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Oral TRK Inhibitor LOXO-101 (Larotrectinib) for Treatment of Advanced Pediatric Solid or Primary Central Nervous System Tumors (SCOUT)

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by Loxo Oncology, Inc.
Sponsor:
Information provided by (Responsible Party):
Loxo Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT02637687
First received: December 10, 2015
Last updated: August 8, 2017
Last verified: August 2017
  Purpose
This is a multicenter, open label, Phase 1/2 study in pediatric patients with advanced solid or primary CNS tumors. LOXO‑101 (larotrectinib) will be administered orally (PO) twice daily (BID), with the dose adjusted by body surface area (BSA).

Condition Intervention Phase
Neoplasms Central Nervous System Neoplasms Drug: LOXO-101 (larotrectinib) Phase 1 Phase 2

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of the Oral TRK Inhibitor LOXO101 (Larotrectinib) in Pediatric Patients With Advanced Solid or Primary Central Nervous System Tumors

Resource links provided by NLM:


Further study details as provided by Loxo Oncology, Inc.:

Primary Outcome Measures:
  • Phase 1: To determine the safety of oral LOXO-101 (larotrectinib) in pediatric patients with advanced solid or primary central nervous system (CNS) tumors. Phase 2: To determine the overall response rate (ORR). [ Time Frame: 6 Months ]

    Phase 1: To determine the safety of oral LOXO-101 (larotrectinib), including dose-limiting toxicity (DLT), in pediatric patients with advanced solid or primary central nervous system (CNS) tumors.

    Phase 2: To determine the overall response rate (ORR) as determined by an independent radiology review committee and measured by the proportion of subjects with best overall confirmed response of complete response (CR) or partial response (PR) by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), or Response Assessment in Neuro-Oncology (RANO) criteria, as appropriate, following treatment with LOXO-101 (larotrectinib) in pediatric subjects with an advanced cancer harboring a fusion involving NTRK1, NTRK2, or NTRK3 (collective referred to as neurotrophic tyrosine kinase receptor [NTRK] fusions)



Secondary Outcome Measures:
  • To characterize the pharmacokinetic (PK) properties of LOXO-101 (larotrectinib) in pediatric patients with advanced solid or primary CNS tumors [ Time Frame: 6 Months ]
  • To identify the recommended maximum tolerated dose and/or the appropriate dose of LOXO‑101 (larotrectinib) for further clinical investigation in this patient population [ Time Frame: 6 Months ]
  • To describe the antitumor activity of LOXO-101 (larotrectinib) in pediatric patients with advanced solid or primary CNS tumors [ Time Frame: 6 Months ]
  • To describe pain and health related quality of life (HRQOL) in pediatric patients with advanced solid or primary CNS tumors treated with LOXO-101 (larotrectinib) [ Time Frame: 6 Months ]
  • To assess the safety profile and tolerability of LOXO-101 (larotrectinib) [ Time Frame: 6 Months ]
  • To evaluate the concordance of prior molecular profiling that detected an NTRK fusion within the subject's tumor with diagnostic tests being evaluated by the Sponsor [ Time Frame: 6 Months ]
  • To characterize post-operative staging and surgical margin status in patients who have definitive surgery following treatment with LOXO-101 (larotrectinib) [ Time Frame: 6 Months ]
  • To describe the putitive pretreatment surgical plan and capture the post treatment actual approach with an emphasis on the functional and cosmetic outcome [ Time Frame: 6 Months ]

Estimated Enrollment: 84
Study Start Date: December 2015
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Open Label LOXO-101 (larotrectinib)
Drug: LOXO-101 (larotrectinib)
Capsules / Liquid Administration

Detailed Description:

This is a multicenter, open label, Phase 1/2 study in pediatric patients with advanced solid or primary CNS tumors. LOXO‑101 (larotrectinib) will be administered orally (PO) twice daily (BID), with the dose adjusted by body surface area (BSA).

Dose Escalation Phase will proceed through the planned 4 dose levels, or until the MTD is reached, or until the Sponsor determines that a suitable dose has been achieved based on PK exposure..

Expansion Cohorts may be enrolled to better characterize safety and efficacy in patients with specific abnormalities in the NTRK genes or proteins.

  Eligibility

Ages Eligible for Study:   1 Month to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pediatric patients ≥ 1 year old on Cycle 1 Day 1 (C1D1)
  • Phase 1 only: Between 1 and 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, or ≥1 month old with a diagnosis 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 2 only: Ages >/= 1 month of age 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 enrollment or ages 1 month 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 with a documented NTRK gene fusion (identified through molecular assays as routinely performed at CLIA or other similarly-certified laboratories) or (including Expansion Phase) 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's Medical Monitor.
  • Karnofsky (those 16 years old or older) or Lansky (those younger than 16 years) performance score of at least 50
  • Adequate hematologic function: Absolute neutrophil count (ANC) ≥ 1.0 109/L, platelet count ≥ 100.0 109/L and hemoglobin ≥ 8.0 g/dL (patients with bone marrow involvement will not be evaluable for hematologic DLT and can enroll with ANC ≥ 0.75 109/L, platelet count ≥ 50.0 109/L and hemoglobin ≥ 8.0 g/dL)
  • Adequate hepatic function: Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 upper limit of normal (ULN) for age (patients with documented Gilbert's Disease may be enrolled with Sponsor approval).
  • Adequate renal function: Estimated glomerular filtration rate ≥ 30 mL/minute using the Cockroft-Gault formula or: a serum creatinine based on age/gender as outlined in the protocol

Exclusion Criteria:

  • Investigational agent, anticancer therapy, or major surgery within 14 days (2 weeks) prior to C1D1
  • Clinically significant active cardiovascular disease or history of prolonged QT interval corrected for heart rate (QTc)
  • Current treatment with a strong cytochrome P450 (CYP) 3A4 inhibitor or inducer (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 lestaurtanib. Patients who received a TRK inhibitor for less than 28 days of treatment and discontinued because of intolerance remain eligible.
  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: NCT02637687

Contacts
Contact: Patient Advocacy 1-855-NTRK-123 clinicaltrials@loxooncology.com

Locations
United States, California
Childrens Hospital of Los Angeles Recruiting
Los Angeles, California, United States, 90027
UCLA Jonsson Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90095
Lucile Packard Children's Hospital, Stanford University Recruiting
Palo Alto, California, United States, 94304
United States, Florida
Nemours Children's Hospital Recruiting
Orlando, Florida, United States, 32827
United States, Massachusetts
Boston Children's/Dana Farber Institute Recruiting
Boston, Massachusetts, United States, 02115
United States, New York
Memorial Sloan Kettering Center Center Recruiting
New York, New York, United States, 10065
United States, Ohio
Cincinnati Childrens Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
United States, Tennessee
St. Jude's Childrens Hospital Recruiting
Memphis, Tennessee, United States, 38105
United States, Texas
University of Texas Southwestern Medical Center/Children's Medical Center Recruiting
Dallas, Texas, United States, 75235
United States, Washington
Children's Hospital and Medical Center Recruiting
Seattle, Washington, United States, 98105
France
Institut Curie - Oncologie Medicale Recruiting
Paris, France, 75005
Institut Gustave Roussy Recruiting
Villejuif, France, 94800
Germany
Universitaetsklinikum Heidelberg - Zentrum fuer Kinder- und Jugendmedizin ZIPO Recruiting
Heidelberg, Germany, 69120
Olgahospital Recruiting
Stuttgart, Germany, 70174
Italy
Fondazione IRCCS Istituto Nazionale dei Tumori Recruiting
Milano, Italy, 20133
Spain
Hospital Universitario Vall d'Hebron Recruiting
Barcelona, Spain, 8035
Sponsors and Collaborators
Loxo Oncology, Inc.
Investigators
Study Director: Michael Cox, PharmD, MHSc, BCOP Loxo Oncology
  More Information

Responsible Party: Loxo Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02637687     History of Changes
Other Study ID Numbers: LOXO-TRK-15003
Study First Received: December 10, 2015
Last Updated: August 8, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Loxo Oncology, Inc.:
Pediatric
NTRK1
NTRK2
NTRK3
Fusion
Tumors
Solid Tumors
CNS Tumors
Central Nervous System Tumors
NTRK Fusion Positive
TRKA
TRKB
TRKC
Infantile Fibrosarcoma
NTRK Gene Rearrangements
TRK Fusion
NTRK1 fusion
NTRK2 fusion
NTRK3 fusion
NTRK1 gene rearrangement
NTRK2 gene rearrangement
NTRK3 gene rearrangement
ETV6-NTRK3
ETV6
ETV6 fusion
ETV6 gene rearrangement
Solid CNS tumor
Primary CNS tumor
Advanced CNS tumor
Metastatic CNS tumor

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

ClinicalTrials.gov processed this record on September 19, 2017