Advanced solid tumors and Neurotrophic receptor tyrosine kinase (NTRK) gene fusion positive advanced solid tumors MedDRA version: 19.1 Level: LLT Classification code 10048683 Term: Advanced cancer System Organ Class: 100000004864
Conditions
Interventions
Product Code: ONO-7579 1mg
Pharmaceutical Form: Tablet
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: ONO-7579TS
Sponsors
Ono Pharmaceutical Co., Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Common criteria for Part A and B: 1. Male or female aged at least 18 years or older, at the time of signing the informed consent form. 2. ECOG performance status = 2. 3. Life expectancy of at least 3 months. 4. Patients must have a measurable disease, according to RECIST 1.1 or RANO criteria for Glioma. 5. Patients must have received at least one prior line of therapy appropriate for their tumor type and stage of disease. For glioma, patient must have received at least one prior treatment with radiotherapy and Temozolomide. Prior treatment of any Trk inhibitor(s) is not an exclusion. 6. Adequate hematologic, hepatic and renal function. 7. Women of childbearing potential must have a negative serum pregnancy test documented within 14 days prior to enrollment, and must agree to use two adequate methods of contraception from Day 1 of the study until 3 months after the end of treatment. 8. Women of non-childbearing potential, defined as females with a documented history of a clinically recognized procedure (e.g. hysterectomy, tubal ligation, bilateral salpingo-/oophorectomy); or postmenopausal. Additional Criterion for Part A only 1. Patients with histologically/cytologically confirmed advanced solid tumors, and documented tumor progression for whom no further standard anticancer treatment is available. Additional Criteria for Part B only 1. Patients with histologically/cytologically confirmed advanced solid tumors and documented tumor progression for whom no further standard anti-cancer treatment exists or where, in the opinion of the investigator, the existing standard anti-cancer treatment options available are not expected to provide a reasonable benefit to the patient. 2. Patient requires treatment with systemic anti-cancer therapy, in the opinion of the investigator. 3. Patients must have NTRK1, NTRK2 or NTRK3 gene fusion confirmed locally prior to first dose. 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 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: Common Criteria of Part A and B: 1. Radiotherapy within two weeks prior to study entry. 2. Major surgery (excluding placement of vascular access) within 4 weeks before the first dose of study treatment. 3. Spinal cord compression or brain metastases unless treated and radiologically stable for >6 weeks post treatment and not requiring steroids for at least 4 weeks prior to start of study treatment. 4. As judged by the Investigator, any evidence of severe or uncontrolled psychiatric disease or systemic diseases, including history of suicide attempt or current suicidal ideation or behavior, active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required. 5. Clinically significant cardiovascular disease, including: - History of myocardial infarction, acute coronary syndromes (including unstable angina), or coronary angioplasty/stenting/bypass grafting within the past 6 months. - History of Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system - Severe cardiac arrhythmia requiring medication or other severe conduction abnormalities (e.g. clinically significant QT prolongation or Torsade de pointes) - Uncontrolled hypertension - Clinically significant valvular disease, cardiomegaly, ventricular hypertrophy, or cardiomyopathy 6. QT prolongation defined as a QTcF interval >470 msec or other significant ECG abnormalities including 2nd degree (type II) or 3rd degree AV block or bradycardia (ventricular rate <50 beats/min) on 12-lead ECG at screening. 7. Serious concurrent medical conditions, including serious active infection, in the opinion of the investigator. 10. Female patients who are pregnant or breast-feeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A (Dose-escalation Phase): To investigate the safety and tolerability of ONO-7579 and to determine the maximum tolerated dose (MTD)/recommended clinical dose (RCD) of ONO-7579 for further evaluation in Part B Part B (Expansion Phase): To evaluate the efficacy of ONO-7579 ; Secondary Objective: Part A (Dose-escalation Phase): - To evaluate the preliminary anti-tumor efficacy of ONO-7579 in patients with advanced solid tumors. - To evaluate the pharmacokinetics (PK) of ONO-7579 in plasma and urine - To evaluate food effect on the PK of ONO-7579 Part B (Expansion Phase): - To evaluate clinical benefit - To evaluate the safety of ONO-7579 - To evaluate the PK of ONO-7579 in plasma ; Primary end point(s): Part A (Dose-escalation Phase): - Safety - Dose Limiting Toxicities (DLTs) Part B (Expansion Phase): - Overall Response Rate (ORR) ; Timepoint(s) of evaluation of this end point: Part A (Dose-escalation Phase): - End of Part A (expected June 2018) Part B (Expansion Phase): - End of Part B (expected September 2020) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Part A (Dose-escalation Phase): - End of Part A (expected June 2018) Part B (Expansion Phase): - End of Part B (expected September 2020) ; Secondary end point(s): Part A (Dose-escalation Phase): - Overall Response Rate (ORR) - Duration of Response (DoR) - Progression Free Survival (assessed at 6 and 12 months) - The pharmacokinetics (PK) of and food effect on ONO-7579 (Cmax, Tmax, AUC, T1/2, Ctrough, Ae) Part B (Expansion Phase): - Progression Free Survival - Duration of Response (DoR) - Overall Survival - Time to Progression - Time to Response - Safety (assessed by incidence of AEs, physical examination, neurological examinations, clinical laboratory tests, vital signs and 12-lead ECGs [including evaluation of QT]) - The PK of ONO-7579 (Cmax, Tmax, AUC, T1/2, Ctrough) | — |
Countries
United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Ono Pharma UK Ltd
Outcome results
None listed