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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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).

Detailed 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).

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.


Sponsor: Loxo Oncology, Inc.

Current Primary Outcome: 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)



Original Primary Outcome: 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 ]

Current Secondary Outcome:

  • 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 punitive pretreatment surgical plan and capture the post treatment actual approach with an emphasis on the functional and cosmetic outcome [ Time Frame: 6 Months ]


Original Secondary Outcome:

  • 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 ]


Information By: Loxo Oncology, Inc.

Dates:
Date Received: December 10, 2015
Date Started: December 2015
Date Completion: December 2017
Last Updated: April 12, 2017
Last Verified: April 2017