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Trial record 1 of 10 for:    Loxo-292
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A Study of Oral LOXO-292 in Pediatric Patients With Advanced Solid or Primary Central Nervous System Tumors (LIBRETTO-121)

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ClinicalTrials.gov Identifier: NCT03899792
Recruitment Status : Recruiting
First Posted : April 2, 2019
Last Update Posted : October 4, 2019
Sponsor:
Information provided by (Responsible Party):
Loxo Oncology, Inc.

Tracking Information
First Submitted Date  ICMJE February 6, 2019
First Posted Date  ICMJE April 2, 2019
Last Update Posted Date October 4, 2019
Actual Study Start Date  ICMJE July 1, 2019
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 1, 2019)
  • To determine the safety of oral LOXO-292 in pediatric patients with advanced solid tumors: Dose limiting toxicities (DLTs) [ Time Frame: During the first 28-day cycle of LOXO-292 treatment ]
    For Phase 1
  • To determine the safety of oral LOXO-292 in pediatric patients with primary central nervous system (CNS) tumors: Dose limiting toxicities (DLTs) [ Time Frame: During the first 28-day cycle of LOXO-292 treatment ]
    For Phase 1
  • ORR based on RECIST 1.1 per IRC [ Time Frame: Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months) ]
    For Phase 2
  • ORR based on RANO per IRC [ Time Frame: Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months) ]
    For Phase 2
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2019)
  • Plasma concentrations of LOXO-292 [ Time Frame: Days 1 & 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-patient Dose Escalation (each cycle is 28 days) ]
    Phase 1
  • AUC0-24 of LOXO-292 [ Time Frame: Days 1 & 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-patient Dose Escalation (each cycle is 28 days) ]
    Phase 1 & Phase 2
  • Cmax of LOXO-292 [ Time Frame: Days 1 & 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-patient Dose Escalation (each cycle is 28 days) ]
    Phase 1 & Phase 2
  • Tmax of LOXO-292 [ Time Frame: Days 1 & 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-patient Dose Escalation (each cycle is 28 days) ]
    Phase 1 & Phase 2
  • Recommended LOXO-292 Dose for Phase 2 (Maximum Tolerated Dose [MTD]) [ Time Frame: Cycle 1 (28 days) ]
    For Phase 1
  • To assess the preliminary anti-tumor activity of LOXO-292 in pediatric patients with tumors harboring an activating RET alteration as determined by ORR based on RECIST v1.1 [ Time Frame: Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months) ]
    For Phase 1
  • Changes from baseline in pain measures as measured by Wong Baker Faces scales. Wong-Baker Faces Pain Scale includes pictures of facial expressions with correlating scores of 0 being 'no hurt' and 10 being 'hurts worst'. [ Time Frame: Up to 24 months ]
    For Phase 1
  • Changes from baseline in health related quality of life measures as measured by Pediatric Quality of Life Inventory Core. PedsQoL includes a list of problems with scores of 0 being 'never a problem' and 4 being 'almost always a problem'. [ Time Frame: Up to 24 months ]
    For Phase 1
  • Objective Response Rate as assessed by RECIST v1.1, as assessed by investigator [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Objective Response Rate as assessed by RANO, as assessed by investigator [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Duration of response (DOR) as assessed by the Investigator [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Duration of response (DOR) as assessed by the IRC [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Progression free survival (PFS) as assessed by the Investigator [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Progression free survival (PFS) as assessed by the IRC [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Overall survival (OS) [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Clinical Benefit Rate (by Investigator) [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Clinical Benefit Rate (by IRC) [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Frequency of AEs [ Time Frame: From the time of informed consent, for approximately 24 months (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose) ]
    For Phase 2
  • To evaluate the concordance of prior molecular profiling that detected a RET alteration within the subject's tumor with diagnostic tests being evaluated by the Sponsor [ Time Frame: 6 months ]
    For Phase 2
  • Phase 2: Post-operative stage on patients treated with LOXO-292. [ Time Frame: Up to 3 years ]
    Tumor stage is described according to the TNM Classification of malignant tumors of the Union for International Cancer Control (UICC).
  • Phase 2: Surgical margin status in patients treated with LOXO-292. [ Time Frame: Up to 3 years ]
    Tumor margins after surgery are classified into four groups using the International Cancer Control (UICC)-R classification and the Intergroup Rhabdomyosarcoma Staging (IRS) systems: 1) Complete tumor resection with histologically free margins, 2) Macroscopic resection but invaded margins on histology, 3)Macroscopic residual tumor and 4) Distant metastatic tumor.
  • Descriptive analysis of pretreatment surgical plan [ Time Frame: Up to 3 years ]
    For Phase 2
  • Descriptive analysis of post-treatment plans [ Time Frame: Up to 3 years ]
    For Phase 2
Original Secondary Outcome Measures  ICMJE
 (submitted: April 1, 2019)
  • Plasma concentrations of LOXO-292 [ Time Frame: Days 1 & 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-patient Dose Escalation (each cycle is 28 days) ]
    Phase 1
  • AUC0-24 of LOXO-292 [ Time Frame: Days 1 & 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-patient Dose Escalation (each cycle is 28 days) ]
    Phase 1 & Phase 2
  • Cmax of LOXO-292 [ Time Frame: Days 1 & 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-patient Dose Escalation (each cycle is 28 days) ]
    Phase 1 & Phase 2
  • Tmax of LOXO-292 [ Time Frame: Days 1 & 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-patient Dose Escalation (each cycle is 28 days) ]
    Phase 1 & Phase 2
  • Recommended LOXO-292 Dose for Phase 2 (Maximum Tolerated Dose [MTD]) [ Time Frame: Cycle 1 (28 days) ]
    For Phase 1
  • To assess the preliminary anti-tumor activity of LOXO-292 in pediatric patients with tumors harboring an activating RET alteration as determined by ORR based on RECIST v1.1 [ Time Frame: Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months) ]
    For Phase 1
  • Changes from baseline in pain measures as measured by Wong Baker Faces scales. Wong-Baker Faces Pain Scale includes pictures of facial expressions with correlating scores of 0 being 'no hurt' and 10 being 'hurts worst'. [ Time Frame: Up to 24 months ]
    For Phase 1
  • Changes from baseline in health related quality of life measures as measured by Pediatric Quality of Life Inventoy Core. PedsQoL includes a list of problems with scores of 0 being 'never a problem' and 4 being 'almost always a problem'. [ Time Frame: Up to 24 months ]
    For Phase 1
  • Objective Response Rate as assessed by RECIST v1.1, as assessed by investigator [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Objective Response Rate as assessed by RANO, as assessed by investigator [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Duration of response (DOR) as assessed by the Investigator [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Duration of response (DOR) as assessed by the IRC [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Progression free survival (PFS) as assessed by the Investigator [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Progression free survival (PFS) as assessed by the IRC [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Overall survival (OS) [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Clinical Benefit Rate (by Investigator) [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Clinical Benefit Rate (by IRC) [ Time Frame: Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in patients who have not progressed. ]
    For Phase 2
  • Frequency of AEs [ Time Frame: From the time of informed consent, for approximately 24 months (or earlier if the patient discontinues from the study), and through Safety Follow-up (28 days after the last dose) ]
    For Phase 2
  • To evaluate the concordance of prior molecular profiling that detected a RET alteration within the subject's tumor with diagnostic tests being evaluated by the Sponsor [ Time Frame: 6 months ]
    For Phase 2
  • Phase 2: Post-operative stage on patients treated with LOXO-292. [ Time Frame: Up to 3 years ]
    Tumor stage is described according to the TNM Classification of malignant tumors of the Union for International Cancer Control (UICC).
  • Phase 2: Surgical margin status in patients treated with LOXO-292. [ Time Frame: Up to 3 years ]
    Tumor margins after surgery are classified into four groups using the International Cancer Control (UICC)-R classification and the Intergroup Rhapdomyosarcoma Staging (IRS) systems: 1) Complete tumor resection with histologically free margins, 2) Macroscopic resection but invaded margins on histology, 3)Macroscropic residual tumor and 4) Distant metastatic tumor.
  • Descriptive analysis of pretreatment surgical plan [ Time Frame: Up to 3 years ]
    For Phase 2
  • TDescriptive analysis of post-treatment plans [ Time Frame: Up to 3 years ]
    For Phase 2
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Oral LOXO-292 in Pediatric Patients With Advanced Solid or Primary Central Nervous System Tumors
Official Title  ICMJE A Phase 1/2 Study of the Oral RET Inhibitor LOXO 292 in Pediatric Patients With Advanced RET-Altered Solid or Primary Central Nervous System Tumors
Brief Summary This is an open-label, multi-center Phase 1/2 study of oral LOXO-292 in pediatric patients with an activating RET alteration and an advanced solid or primary CNS tumor.
Detailed Description This study includes 2 parts: phase 1 (dose escalation) and phase 2 (dose expansion). In phase 1, patients will be enrolled using a rolling 6 dose escalation scheme. The starting dose of LOXO-292 is equivalent to the adult recommended phase 2 dose of 160mg BID. Once the MTD and/or RP2D is identified, patients will be enrolled to one of four phase 2 dose expansion cohorts depending on tumor histology and tumor genotype. Cycle length will be 28 days.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Medullary Thyroid Cancer
  • Infantile Myofibromatosis
  • Infantile Fibrosarcoma
  • Papillary Thyroid Cancer
  • Soft Tissue Sarcoma
Intervention  ICMJE Drug: LOXO-292
Oral LOXO-292
Study Arms  ICMJE Experimental: LOXO-292
Phase 1- Dose Escalation and determination of MTD; multiple dose levels of LOXO-292 to be evaluated; Phase 2 - The maximum tolerated dose (MTD)/recommended dose from Phase 1
Intervention: Drug: LOXO-292
Publications * Not Provided

*   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 1, 2019)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2022
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Advanced or metastatic solid or primary CNS tumor which has failed standard of care therapies
  • Evidence of an activating RET gene alteration in the tumor and/ or blood
  • Measurable or non-measurable disease
  • Karnofsky (patients 16 years and older) or Lansky (patients younger than 16) performance score of at least 50.
  • Patient with primary CNS tumors or cerebral metastases must be neurologically stable for 7 days prior and must not have required increasing doses of steroids within the last 7 days.
  • Adequate hematologic, hepatic and renal function.
  • Ability to receive study drug therapy orally or via gastric access
  • Willingness of men and women of reproductive potential to observe conventional and effective birth control

Exclusion Criteria:

  • Major surgery within 4 weeks prior to planned start of LOXO-292.
  • Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292.
  • Active uncontrolled systemic bacterial, viral, fungal or parasitic infection.
  • Clinically significant active malabsorption syndrome.
  • Pregnancy or lactation
  • Uncontrolled symptomatic hyperthyroidism or hypothyroidism (i.e. the patient required a modification to current thyroid medication in the 7 days before start of LOXO-292).
  • Uncontrolled symptomatic hypercalcemia or hypocalcemia.
  • Current treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers.
  • Known hypersensitivity to any of the components of the investigational agent, LOXO-292 or Ora-Sweet® SF and OraPlus®, for patients who will receive LOXO-292 suspension.
  • Current treatment with proton pump inhibitors.
  • Prior treatment with a selective RET inhibitor(s) (including investigational selective RET inhibitor[s]).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Patient Advocacy 855-RET-4-292 (855-738-4292) clinicaltrials@loxooncology.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03899792
Other Study ID Numbers  ICMJE LOXO-RET-18036
2019‐000212‐28 ( 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 Not Provided
Responsible Party Loxo Oncology, Inc.
Study Sponsor  ICMJE Loxo Oncology, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Elizabeth Olek, DO, MPH Loxo Oncology
PRS Account Loxo Oncology, Inc.
Verification Date October 2019

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