E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced solid tumors and Neurotrophic receptor tyrosine kinase (NTRK) gene fusion positive advanced solid tumors |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048683 |
E.1.2 | Term | Advanced cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Part A (Dose-escalation Phase): - Safety - Dose Limiting Toxicities (DLTs)
Part B (Expansion Phase): - Overall Response Rate (ORR) |
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E.5.1.1 | 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) |
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E.5.2 | 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) |
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E.5.2.1 | 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) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Dose-escalation, Expansion |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |