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

a study on Lung Cancer Thyroid Cancer Sarcoma Colorectal Cancer Salivary Gland Neoplasms Biliary Tract Cancer Brain Tumor Carcinoma, Ductal, Breast Melanoma Skin Cancer/Melanoma Solid Tumor Astrocytoma Glioblastoma Glioma Cholangiocarcinoma Head and Neck Squamous Cell Carcinoma Squamous Cell Carcinoma Pancreatic Cancer Ovarian Cancer Renal Cell Carcinoma Carcinoma Carcinoma, Bronchogenic Bronchial Neoplasms Lung Tumor Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms, Nerve Tissue

Summary

for people ages 12 years and up (full criteria)
at UCLA
study started
estimated completion

Description

Summary

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

Official Title

A Phase II Basket Study of the Oral TRK Inhibitor LOXO-101 (Larotrectinib) in Subjects With NTRK Fusion-Positive Tumors

Details

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.

Keywords

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 NTRK Fusion Positive LOXO-101 Loxo TRK TRK Fusion NTRK1 NTRK2 NTRK3 TRKA TRKB TRKC ETV6 NTRK larotrectinib fusion tumors CNS 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 Neoplasms Carcinoma, Squamous Cell Head and Neck Neoplasms Brain Neoplasms Carcinoma, Ductal Larotrectinib LOXO-101 Thyroid Colorectal Salivary Biliary All Other Solid Tumors

Eligibility

For people ages 12 years and up

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:
  4. 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.
  5. 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
  6. Serum creatinine < 2.0 x ULN OR an estimated glomerular filtration rate ≥ 30 mL/minute using the Cockcroft-Gault formula
  7. 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%
  8. 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.

Locations

  • University of California - Los Angeles accepting new patients
    Los Angeles California 90095 United States
  • Stanford University accepting new patients
    Stanford California 94305 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Bayer
ID
NCT02576431
Phase
Phase 2
Study Type
Interventional
Last Updated