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Trial record 3 of 7 for:    loxo-101

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

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ClinicalTrials.gov Identifier: NCT02576431
Recruitment Status : Recruiting
First Posted : October 15, 2015
Last Update Posted : September 5, 2018
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Loxo Oncology, Inc.

Brief Summary:
Phase II, multi-center, open-label study of patients with advanced solid tumors harboring a fusion of NTRK1, NTRK2 or NTRK3.

Condition or disease Intervention/treatment 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 Pancreatic Neoplasms Ovarian Neoplasms Carcinoma, Renal Cell Cholangiocarcinoma Carcinoma Carcinoma, Bronchogenic Bronchial Neoplasms Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms, Nerve Tissue Nevi and Melanomas Drug: Larotrectinib LOXO-101 Phase 2

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

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.

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

The study will analyze 9 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. Cohort 9 will include patients who meet criteria for Cohorts 1 to 8, but with documented NTRK fusion from a laboratory where CLIA or equivalent certification cannot be confirmed by the Sponsor at the time of consent.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 176 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Basket Study of the Oral TRK Inhibitor LOXO-101 (Larotrectinib) in Subjects With NTRK Fusion-Positive Tumors
Study Start Date : October 2015
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Non Small Cell Lung Cancer
Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral larotrectinib (LOXO-101)
Drug: Larotrectinib LOXO-101
Oral capsule of larotrectinib (LOXO-101) - 100mg BID

Thyroid
Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral larotrectinib (LOXO-101)
Drug: Larotrectinib LOXO-101
Oral capsule of larotrectinib (LOXO-101) - 100mg BID

Sarcoma
Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral larotrectinib (LOXO-101)
Drug: Larotrectinib LOXO-101
Oral capsule of larotrectinib (LOXO-101) - 100mg BID

Colorectal
Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral larotrectinib (LOXO-101)
Drug: Larotrectinib LOXO-101
Oral capsule of larotrectinib (LOXO-101) - 100mg BID

Salivary
Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral larotrectinib (LOXO-101)
Drug: Larotrectinib LOXO-101
Oral capsule of larotrectinib (LOXO-101) - 100mg BID

Biliary
Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral larotrectinib (LOXO-101)
Drug: Larotrectinib LOXO-101
Oral capsule of larotrectinib (LOXO-101) - 100mg BID

Primary CNS
Brain Tumor Measurable by RANO Oral larotrectinib (LOXO-101)
Drug: Larotrectinib LOXO-101
Oral capsule of larotrectinib (LOXO-101) - 100mg BID

All Other Solid Tumors
Tumor Histology not in Cohorts 1-7 Evaluable but not Measurable Disease Oral larotrectinib (LOXO-101)
Drug: Larotrectinib LOXO-101
Oral capsule of larotrectinib (LOXO-101) - 100mg BID

Eligible for cohorts 1-8 but lab certification not confirmed
Subjects eligible for Cohorts 1-8, but lab CLIA- or equivalent certification cannot be confirmed at time of Subjects eligible for Cohorts 1-8, but lab CLIA- or equivalent certification cannot be confirmed at time of consent Oral larotrectinib (LOXO-101)
Drug: Larotrectinib LOXO-101
Oral capsule of larotrectinib (LOXO-101) - 100mg BID




Primary Outcome Measures :
  1. Overall Response Rate 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 RECISTv1.1 or RANO criteria [ Time Frame: Up to 30 Months ]

Secondary Outcome Measures :
  1. Overall Response Rate of confirmed CR or PR as determined by the treating investigator Overall Response Rate based on the treating Investigator's response assessment using RECISTv1.1 or RANO criteria, as appropriate to tumor type. [ Time Frame: Up to 30 months ]
  2. Duration of response for subjects with best overall response of confirmed CR or PR by Independent Radiology Committee [ Time Frame: Up to 30 months ]
  3. Duration of response for subjects with best overall response of confirmed CR or PR by the treating investigator [ Time Frame: Up to 30 months ]
  4. To estimate the proportion of subjects that has any tumor regression as a best response. [ Time Frame: Up to 30 months ]
  5. Duration of Progression Free Survival following initiation of larotrectinib (LOXO-101) [ Time Frame: Up to 30 months ]
    Number of months from initiation of larotrectinib (LOXO-101) to the earlier of disease progression or death due to any cause.

  6. Duration of overall survival (OS) following initiation of larotrectinib (LOXO-101) [ Time Frame: Through study completion up to 42 months ]
    Number of months from the initiation of larotrectinib (LOXO-101) to the date of death due to any cause.

  7. To assess the safety profile and tolerability of larotrectinib (LOXO-101). [ Time Frame: Through study completion up to 42 months ]
    Incidence, duration, and severity of adverse events

  8. Comparison of Progression Free Survival following initiation of larotrectinib (LOXO-101) to that following the line of therapy immediately preceding larotrectinib (LOXO-101) in each subject who has received prior therapy. [ Time Frame: Up to 30 months ]
    Number of months from initiation of larotrectinib (LOXO-101) to the earlier of disease progression or death due to any cause

  9. Evaluate the clinical benefit rate (CBR) based on the proportion of subjects with best overall response of CR, PR, or stable disease lasting 16 or more weeks following initiation of larotrectinib (LOXO-101) [ Time Frame: Up to 30 months ]
  10. "Evaluate the concordance of prior molecular profiling that detected an NTRK fusion within the subject's tumor with the diagnostic test being evaluated by the Sponsor" [ Time Frame: Up to 30 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
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. Subjects who have NTRK gene fusion identified in a lab where certification of the lab cannot be confirmed by the Sponsor at the time of consent may enroll to Cohort 9.
  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. 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 < 2.5 x ULN, except in the setting of biliary obstruction. Subjects with a known history of Gilberts Disease and an isolated elevation of indirect bilirubin are eligible
    • Serum creatinine < 2.0 x ULN OR an estimated glomerular filtration rate ≥ 30 mL/minute using the Cockcroft-Gault formula
    • ECOG score < 3 (age >16 years) or Lansky Performance Score (LPS) >40% (age <16 years). If enrolled with primary CNS tumor to be assessed by RANO, Karnofsky Performance Score (KPS) (age >16 years) or LPS (age <16 years) >50%
    • Archived tumor tissue. If archival tissue is known to not be available, then an on-study tumor biopsy should be attempted if it can be safely performed.

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. Investigational agent or anticancer therapy within 2 weeks prior to the planned start of larotrectinib (LOXO-101) or 5 half-lives, whichever is shorter, and without recovery of clinically significant toxicities from that therapy.
  3. Pregnancy or lactation.

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): NCT02576431


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

  Show 35 Study Locations
Sponsors and Collaborators
Loxo Oncology, Inc.
Bayer
Investigators
Study Director: Nora Ku, MD Loxo Oncology

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Loxo Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02576431     History of Changes
Other Study ID Numbers: LOXO-TRK-15002
First Posted: October 15, 2015    Key Record Dates
Last Update Posted: September 5, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Loxo Oncology, Inc.:
LOXO-101
NTRK Fusion Positive
Loxo
TRK
TRK Fusion
NTRK1
NTRK2
NTRK3
TRKA
TRKB
TRKC
ETV6
NTRK
larotrectinib
fusion
tumors
CNS tumors
solid tumors
central nervous system tumors
solid CNS tumors
primary CNS tumor
Advanced CNS tumor
Metastatic CNS tumor
NTRK1 fusion
NTRK2 fusion
NTRK3 fusion
ETV6-NTRK3
ETV6 fusion

Additional relevant MeSH terms:
Carcinoma
Neoplasms
Melanoma
Carcinoma, Squamous Cell
Glioblastoma
Astrocytoma
Cholangiocarcinoma
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Head and Neck Neoplasms
Lung Neoplasms
Pancreatic Neoplasms
Ovarian Neoplasms
Brain Neoplasms
Carcinoma, Renal Cell
Thyroid Neoplasms
Biliary Tract Neoplasms
Thoracic Neoplasms
Respiratory Tract Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carcinoma, Ductal
Bile Duct Neoplasms
Neoplasms, Nerve Tissue
Carcinoma, Ductal, Breast
Salivary Gland Neoplasms
Nevi and Melanomas
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neuroendocrine Tumors