Clinical Trials /

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

NCT03182257

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of ONO-7579 in Patients With Advanced Solid Tumors/ NTRK Gene Fusion Positive Advanced Solid Tumors
  • Official Title: An Open-label, Multi-center, Dose-escalation and Expansion Study to Evaluate the Safety and Efficacy of ONO-7579 in Patients With Advanced Solid Tumors/ NTRK Gene Fusion Positive Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: ONO-7579-01
  • NCT ID: NCT03182257

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
ONO-7579ONO-7579 Part A

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
ONO-7579 Part AExperimentalSingle Ascending doses of ONO-7579
  • ONO-7579
ONO-7579 Part BExperimentalExpansion phase of ONO-7579
  • ONO-7579

Eligibility Criteria

        Inclusion Criteria (Parts A and B):

          1. Male or female aged at least 18 years or older, at the time of signing the informed
             consent form.

          2. 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.

          3. ECOG performance status ≤ 2

          4. Life expectancy of at least 3 months

          5. 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.

          6. 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.

          7. 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

          8. Women of:

               1. 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.

                    -  Placement of an intrauterine device or intrauterine system.

                    -  Barrier methods of contraception: condom or occlusive cap (diaphragm or
                       cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.

                    -  Male sterilization (with the appropriate post-vasectomy documentation of
                       the absence of sperm in the ejaculate).

               2. Non-childbearing potential, defined as pre-menopausal females with a documented
                  tubal ligation or hysterectomy; or postmenopausal defined as 12 months of
                  spontaneous amenorrhea with follicle-stimulating hormone (FSH) >40 MlU/mL).
                  Females on hormone replacement therapy (HRT) will be required to use one of the
                  contraception methods in Inclusion criteria 8a or must discontinue HRT to allow
                  confirmation of post-menopausal status prior to being enrolled in the study.
                  Following confirmation of their post-menopausal status, they can resume HRT
                  during the study and will not be required to use contraception.

          9. A male patient is eligible to participate if he is not trying to father a child and
             is willing to use one of the relevant contraception methods as in inclusion criterion
             8a from Day 1 of the study until 3 months after the end of treatment.

         10. Able to swallow tablets

         11. Patients must be recovered to Grade 1 from the effects (excluding alopecia) of any
             prior therapy for their malignancies.

             Additional Criterion for Part A only

         12. Patients with histologically/cytologically confirmed advanced solid tumors, and
             documented tumor progression for whom no further standard anticancer treatment is
             available.

         13. Patients must be able to comply with the protocol requirements regarding fasting, as
             determined by the investigator (excluding patients in food assessment cohort(s)).

             Additional Criteria for Part B only

         14. Patients with histologically/cytologically confirmed advanced solid tumors and
             documented tumor progression for whom no further standard anticancer treatment exists
             or where, in the opinion of the investigator, the existing standard anticancer
             treatment options available are not expected to provide a reasonable benefit to the
             patient.

         15. Patients must have NTRK1, NTRK2 or NTRK3 gene fusion confirmed locally prior to first
             dose.

        Exclusion Criteria:

          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. Concurrent treatment with another investigational agent or participated in another
             investigational trial within 30 days of study entry

          6. 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.

          7. 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

          8. 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

          9. Serious concurrent medical conditions, including serious active infection, in the
             opinion of the investigator

         10. Female patients who are pregnant or breast feeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part A: Incidence, nature and severity of Adverse Events
Time Frame:up to 28 days
Safety Issue:
Description:To investigate the safety and tolerability of ONO-7579 to determine MTD/RCD

Secondary Outcome Measures

Measure:Part A and B Pharmacokinetics (Cmax)
Time Frame:Day 1, 2, 7, 14 and 28
Safety Issue:
Description:Assessment of the maximum plasma concentration of ONO-7579
Measure:Part A and B Pharmacokinetics (Tmax)
Time Frame:Day 1, 2, 7, 14 and 28
Safety Issue:
Description:Assessment of the time to reach maximum observed plasma concentration of ONO-7579
Measure:Part A and B Pharmacokinetics (AUC)
Time Frame:Day 1, 2, 7, 14 and 28
Safety Issue:
Description:Assessment of the plasma area under the curve from time zero to 24 hours after dosing
Measure:Part A and B Pharmacokinetics (T1/2)
Time Frame:Day 1, 2, 7, 14 and 28
Safety Issue:
Description:Assessment of the plasma decay half life of ONO-7579
Measure:Part A and B Pharmacokinetics (Ctrough)
Time Frame:Day 1, 2, 7, 14 and 28
Safety Issue:
Description:Assessment of the trough concentration of ONO-7579 in plasma
Measure:Part A Overall Response Rate (ORR)
Time Frame:up to 28 days
Safety Issue:
Description:Assessed by investigator using RECIST 1.1 or RANO criteria
Measure:Part A Duration of Response (DoR)
Time Frame:up to 28 days
Safety Issue:
Description:Assessed by investigator using RECIST 1.1 or RANO criteria
Measure:Part A Progression Free Survival (PFS)
Time Frame:up to 28 days
Safety Issue:
Description:Assessed by investigator using RECIST 1.1 or RANO criteria
Measure:Part B Progression Free Survival (PFS)
Time Frame:up to 24 months
Safety Issue:
Description:Assessed by Independent Central Review using RECIST 1.1 or RANO criteria
Measure:Part B Overall Survival (OS)
Time Frame:up to 24 months
Safety Issue:
Description:Assessed by Independent Central Review using RECIST 1.1 or RANO criteria
Measure:Part B Time to Response (TTR)
Time Frame:up to 24 months
Safety Issue:
Description:Assessed by Independent Central Review using RECIST 1.1 or RANO criteria
Measure:Part B Time to Progression (TTP)
Time Frame:up to 24 months
Safety Issue:
Description:Assessed by Independent Central Review using RECIST 1.1 or RANO criteria
Measure:Part B Incidence, nature and severity of Adverse Events
Time Frame:up to 24 months
Safety Issue:
Description:To determine the safety and tolerability of ONO-7579
Measure:Part B: Clinically significant changes in physical examinations
Time Frame:up to 24 months
Safety Issue:
Description:To determine the safety and tolerability of ONO-7579
Measure:Part B: Clinically significant changes in neurological examinations
Time Frame:up to 24 months
Safety Issue:
Description:To determine the safety and tolerability of ONO-7579
Measure:Part B: Clinically significant changes in vital signs and electrocardiogram - including the evaluation of the QT interval
Time Frame:up to 24 months
Safety Issue:
Description:To determine the safety and tolerability of ONO-7579

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Ono Pharmaceutical Co. Ltd

Trial 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

Last Updated

June 8, 2017