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Trial record 3 of 4 for:    loxo-101

Study of LOXO-101 in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by Loxo Oncology, Inc.
Sponsor:
Information provided by (Responsible Party):
Loxo Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT02576431
First received: October 12, 2015
Last updated: November 16, 2016
Last verified: November 2016
  Purpose
Phase II, multi-center, open-label study of patients with advanced solid tumors harboring a fusion of NTRK1, NTRK2 or NTRK3.

Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Thyroid Neoplasms
Sarcoma
Colorectal Neoplasms
Salivary Gland Neoplasms
Biliary Tract Neoplasms
Brain Neoplasm, Primary
Carcinoma, Ductal, Breast
Melanoma
Solid Tumors
Glioblastoma
Bile Duct Neoplasms
Astrocytoma
Head and Neck Squamous Cell Carcinoma
Pontine Glioma
Drug: LOXO-101
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Basket Study of the Oral TRK Inhibitor LOXO-101 in Subjects With NTRK Fusion-Positive Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Best Overall Response of confirmed CR or PR as measured by RECIST 1.1 or RANO criteria as appropriate to tumor type [ Time Frame: Up to 30 Months ]

Secondary Outcome Measures:
  • Duration of Response (DOR) [ Time Frame: Up to 30 months ]
  • Progression Free Survival (PFS) [ Time Frame: Up to 30 months ]
  • Overall Survival (OS) [ Time Frame: Through study completion up to 42 months ]
    Number of months from the initiation of LOXO-101 to the date of death due to any cause.

  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Up to 30 months ]
    To assess the safety profile and tolerability of LOXO-101


Estimated Enrollment: 151
Study Start Date: October 2015
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Non Small Cell Lung Cancer
Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral LOXO-101
Drug: LOXO-101
Oral capsule of LOXO-101 - 100mg BID
Thyroid
Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral LOXO-101
Drug: LOXO-101
Oral capsule of LOXO-101 - 100mg BID
Sarcoma
Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral LOXO-101
Drug: LOXO-101
Oral capsule of LOXO-101 - 100mg BID
Colorectal
Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral LOXO-101
Drug: LOXO-101
Oral capsule of LOXO-101 - 100mg BID
Salivary
Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral LOXO-101
Drug: LOXO-101
Oral capsule of LOXO-101 - 100mg BID
Biliary
Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral LOXO-101
Drug: LOXO-101
Oral capsule of LOXO-101 - 100mg BID
Primary CNS
Brain Tumor Measurable by RANO Oral LOXO-101
Drug: LOXO-101
Oral capsule of LOXO-101 - 100mg BID
All Other Solid Tumors
Tumor Histology not in Cohorts 1-7 Evaluable but not Measurable Disease Oral LOXO-101
Drug: LOXO-101
Oral capsule of LOXO-101 - 100mg BID

Detailed Description:

This is a Phase II, multi-center, open-label study of patients with advanced solid tumors harboring a fusion of NTRK1, NTRK2 or NTRK3. Patients with NTRK1, NTRK2 or NTRK3 fusion-positive cancers will be identified through molecular assay.

LOXO-101 will be administered at 100mg twice daily (BID), with each cycle consisting of 28 days of dosing administered on a continuous basis.

The study will include 8 cohorts of patients with tumors bearing NTRK fusions, including non small cell lung cancer, thyroid cancer, sarcoma, colorectal cancer, salivary gland cancer, biliary cancer and primary CNS tumor, as well as a cohort that will enroll patients not included in the histologies listed above.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Locally-advanced or metastatic malignancy with an NTRK1, NTRK2 or NTRK3 gene fusion, identified through molecular assays as routinely performed at CLIA or other similarly-certified laboratories.
  2. Subjects must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy.
  3. Subjects must have at least one measurable lesion as defined by RECIST 1.1 (Eisenhauer 2009). Subjects without RECIST measurable disease (e.g., evaluable disease only) will be eligible for enrollment to Cohort 8, regardless of tumor type. Subjects in Cohort 7 (primary CNS tumors) should meet the following criteria:

    • Have received prior treatment including radiation and/or chemotherapy, with radiation completed > 12 weeks prior to C1D1 of therapy.
    • Have ≥ 1 site of bi-dimensionally measurable disease (confirmed by magnetic resonance imaging [MRI] and evaluable by RANO criteria), with the size of at least one of the measurable lesions ≥ 1 cm in each dimension and noted on more than one imaging slice.
    • Imaging study performed within 28 days before enrollment while on stable dose steroid medication for at least 5 days immediately before and during the imaging study.
  4. Adequate organ function as defined by the following criteria:

    • Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) < 2.5 upper limit of normal (ULN), or AST and ALT < 5 ULN if liver function abnormalities are due to underlying malignancy.
    • Total bilirubin < 2.0 ULN. Subjects with a known history of Gilberts Disease and an isolated elevation of indirect bilirubin are eligible.
    • Serum creatinine < 2.0 ULN OR an estimated glomerular filtration rate ≥ 30 mL/minute using the Cockroft-Gault formula.
  5. Ability to swallow capsules,

Key Exclusion Criteria:

  1. Symptomatic or unstable brain metastases. (Note: Subjects with asymptomatic brain metastases are eligible to participate in the study). Subjects with primary CNS tumors are eligible.
  2. Pregnancy or lactation.
  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: NCT02576431

Contacts
Contact: Maegan Deegan 1-855-NTRK-123 maegan@loxooncology.com
Contact: Lia Donahue 1-855-NTRK-123 lia@loxooncology.com

  Show 26 Study Locations
Sponsors and Collaborators
Loxo Oncology, Inc.
Investigators
Study Director: Nora Ku, MD Loxo Oncology
  More Information

Responsible Party: Loxo Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02576431     History of Changes
Other Study ID Numbers: LOXO-TRK-15002 
Study First Received: October 12, 2015
Last Updated: November 16, 2016

Keywords provided by Loxo Oncology, Inc.:
LOXO-101
NTRK Fusion Positive
Loxo
TRK
TRK Fusion
NTRK1
NTRK2
NTRK3
TRKA
TRKB
TRKC
ETV6
NTRK

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Neoplasms
Glioblastoma
Astrocytoma
Head and Neck Neoplasms
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Brain Neoplasms
Thyroid Neoplasms
Biliary Tract Neoplasms
Bile Duct Neoplasms
Carcinoma, Ductal, Breast
Salivary Gland Neoplasms
Carcinoma, Ductal
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neoplasms by Site
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases

ClinicalTrials.gov processed this record on February 24, 2017