Study of ONO-7579 in Patients With Advanced Solid Tumors/ NTRK Gene Fusion Positive Advanced Solid Tumors

NCT03182257 | Terminated Phase 1 FDA Drug

• 1 other identifier: ONO-7579-01
• Study Type: interventional
• Target: 1
• Locations: 2 countries
• Sites: 5

Brief Summary

This study will determine the safety and maximum tolerated dose of ONO-7579 in patients with advanced solid tumors, and evaluate efficacy of ONO-7579 in patients with advanced solid tumors harboring NTRK gene fusions.

Conditions

Solid Tumor

Keywords

TRK; TRKA; TRKB; TRKC; NTRK1; NTRK2; NTRK3; NTRK fusion positive; NTRK1 fusion; NTRK2 fusion; NTRK3 fusion; NTRK1 gene rearrangement; NTRK2 gene rearrangement; NTRK3 gene fusion; ETV6-NTRK3; fusion; tumors; solid tumors; CNS tumors; central nervous system tumors; TRK fusion; ETV6; ETV6 fusion; solid CNS tumor; advanced CNS tumor; primary CNS tumor

Outcome Measures

Primary Outcomes (5)

• Part A: Incidence, nature and severity of Adverse Events

  To investigate the safety and tolerability of ONO-7579 to determine MTD/RCD

  up to 28 days

• Part A: Clinically significant changes in physical examinations

  To investigate the safety and tolerability of ONO-7579 to determine MTD/RCD

  up to 28 days

• Part A: Clinically significant changes in neurological examinations

  To investigate the safety and tolerability of ONO-7579 to determine MTD/RCD

  up to 28 days

• Part A: Clinically significant changes in vital signs and electrocardiogram - including the evaluation of the QT interval

  To investigate the safety and tolerability of ONO-7579 to determine MTD/RCD

  up to 28 days

• Part B: Overall Response Rate (ORR)

  Assessed by Independent Central Review using RECIST 1.1 or RANO criteria

  up to 24 months

Secondary Outcomes (16)

• Part A and B Pharmacokinetics (Cmax)

  Day 1, 2, 7, 14 and 28

• Part A and B Pharmacokinetics (Tmax)

  Day 1, 2, 7, 14 and 28

• Part A and B Pharmacokinetics (AUC)

  Day 1, 2, 7, 14 and 28

• Part A and B Pharmacokinetics (T1/2)

  Day 1, 2, 7, 14 and 28

• Part A and B Pharmacokinetics (Ctrough)

  Day 1, 2, 7, 14 and 28

Study Arms (2)

ONO-7579 Part A

EXPERIMENTAL

Single Ascending doses of ONO-7579

Drug: ONO-7579

ONO-7579 Part B

EXPERIMENTAL

Expansion phase of ONO-7579

Drug: ONO-7579

Interventions

ONO-7579 DRUG

ONO-7579 Tablets

ONO-7579 Part A; ONO-7579 Part B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged at least 18 years or older, at the time of signing the informed consent form.
• The patient (or their legal representative) has provided written informed consent, which signifies an agreement to enter the study and comply with the restrictions and requirements listed in the informed consent form.
• ECOG performance status ≤ 2
• Life expectancy of at least 3 months
• Patients must have measurable disease, according to RECIST 1.1 (defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm (≥2 cm) with conventional techniques or as ≥10 mm (≥1 cm) with spiral CT scan), or RANO criteria for Glioma.
• Adequate hematologic, hepatic and renal function as defined by the following criteria:
• Absolute Neutrophil count ≥ 1.5x109
• Platelet count ≥ 75,000 / mm3
• Hemoglobin level ≥ 9.0 g/dL
• Total Bilirubin level ≤ 1.5 X ULN
• AST and ALT ≤ 3 X ULN
• Creatinine clearance\* ≥50 mL/min \*estimated CLcr by the Cockcroft-Gault equation
• 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. Acceptable forms of effective contraception include;
• Established use of oral, injected or implanted hormonal methods of contraception.

You may not qualify if:

• Radiotherapy within two weeks prior to study entry
• Major surgery (excluding placement of vascular access) within 4 weeks before the first dose of study treatment
• 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
• 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.
• Concurrent treatment with another investigational agent or participated in another investigational trial within 30 days of study entry
• Diagnosed or treated for a malignancy other than the tumor under investigation in the study within 5 years, or who were previously diagnosed with a malignancy other than that required for the study and have any radiographic or biochemical marker evidence of that malignancy. Patients with completely resected basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy are not excluded.
• 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
• 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
• Serious concurrent medical conditions, including serious active infection, in the opinion of the investigator
• Female patients who are pregnant or breast feeding

Sponsors & Collaborators

• Ono Pharmaceutical Co. Ltd: lead

Study Sites (5)

Montefiore Medical Center

Lake Success, New York, 11041, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

Greenville Hospital System University Medical Center

Greenville, South Carolina, 29605, United States

Location

Mary Crowley Cancer Research Center

Dallas, Texas, 75230, United States

Location

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, G12 0YN, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms; Central Nervous System Neoplasms

Interventions

ONO-7579

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Study Officials

• Drug Development Division

  Ono Pharmaceutical Co. Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2017
• First Posted: June 9, 2017
• Study Start: July 12, 2017
• Primary Completion: January 30, 2018
• Study Completion: January 30, 2018
• Last Updated: September 13, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); US (4)