DeuterOncology is recruiting patients for the clinical trial of Study to Determine the Safety and Pharmacokinetics of DO-2 in Patients With Advanced or Refractory Solid Tumours.
This study is a first-in-human, open-label, 2-part, Phase 1 dose escalation study of DO-2, administered orally to patients with advanced or refractory solid tumours, with MET aberrations, and no available, approved therapeutic alternative.
In Part 1, a Simon Design 3 accelerated titration design will be followed. One patient will be enrolled per cohort, until grade 2 toxicity is observed. Three sequential patients per cohort will be enrolled thereafter, with a minimum of 1 week between first dose administration in the first patient and the subsequent ones, in those latter cohorts.
The indicative duration of the clinical trial is from December 20, 2022 till June 2024.
Among primary outcome measures are the Determination of the Maximum Tolerated Dose (MTD) and The MTD in milligram is defined as the highest dose at which less than one third of the subjects in a dose level cohort experience DLT.
The study will take place at the Institut Roi Albert II - UC Louvain, Bruxelles, Belgium; UZA, Edegem, Belgium; Erasmus Medical Centre, Rotterdam, Netherlands.
Potential study participants must have:
- 18 years or older
histologically or cytologically confirmed advanced or refractory solid tumour and no longer eligible for approved, available standard therapies. Tumour types must have:
- 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
- proven amplification (≥ 10 copies) on archived tumour tissue. or
- Hereditary Renal Papillary Cancer
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- adequate bone marrow function, without the support of cytokines
- adequate liver function
- adequate renal function
- agree to follow the contraception requirements of the trial
- signed informed consent, indicating study patients understand the purpose of and procedures required for the study and are willing to participate in the study.
Whereas excluded from participation will be any patient who have any of the following:
- major surgery within 3 weeks before enrollment
- 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
- antibody based cancer therapy within 4 weeks before administration of the first dose of DO-2
patients with brain metastases are excluded unless all of the following criteria are met:
- CNS lesions are asymptomatic and previously treated
- No ongoing requirement for corticosteroids as therapy for CNS metastases
- Imaging demonstrates stability of disease > 28 days from last treatment for CNS metastases
- leptomeningeal involvement (leptomeningeal carcinomatosis)
- 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
- uncontrolled arterial hypertension despite appropriate therapy
- positive pregnancy test (urinary beta-hCG) at screening (applicable to women of child-bearing potential who are sexually active)
- mental status alteration or history of major psychiatric illness, which may potentially impair patient's compliance with study procedures
- signs and symptoms of active infection requiring systemic therapy
- other medical condition (e.g. pre-existing kidney dysfunction) that in the opinion of the investigator makes it undesirable for a patient to participate
The page dedicated to this clinical trial can be found here: https://ichgcp.net/clinical-trials-registry/NCT05752552