A phase 1/2 study of the investigational treatment LOXO-195 in adults and minors that have a previously treated cancer with a change in a gene called NTRK.
- Conditions
- TRK fusion cancers previously treated with a TRK inhibitorMedDRA version: 21.0Level: LLTClassification code 10049516Term: Malignant tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10007958Term: Central nervous system neoplasmSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-004246-20-IT
- Lead Sponsor
- Bayer Consumer Care AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 103
1.Advanced solid tumor for which, in the opinion of the Investigator, no other standard therapy offers greater benefit.
2.A solid tumor diagnosis in the setting of:
a.a documented NTRK fusion and a clinical history of relapse following a response to a prior TRK inhibitor
b.a documented NTRK fusion unresponsive to a prior TRK inhibitor
c.a documented NTRK fusion and a clinical history of intolerance to a prior TRK inhibitor
3.NTRK (NTRK1, NTRK2, and NTRK3) gene fusions will be identified in a CLIA certified (or equivalent) laboratory.
4.Performance Status: Eastern Cooperative Oncology Group (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%.
5.Evaluable and/or measurable disease by RECIST v1.1 or RANO.
6.Life expectancy 4 weeks.
7.At least 1 month of age.
8.Tissue submission. Samples from 2 time points are required if available
9.Adequate hematologic function, for patients without known bone marrow involvement, defined as:
a.Hemoglobin (Hb) = 8.0 g/dL
b.Absolute neutrophil count (ANC) = 1.0 × 109 /L
c.Platelets (Plt) = 100 × 109 /L without need for regular transfusion support
Patients with known bone marrow involvement will not be evaluable for hematologic DLT and can enroll with:
a.Hb = 8.0 g/dL (transfusions allowed)
b.ANC = 0.75 × 109 /L
c.Plt = 50 × 109 /L (transfusions allowed)
10.Adequate hepatic function defined as:
a.AST and ALT =2.5 × upper limit of normal (ULN) or =5 × ULN if in the setting of liver metastases
b.Total bilirubin =1.5 × ULN or =3 × ULN if in the setting of liver metastases or Gilbert's disease; patients with higher total bilirubin levels due to Gilbert's disease or hepatic metastases may be enrolled with Sponsor approval
11.For patients age 18 years and older: Adequate renal function defined as serum creatinine =2.0 mg/dL or estimated glomerular filtration = 30 mL/min using Cockcroft-Gault formula.
For patients up to age 18 years: Estimated glomerular filtration rate = 30 mL/minute/1.73 m2 based on local institutional practice for determination OR a serum creatinine based on age/gender
12.At least 5 half-lives since most recent kinase inhibitor dose OR at least 7 days since last systemic anticancer therapy (whichever is shorter) and recovered to baseline from all toxicity of last cytotoxic chemotherapy dose. Alopecia and other non-acute toxicities are acceptable.
13.Patients with stable CNS primary tumor, brain metastases, or treated spinal cord compression are eligible if neurological symptoms have been stable for 7 days prior to the first dose of LOXO-195 and there has been no change in steroid dose, if taking steroids to manage CNS symptoms, for 7 days prior to the first dose of LOXO-195. The patient can be receiving any dose of steroids is as long as dosing meets specifications noted above.
14.Negative serum pregnancy test prior to C1D1 study drug if a woman of child-bearing potential. Surgically sterilized women are exempt.
15.Agreement to adequate contraception in male and female patients with reproductive potential for the duration of treatment and for 6 months following study completion.
a.Willingness to use double effective birth control methods, defined as one used by the patient and another by his/her partner.
b.Oral contraception should always be combined with an additional contraceptive method
1.If received recent therapy, evidence of unstable organ dysfunction due to treatment.
2.Concurrent treatment with a strong CYP3A4 inhibitor or inducer or drugs associated with QT prolongation. The Investigator should review concomitant medications with their site pharmacist as the list can change frequently.
3.Clinically significant active cardiovascular disease or history of myocardial infarction within 3 months prior to planned start of LOXO-195, cardiomyopathy; current or known history within the past 6 months of prolonged QTc interval >480 milliseconds. If there is a known explanation for a limited period of a prolonged QT interval (i.e., a medication known to cause prolonged QT interval was administered and has since been discontinued with clearly documented normal QT interval thereafter), that subject may be enrolled.
4.Major surgery within 7 days of enrollment. Catheter placement, endoscopic procedures, and dental surgery are not considered major surgery.
5.Uncontrolled systemic bacterial, fungal or viral infection. Infections treated with a stable dose of antimicrobial therapy for at least 7 days are allowed.
6.Pregnancy or lactation.
7.Known hypersensitivity to any of the components of the investigational agent, LOXO-195 or Ora-Sweet® SF and OraPlus®, for patients who will take the LOXO-195 suspension
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method