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

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ClinicalTrials.gov Identifier: NCT02637687
Recruitment Status : Recruiting
First Posted : December 22, 2015
Last Update Posted : July 27, 2018
Sponsor:
Information provided by (Responsible Party):
Loxo Oncology, Inc.

Brief Summary:
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 or disease Intervention/treatment Phase
Neoplasms Central Nervous System Neoplasms Drug: LOXO-101 (larotrectinib) Phase 1 Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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 has completed enrollment and it has been determined that the maximum dose for the Phase 1 Expansion and Phase 2 portions of the study will be no higher than the recommended Phase 2 dose of 100 mg BID in the adult Phase 2 trial, regardless of the patient's BSA.

Phase 1 Expansion and Phase 2 portions of the study are currently enrolling.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 92 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of the Oral TRK Inhibitor LOXO-101 (Larotrectinib) in Pediatric Patients With Advanced Solid or Primary Central Nervous System Tumors
Actual Study Start Date : December 2015
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment
Open Label LOXO-101 (larotrectinib)
Drug: LOXO-101 (larotrectinib)
Capsules / Liquid Administration




Primary Outcome Measures :
  1. 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 :
  1. To characterize the pharmacokinetic (PK) properties of LOXO-101 (larotrectinib) in pediatric patients with advanced solid or primary CNS tumors [ Time Frame: 6 Months ]
  2. 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 ]
  3. To describe the antitumor activity of LOXO-101 (larotrectinib) in pediatric patients with advanced solid or primary CNS tumors [ Time Frame: 6 Months ]
  4. 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 ]
  5. To assess the safety profile and tolerability of LOXO-101 (larotrectinib) [ Time Frame: 6 Months ]
  6. 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 ]
  7. 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 ]
  8. 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 ]


Information from the National Library of Medicine

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

Inclusion Criteria:

  • Pediatric patients ≥ 1 day old on Cycle 1 Day 1 (C1D1)
  • Phase 1: 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. The Phase I dose escalation cohorts are closed to enrollment. In addition to the above stated Inclusion Criteria, patients eligible for enrollment into this cohort 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 NGS.
  • Phase 2 only: 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 medoblastic nephroma or secretory breast cancer with documented ETV6 rearrangement by FISH or RT-PCR or a documented NTRK fusion by NGS) (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. Patients with NTRK-fusion positive benign tumors are also eligible.
  • 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) ≤ 2.5 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.

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): NCT02637687


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

  Show 22 Study Locations
Sponsors and Collaborators
Loxo Oncology, Inc.
Investigators
Study Director: Michael Cox, PharmD, MHSc, BCOP Loxo Oncology

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Loxo Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02637687     History of Changes
Other Study ID Numbers: LOXO-TRK-15003
First Posted: December 22, 2015    Key Record Dates
Last Update Posted: July 27, 2018
Last Verified: July 2018
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