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Trial record 1 of 1 for:    NCT02650401
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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 (STARTRK-NG)

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 : September 25, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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.

Condition or disease Intervention/treatment Phase
Solid Tumors CNS Tumors Drug: Entrectinib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 68 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open-Label, Dose-Escalation And Expansion Study Of Entrectinib (Rxdx-101) In Pediatrics With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options
Actual Study Start Date : May 3, 2016
Estimated Primary Completion Date : June 1, 2023
Estimated Study Completion Date : June 1, 2023


Arm Intervention/treatment
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)

Drug: Entrectinib
TRKA/B/C, ROS1, and ALK inhibitor
Other Name: 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)

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

Active Comparator: Neuroblastoma

Arm closed for further enrollment

Oral entrectinib (RXDX-101)

Drug: Entrectinib
TRKA/B/C, ROS1, and ALK inhibitor
Other Name: 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)

Drug: Entrectinib
TRKA/B/C, ROS1, and ALK inhibitor
Other Name: 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)

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

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

gene fusions

Oral entrectinib (RXDX-101)

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

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

NTRK 1,2,3 and ROS1 fusions

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) of F1 Formulation In Pediatric Participants Able To Swallow Intact Capsules [ Time Frame: Approximately 6 months ]
    Assessed by NCI CTCAE v4.03

  3. Recommended Phase 2 Dose (RP2D) of F06 Formulation In Pediatric Participants Able To Swallow Intact Capsules [ Time Frame: Approximately 6 months ]
    Assessed by NCI CTCAE v4.03

  4. Recommended Phase 2 Dose (RP2D) of F06 Formulation In Pediatric In Participants Dosed Via Feeding Tube (Nasogastric Tube Or Gastric Tube) [ Time Frame: Approximately 6 months ]
    Assessed by NCI CTCAE v4.03

  5. Recommended Phase 2 Dose (RP2D) Of Minitablets/F15 Formulation In Pediatric Participants Unable To Swallow Intact Capsules [ Time Frame: Approximately 6 months ]
    Assessed by NCI CTCAE v4.03

  6. Objective Response Rate (ORR) [ Time Frame: Approximately 6 months ]
    Assessed by RECIST v1.1


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) using F1 Formulation [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  3. Maximum observed plasma drug concentration (Cmax) using F06 Formulation given intact [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  4. Maximum observed plasma drug concentration (Cmax) using F06 Formulation administered via feeding tube [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  5. Maximum observed plasma drug concentration (Cmax) using minitablets/F15 [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  6. Time to Cmax, by inspection (Tmax) using F1 Formulation [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  7. Time to Cmax, by inspection (Tmax) using F06 Formulation given intact [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  8. Time to Cmax, by inspection (Tmax) using F06 Formulation administered via feeding tube [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  9. Time to Cmax, by inspection (Tmax) using minitablets/F15 [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  10. AUC at steady state (AUCss) using F1 Formulation [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  11. AUC at steady state (AUCss) using F06 Formulation given intact [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  12. AUC at steady state (AUCss) using F06 Formulation administered via feeding tube [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  13. AUC at steady state (AUCss) using minitablets/F15 [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  14. Terminal half life (t½) using F1 Formulation [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  15. Terminal half life (t½) using F06 Formulation given intact [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  16. Terminal half life (t½) using F06 Formulation administered via feeding tube [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  17. Terminal half life (t½) using minitablets/F15 [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  18. Area under the drug concentration by time curve (AUC) using F1 Formulation [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  19. Area under the drug concentration by time curve (AUC) using F06 Formulation given intact [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  20. Area under the drug concentration by time curve (AUC) using F06 Formulation administered via feeding tube [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  21. Area under the drug concentration by time curve (AUC) using minitablets/F15 [ Time Frame: Approximately 24 months ]
    Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter

  22. Progression-free Survival (PFS) [ Time Frame: Approximately 6 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

  23. Overall Survival (OS) [ Time Frame: Approximately 6 months ]
    Assessed by RECIST v1.1

  24. Duration of Response (DOR) [ Time Frame: Approximately 6 months ]
    Assessed by RECIST v1.1

  25. Time to response (TTR) [ Time Frame: Approximately 6 months ]
    Assessed by RECIST v1.1

  26. Clinical Benefit Rate (CBR) [ Time Frame: Approximately 6 months ]
    Assessed by RECIST v1.1



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.


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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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
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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
Show Show 35 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02650401    
Other Study ID Numbers: RXDX-101-03
CO40778 ( Other Identifier: Hoffmann-La Roche )
First Posted: January 8, 2016    Key Record Dates
Last Update Posted: September 25, 2020
Last Verified: September 2020
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:
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Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Entrectinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action