A Phase II Basket Study of the Oral TRK Inhibitor LOXO-101 in Subjects with NTRK Fusion-Positive Tumors

Phase 1

• Conditions: Solid Tumors; MedDRA version: 19.0Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-003582-28-ES
• Lead Sponsor: oxo Oncology Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-06-07
• Last Update Posted: 13 June 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 151

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:
a. Have received prior treatment including radiation and/or chemotherapy, with radiation completed > 12 weeks prior to C1D1 of therapy, as recommended or appropriate for that CNS tumor type.
b. 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.
c. 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. At least 18 years of age.
5. Eastern Cooperative Oncology Group (ECOG) score of ? 2.
6. 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.
7. Adequate organ function as defined by the following criteria:
a. 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.
b. Total bilirubin < 2.5 × 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.
c. Serum creatinine < 2.0 × ULN OR an estimated glomerular filtration rate ? 30 mL/minute using the Cockroft-Gault formula:
(140 ? age) x body weight (kg) × 0.85 (if female)
serum creatinine (mg/dL) × 72
8. Ability to swallow capsules, comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation.
9. Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 3 months following study completion.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 76

Exclusion Criteria

1. Investigational agent or anticancer therapy within 2 weeks prior to planned start of LOXO-101 or 5 half-lives, whichever is shorter, and with recovery of clinically significant toxicities from that therapy.
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.
3. Uncontrolled concurrent malignancy that would limit assessment of efficacy of LOXO-101.
4. Active uncontrolled systemic bacterial, viral, or fungal infection, unstable cardiovascular disease or other systemic disease that would limit compliance with study procedures.
5. Malabsorption syndrome or other condition affecting oral absorption.
6. Inability to discontinue treatment with a strong CYP3A4 inhibitor or inducer prior to start of treatment initiation.
7. Pregnancy or lactation.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified