Clinical Trials /

A Study of Oral LOXO-292 in Pediatric Patients With Advanced Solid or Primary Central Nervous System Tumors

NCT03899792

Description:

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.

Related Conditions:
  • Malignant Central Nervous System Neoplasm
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Oral LOXO-292 in Pediatric Patients With Advanced Solid or Primary Central Nervous System Tumors
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: LOXO-RET-18036
  • SECONDARY ID: 2019‐000212‐28
  • NCT ID: NCT03899792

Conditions

  • Medullary Thyroid Cancer
  • Infantile Myofibromatosis
  • Infantile Fibrosarcoma
  • Papillary Thyroid Cancer
  • Soft Tissue Sarcoma

Interventions

DrugSynonymsArms
LOXO-292LOXO-292

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
LOXO-292ExperimentalPhase 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
  • LOXO-292

Eligibility Criteria

        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 evaluable 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 14 days 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 prior to first dose of
             study treatment)."

          -  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.
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:6 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:For Phase 1

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:Phase 1
Measure: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)
Safety Issue:
Description:Phase 1 & Phase 2
Measure: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)
Safety Issue:
Description:Phase 1 & Phase 2
Measure: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)
Safety Issue:
Description:Phase 1 & Phase 2
Measure:Recommended LOXO-292 Dose for Phase 2 (Maximum Tolerated Dose [MTD])
Time Frame:Cycle 1 (28 days)
Safety Issue:
Description:For Phase 1
Measure: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)
Safety Issue:
Description:For Phase 1
Measure: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
Safety Issue:
Description:For Phase 1
Measure: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
Safety Issue:
Description:For Phase 1
Measure: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.
Safety Issue:
Description:For Phase 2
Measure: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.
Safety Issue:
Description:For Phase 2
Measure: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.
Safety Issue:
Description:For Phase 2
Measure: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.
Safety Issue:
Description:For Phase 2
Measure: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.
Safety Issue:
Description:For Phase 2
Measure: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.
Safety Issue:
Description:For Phase 2
Measure: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.
Safety Issue:
Description:For Phase 2
Measure: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.
Safety Issue:
Description:For Phase 2
Measure: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.
Safety Issue:
Description:For Phase 2
Measure: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)
Safety Issue:
Description:For Phase 2
Measure: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
Safety Issue:
Description:For Phase 2
Measure:Phase 2: Post-operative stage on patients treated with LOXO-292.
Time Frame:Up to 3 years
Safety Issue:
Description:Tumor stage is described according to the TNM Classification of malignant tumors of the Union for International Cancer Control (UICC).
Measure:Phase 2: Surgical margin status in patients treated with LOXO-292.
Time Frame:Up to 3 years
Safety Issue:
Description: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.
Measure:Descriptive analysis of pretreatment surgical plan
Time Frame:Up to 3 years
Safety Issue:
Description:For Phase 2
Measure:TDescriptive analysis of post-treatment plans
Time Frame:Up to 3 years
Safety Issue:
Description:For Phase 2

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Loxo Oncology, Inc.

Trial Keywords

  • Loxo
  • LOXO-292
  • KIF5B-RET
  • M918T
  • CCDC6-RET
  • RET-PTC1
  • NCOA4-RET
  • RET-PTC
  • RET-PTC3
  • RET-PTC4
  • PRKAR1A-RET
  • RET-PTC2
  • GOLGA5-RET
  • RET-PTC5
  • ERC1-RET
  • KTN1-RET
  • RET-PTC8
  • HOOK3-RET
  • PCM1-RET
  • TRIM24-RET
  • RET-PTC6
  • TRIM27-RET
  • TRIM33-RET
  • RET-PTC7
  • AKAP13-RET
  • FKBP15-RET
  • SPECC1L-RET
  • TBL1XR1-RET
  • BCR-RET
  • FGRF1OP-RET
  • RFG8-RET
  • RET-PTC9
  • ACBD5-RET
  • MYH13-RET
  • CUX1-RET
  • KIAA1468-RET
  • FRMD4A-RET
  • SQSTM1-RET
  • AFAP1L2-RET
  • PPFIBP2-RET
  • EML4-RET
  • PARD3-RET
  • G533C
  • C609F
  • C609G
  • C609R
  • C609S
  • C609Y
  • C611F
  • C611G
  • C611S
  • C611Y
  • C611W
  • C618F
  • C618R
  • C618S
  • C620F
  • C620R
  • C620S
  • C630R
  • C630Y
  • D631Y
  • C634F
  • C634G
  • C634R
  • C634S
  • C634W
  • C634Y
  • K666E
  • E768D
  • L790F
  • V804L
  • V804M
  • A883F
  • S891A
  • R912P
  • CLIP1-RET
  • Y806C
  • RET fusion
  • RET alteration
  • RET mutation
  • RET rearrangement
  • RET translocation
  • Neoplasms by Site
  • Neoplasms
  • Non-Small Cell Lung Cancer
  • Lung Neoplasms
  • Carcinoma, Non-Small-Cell Lung
  • Cancer of Lung
  • Cancer of the Lung
  • Lung Cancer
  • Neoplasms, Lung
  • Neoplasms, Pulmonary
  • Pulmonary Cancer
  • Pulmonary Neoplasms
  • Respiratory Tract Neoplasms
  • Lung Diseases
  • Respiratory Tract Diseases
  • Carcinoma, Bronchogenic
  • Bronchial Neoplasms
  • Medullary Thyroid Cancer
  • Papillary Thyroid Cancer
  • Thyroid Diseases
  • Thyroid Neoplasms
  • Cancer of the Thyroid
  • Cancer of Thyroid
  • Neoplasms, Thyroid
  • Thyroid Adenoma
  • Thyroid Cancer
  • Thyroid Carcinoma
  • Endocrine System Diseases
  • Endocrine Gland Neoplasms
  • Head and Neck Neoplasms
  • Thoracic Neoplasms
  • CNS tumor
  • Primary CNS tumor
  • Colonic Neoplasms
  • Cancer of Colon
  • Cancer of the Colon
  • Colon Cancer
  • Colon Neoplasms
  • Colonic Cancer
  • Neoplasms, Colonic
  • Malignant tumor of Breast
  • Mammary Cancer
  • Mammary Carcinoma, Human
  • Mammary Neoplasm, Human
  • Neoplasms, Breast
  • Tumors, Breast
  • Human Mammary Carcinoma
  • Malignant Neoplasm of Breast
  • Breast Carcinoma
  • Breast Tumors
  • Cancer of the Breast
  • Breast Neoplasms
  • Breast Cancer
  • RET Inhibitor
  • MTC
  • NSCLC
  • Soft tissue sarcoma
  • Infantile Myofibromatosis
  • Infantile Fibrosarcoma

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