClinicalTrials.gov Identifier: NCT02650401
Recruitment Status : Recruiting
First Posted : January 8, 2016
Last Update Posted : February 8, 2018
Sponsor:
Information provided by (Responsible Party):
Ignyta, Inc.

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
Study Start Date : December 2015
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : March 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

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

  Show 21 Study Locations
Sponsors and Collaborators
Ignyta, Inc.
Investigators
Study Director: Edna Chow Maneval, PhD Ignyta, Inc.

Responsible Party: Ignyta, Inc.
ClinicalTrials.gov Identifier: NCT02650401     History of Changes
Other Study ID Numbers: RXDX-101-03
First Posted: January 8, 2016    Key Record Dates
Last Update Posted: February 8, 2018
Last Verified: February 2018

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