Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children (SCOUT)

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: NCT02637687
Recruitment Status : Recruiting
First Posted : December 22, 2015
Last Update Posted : May 11, 2022
Sponsor:
Information provided by (Responsible Party):
Bayer

Tracking Information
First Submitted Date  ICMJE December 10, 2015
First Posted Date  ICMJE December 22, 2015
Last Update Posted Date May 11, 2022
Actual Study Start Date  ICMJE December 16, 2015
Estimated Primary Completion Date July 1, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 9, 2021)
  • Phase 1: Number of participants in an assigned dose cohort with treatment emergent adverse events (TEAEs) by grade assessed by NCI-CTCAE v 4.03 who experience a DLT [ Time Frame: From Day 1 to Day 28 of Cycle 1 (1 Cycle=28 days) ]
    DLT: Dose-limiting toxicity. NCI-CTCAE: National Cancer Institute-Common Terminology Criteria for Adverse Events.
  • Phase 1: Number of participants with TEAEs [ Time Frame: From first dose of larotrectinib up to 93 months ]
  • Phase 1: Severity of TEAEs [ Time Frame: From first dose of larotrectinib up to 93 months ]
  • Phase 2: Overall response rate (ORR) by IRRC [ Time Frame: From first dose of Larotrectinib to disease progression or subsequent therapy or surgical intervention or death, up to 76 months ]
    Proportion of participants with a best overall response of complete response (CR) or partial response (PR) as determined by an independent radiology review committee (IRRC) based on Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, Response Assessment in Neuro Oncology (RANO) or International Neuroblastoma Response Criteria (INRC) as appropriate to tumor type who express NTRK gene fusions.
Original Primary Outcome Measures  ICMJE
 (submitted: December 18, 2015)
Determine dose-limiting toxicity (DLT), in pediatric patients with advanced solid or primary central nervous system (CNS) tumors, as assessed by CTCAE v4.0 [ Time Frame: 6 Months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2021)
  • Phase 1: Maximum concentration of larotrectinib in plasma (Cmax) [ Time Frame: Cohort 1 and 2: Cycle 1 Day 1 (C1D1) at 1 and 4 hours post-dose and C2D1 at pre-dose, and at 1 and 4 hours post-dose; Cohort 3 and Dose Expansion Cohort: C1D1 at 1 and 4 hours post-dose and C4D1 at pre-dose, 1 and 4 hours post-dose ]
  • Phase 1: Area under the concentration versus time curve from time 0 to t (AUC0-t) of larotrectinib in plasma [ Time Frame: Cohort 1 and 2: C1D1 at 1 and 4 hours post-dose and C2D1 at pre-dose, and at 1 and 4 hours post-dose; Cohort 3 and Dose Expansion Cohort: C1D1 at 1 and 4 hours post-dose and C4D1 at pre-dose, 1 and 4 hours post-dose ]
  • Phase 1: Oral clearance (CL/F) [ Time Frame: Cohort 1 and 2: C1D1 at 1 and 4 hours post-dose and C2D1 at pre-dose, and at 1 and 4 hours post-dose; Cohort 3 and Dose Expansion Cohort: C1D1 at 1 and 4 hours post-dose and C4D1 at pre-dose, 1 and 4 hours post-dos ]
  • Phase 1: Cerebral spinal fluid/plasma ratio of larotrectinib [ Time Frame: C1D1 in conjunction with the post-dose 1-hour PK sample ]
  • Phase 1: Maximum tolerated dose (MTD) [ Time Frame: From C1D1 to C1D28 of treatment of each participant in each of the assigned dose cohort, up to 16 months ]
  • Phase 1: Recommended dose for Phase 2 [ Time Frame: From the date a participants from assigned Cohort was administered the first dose to the date of the last dose for the last patient from the dose escalation phase, up to 16 months ]
  • Phase 1: Overall Response Rate (ORR) [ Time Frame: From first dose of Larotrectinib to disease progression or subsequent therapy or surgical intervention or death (due to any cause), up to 93 months ]
    Proportion of participants with best overall response (BOR) of CR and PR; PFS, CBR and maximum change in tumor burden as assessed based on RECIST 1.1, INRC or RANO as appropriate for tumor type by IRRC.
  • Phase 1: Mean change from baseline in Pain scores as assessed by the Wong-Baker Faces scale [ Time Frame: Baseline and D1 of every cycle (1 Cycle=28 days), up to 93 months ]
    Wong-Baker Faces Scale giving a pain scale between 0 (no hurt) to 10 (hurts worst).
  • Phase 1: Mean change in Health-related quality of life scores by PedsQL-Core [ Time Frame: Baseline and D1 of every cycle (1 Cycle=28 days), Up to 93 months ]
    The health-related quality of life (HRQoL) is assessed with the Pediatrics Quality of Life - Core Module (PedsQL-Core) questionnaire that consists of various age-related items regarding physical, emotional, social and school functioning and gives an overall score between 0 (highest HRQoL) and 144 (lowest HRQoL).
  • Phase 2: Best overall response (BOR) [ Time Frame: From first dose of Larotrectinib to disease progression or subsequent therapy or surgical intervention or death (due to any cause), up to 76 months ]
    Participants with best overall response (BOR) of either CR or PR determined by Investigator's or IRC's response assessment based on RANO, INRC and RECIST 1.1 as appropriate for tumor type
  • Phase 2: Duration of response (DOR) [ Time Frame: From start of first objective response of confirmed CR or PR to progression or death (due to any cause), up to 76 months ]
    DOR determined by 1) an independent radiology review committee and 2) the treating Investigator.
  • Phase 2: Proportion of patients with any tumor regression (i.e., any decrease from baseline of the longest diameters of target lesions) as a best response [ Time Frame: From first dose of Larotrectinib, up to 76 months ]
  • Phase 2: Progression-free survival (PFS) [ Time Frame: From first dose of Larotrectinib to disease progression or subsequent therapy or surgical intervention or death (due to any cause), up to 112 months ]
  • Phase 2: Overall survival (OS) [ Time Frame: From first dose of Larotrectinib to death (due to any cause), up to 112 months ]
  • Phase 2: Number of participants with Treatment emergent adverse events (TEAEs) [ Time Frame: From first dose of larotrectinib to discontinuation of treatment or death (due to any cayse), up to 112 months ]
  • Phase 2: Severity of adverse events as assessed by NCI-CTCAE grading V 4.03 [ Time Frame: From first dose of larotrectinib to discontinuation of treatment or death (due to any cause), up to 112 months ]
  • Phase 2: Clinical Benefit Rate (CBR) [ Time Frame: From first dose of Larotrectinib to disease progression or subsequent therapy or surgical intervention or death (due to any cause), up to 76 months ]
    CBR (i.e., best overall response of CR, PR or SD lasting 16 weeks or more as determined by 1) an independent radiology review committee (IRC) and 2) by the treating Investigator.
  • Phase 2: Concordance coefficient [ Time Frame: From baseline/screening and if feasible end of treatment (EOT) and or PD and or at re-start of study treatment following a "drug holiday" and disease recurrence, up to 112 months ]
    Concordance coefficient of intra-patient molecular profile
  • Phase 2: Post-operative tumor staging [ Time Frame: From first dose of Larotrectinib to surgical intervention, up to 112 months ]
    Post-operative stage in patients treated with larotrectinib according to the TNM Classification of malignant tumors of the Union for International Cancer Control (UICC).
  • Phase 2: Post-operative surgical margin assessment [ Time Frame: From first dose of Larotrectinib to surgical intervention, up to 112 months ]
    Surgical margin status in patients treated with larotrectinib using the International Cancer Control (UICC)-R classification and the Intergroup Rhabdomyosarcoma Staging (IRS) systems.
  • Phase 2: Pre-treatment surgical plan to preserve function and cosmetic outcome [ Time Frame: From first dose of Larotrectinib to surgical intervention, up to 112 months ]
    Descriptive analysis of pretreatment surgical plan.
  • Phase 2: Post-treatment plans to conserve function and cosmetic outcome [ Time Frame: From surgical intervention to subsequent therapy, up to 112 months ]
    Descriptive analysis of post-treatment plans
Original Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2015)
  • To characterize the pharmacokinetic (PK) properties of LOXO-101 in pediatric patients with advanced solid or primary CNS tumors including Peak Plasma Concentration (Cmax), following BID dosing [ Time Frame: 6 Months ]
  • To characterize the pharmacokinetic (PK) properties of LOXO-101 in pediatric patients with advanced solid or primary CNS tumors including Time (TMax) at which the Peak Plasma Concentration (Cmax) is observed, following BID dosing [ Time Frame: 6 Months ]
  • To characterize the pharmacokinetic (PK) properties of LOXO-101 in pediatric patients with advanced solid or primary CNS tumors including the Half Life of LOXO-101, following BID dosing [ Time Frame: 6 Months ]
  • To characterize the pharmacokinetic (PK) properties of LOXO-101 in pediatric patients with advanced solid or primary CNS tumors including Area under the plasma concentration versus time curve (AUC) following BID dosing [ Time Frame: 6 Months ]
  • To identify the recommended Phase 2 Dose (RP2D) of LOXO-101 for further clinical investigation in this patient population [ Time Frame: 6 Months ]
  • Proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the Investigator. [ Time Frame: 6 Months ]
  • Change From Baseline in Pain Scores on the Visual Analog Scale based on final assessment [ Time Frame: 6 Months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children
Official Title  ICMJE A Phase 1/2 Study of the Oral TRK Inhibitor Larotrectinib in Pediatric Patients With Advanced Solid or Primary Central Nervous System Tumors
Brief Summary

The study is being done to test the safety of a cancer drug called larotrectinib in children. The cancer must have a change in a particular gene (NTRK1, NTRK2 or NTRK3). Larotrectinib blocks the actions of these NTRK genes in cancer cells and can therefore be used to treat cancer.

The first study part (Phase 1) is done to determine what dose level of larotrectinib is safe for children, how the drug is absorbed and changed by their bodies and how well the cancer responds to the drug. The main purpose of the second study part (Phase 2) is to investigate how well and how long different cancer types respond to the treatment with larotrectininb.

Detailed Description

The primary objectives are to determine the safety and efficacy of oral larotrectinib in pediatric patients with advanced solid or primary central nervous system (CNS) tumors.

The secondary objectives comprise e.g. the determination of the pharmacokinetic properties, the maximum tolerated dose/ recommended dose and the tumor-type specific efficacy of larotrectinib. In addition, pain status and health-related quality of life of the pediatric patients will be assessed.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumors Harboring NTRK Fusion
Intervention  ICMJE Drug: Larotrectinib (Vitrakvi, BAY2757556)
BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles.
Other Name: LOXO-101
Study Arms  ICMJE
  • Experimental: Phase 1 dose escalation: Dose level 1_Cohort 1
    Intervention: Drug: Larotrectinib (Vitrakvi, BAY2757556)
  • Experimental: Phase 1 dose escalation: Dose level 2_Cohort 2
    Intervention: Drug: Larotrectinib (Vitrakvi, BAY2757556)
  • Experimental: Phase 1 dose escalation: Dose level 3_Cohort 3
    Intervention: Drug: Larotrectinib (Vitrakvi, BAY2757556)
  • Experimental: Phase 2 expansion: Patients with tumors bearing NTRK fusions (IFS)_Cohort 1
    Intervention: Drug: Larotrectinib (Vitrakvi, BAY2757556)
  • Experimental: Phase 2 expansion: Other extra-cranial solid tumors_Cohort 2
    Intervention: Drug: Larotrectinib (Vitrakvi, BAY2757556)
  • Experimental: Phase 2 expansion: Primary CNS tumors_Cohort 3
    Intervention: Drug: Larotrectinib (Vitrakvi, BAY2757556)
  • Experimental: Phase 2 expansion: bone health assessment_sub-cohort
    Intervention: Drug: Larotrectinib (Vitrakvi, BAY2757556)
  • Experimental: Phase 1 dose escalation: Dose expansion
    Intervention: Drug: Larotrectinib (Vitrakvi, BAY2757556)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 7, 2022)
155
Original Estimated Enrollment  ICMJE
 (submitted: December 18, 2015)
36
Estimated Study Completion Date  ICMJE September 22, 2026
Estimated Primary Completion Date July 1, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Phase 1 (Closed):

    • Dose escalation: Birth through 21 years of age at C1D1 with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and for which no standard or available systemic curative therapy exists; OR Infants from birth and older with a diagnosis of malignancy and with a documented NTRK fusion that has progressed or was nonresponsive to available therapies, and for which no standard or available curative therapy exists; OR Patients with locally advanced infantile fibrosarcoma who would require, in the opinion of the investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection. Phase I dose escalation cohorts are closed to enrollment.
    • Dose expansion: In addition to the above stated inclusion criteria, patients must have a malignancy with a documented NTRK gene fusion with the exception of patients with infantile fibrosarcoma, congenital mesoblastic nephroma or secretory breast cancer. Patients with infantile fibrosarcoma, congenital mesoblastic nephroma or secretory breast cancer may enroll into this cohort with documentation of an ETV6 rearrangement by FISH or RT-PCR or a documented NTRK fusion by next generation sequencing.
  • Phase 2:

    • Infants from birth and older at C1D1 with a locally advanced or metastatic infantile fibrosarcoma, patients with locally advanced infantile fibrosarcoma who would require, in the opinion of the investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection; OR Birth through 21 years of age at C1D1 with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and for which no standard or available systemic curative therapy exists with a documented NTRK gene fusion (or in the case of infantile fibrosarcoma, congenital mesoblastic nephroma or secretory breast cancer with documented ETV6 rearrangement (or NTRK3 rearrangement after discussion with the sponsor) by FISH or RT-PCR or a documented NTRK fusion by next generation sequencing) (identified through molecular assays as routinely performed at CLIA or other similarly certified laboratories). Patients with NTRK-fusion positive benign tumors are also eligible; OR Potential patients older than 21 years of age with a tumor diagnosis with histology typical of a pediatric patient and an NTRK fusion may be considered for enrollment following discussion between the local site Investigator and the Sponsor.
  • Patients with primary CNS tumors or cerebral metastasis
  • Karnofsky (those 16 years and older) or Lansky (those younger than 16 years) performance score of at least 50.
  • Adequate hematologic function
  • Adequate hepatic and renal function

Exclusion Criteria:

  • Major surgery within 14 days (2 weeks) prior to C1D1
  • Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to C1D1, ongoing cardiomyopathy; current prolonged QTc interval > 480 milliseconds
  • Active uncontrolled systemic bacterial, viral, or fungal infection
  • Current treatment with a strong CYP3A4 inhibitor or inducer. Enzyme-inducing anti-epileptic drugs (EIAEDs) and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed.
  • Phase 2 only:

    • Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting TRK, including entrectinib, crizotinib and lestaurtinib. Patients who received a TRK inhibitor for less than 28 days of treatment and discontinued because of intolerance remain eligible.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Bayer Clinical Trials Contact (+)1-888-84 22937 clinical-trials-contact@bayer.com
Listed Location Countries  ICMJE Australia,   Canada,   China,   Czechia,   Denmark,   France,   Germany,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Poland,   Russian Federation,   Spain,   Sweden,   Switzerland,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02637687
Other Study ID Numbers  ICMJE 20290
LOXO-TRK-15003 ( Other Identifier: Loxo Oncology, Inc )
2016-003498-16 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description:

Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Current Responsible Party Bayer
Original Responsible Party Loxo Oncology, Inc.
Current Study Sponsor  ICMJE Bayer
Original Study Sponsor  ICMJE Loxo Oncology, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Bayer
Verification Date May 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP