A Phase 1 Study to Determine the Safety, and Pharmacokinetics of the Selective MET kinase Inhibitor, DO-2 in Patients With Advanced or Refractory Solid Tumours
- Conditions
- All Advanced or Refractory Solid TumoursAdvanced or Refractory Solid Tumours
- Registration Number
- NL-OMON51802
- Lead Sponsor
- DeuterOncology NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 15
1. 18 years or older
2. histologically or cytologically confirmed advanced or refractory solid
tumour and no longer eligible for approved, available standard therapies.
Tumour types must have:
a. proven MET activating mutations, determined by previous next generation
sequencing (NGS), whole exome sequencing (WES), whole transcriptome sequencing
(WTS) or other genomic analysis methods,
or
b. proven amplification (>= 10 copies) on archived tumour tissue.
or
c. Hereditary Renal Papillary Cancer
3. Eastern Cooperative Oncology Group (ECOG) performance status of <= 2
4. adequate bone marrow function, without the support of cytokines: white blood
cell count (WBC) >3,000/mm3, absolute neutrophil count (ANC) >1,500/mm3,
platelet count >100,000/mm3, hemoglobin >10 g/dL
5. adequate liver function: total bilirubin level <= 1.5 x institutional upper
limit of normal (ULN), alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) <= 2.5 x institutional ULN in the absence of liver
metastasis, or <= 5.0 x institutional ULN in the presence of liver metastasis
6. adequate renal function with serum creatinine <= 1.5 x institutional ULN and
GFR of 60mL/min or higher by Cockroft-Gault formula. See Attachment 1.
7. agree to follow the contraception requirements of the trial as described in
section 4.4.
8. signed informed consent, indicating study patients understand the purpose of
and procedures required for the study and are willing to participate in the
study.
1. major surgery within 3 weeks before enrollment
2. chemotherapy (in the case of nitrosoureas and mitomycin C within 6 weeks),
radiotherapy, immunotherapy, or any other study drug within 3 weeks before
study drug administration
3. antibody based cancer therapy within 4 weeks before administration of the
first dose of DO-2
4. patients with brain metastases are excluded unless all of the following
criteria are met:
a. CNS lesions are asymptomatic and previously treated
b. No ongoing requirement for corticosteroids as therapy for CNS metastases
c. Imaging demonstrates stability of disease >= 28 days from last treatment for
CNS metastases
5. leptomeningeal involvement (leptomeningeal carcinomatosis)
6. history of uncontrolled heart disease including unstable angina, congestive
heart failure, myocardial infarction within preceding 12 months, clinically
significant rhythm or conduction abnormality, congenital long QT syndrome,
obligate use of a cardiac pacemaker, QTc at screening greater than 450
milliseconds in males and greater than 470 milliseconds in females.
7. uncontrolled arterial hypertension: systolic blood pressure of 160 mmHg or
greater or diastolic blood pressure of 100 mmHg or greater or both, despite
appropriate therapy.
8. positive pregnancy test (urinary beta hCG) at screening (applicable to women
of child-bearing potential who are sexually active)
9. mental status alteration or history of major psychiatric illness, which may
potentially impair patient*s compliance with study procedures
10. signs and symptoms of active infection requiring systemic therapy
11. other medical condition (e.g. pre-existing kidney dysfunction) that in the
opinion of the investigator makes it undesirable for a patient to participate
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• Determine the recommended dose for further clinical studies.<br /><br>• Assess the preliminary antitumor activity in 3 defined cohorts.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Not applicable</p><br>