A Multicenter, Open-Label, Dose-Escalating Phase I Trial of the DNA-PK Inhibitor MSC2490484A in Subjects With Advanced Solid Tumors or Chronic Lymphocytic Leukemia
- Conditions
- solid tumors and Chronic Lymphocytic Leukemia10024324
- Registration Number
- NL-OMON41861
- Lead Sponsor
- Merck
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
*Advanced solid tumors likely to have alterations in DNA repair mechanisms, such as the BRCA and ATM pathways), or CLL, with no other standard surgical, radiation, or systemic anticancer therapies available;*Tumor accessible for biopsies and agree to pretreatment tumor biopsy;*Measurable or evaluable disease in accordance with RECIST v 1.1 for solid tumors or Cheson*s criteria for CLL;*Male or female subjects at least 18 years of age who sign written informed consent.
1. Eastern Cooperative Oncology Group performance status > 1;2. Received:
a. Chemotherapy, immunotherapy, hormonal therapy with the exception
of luteinizing hormone releasing hormone (LHRH) analogs, biologic
therapy, or any other anticancer therapy within 28 days prior to the first
dose of IMP administration (6 weeks for nitrosoureas or mitomycin C)
b. Any investigational agent within 28 days prior to the first dose of IMP
administration
c. Extensive prior radiotherapy on more than 30% of bone marrow
reserves or prior bone marrow/stem cell transplantation within 5 years
before study start. The extent of previous radiotherapy to the bone
marrow will be determined by the investigator
3. Subjects currently receiving (or unable to stop using prior to receiving
the first dose of trial drug) medications or herbal supplements known to
be potent inhibitors of CYP3A or CYP2C19 (must stop at least 1 week
prior), potent inducers of CYP3A or CYP2C19 (must stop at least 3 weeks
prior), or drugs mainly metabolized by CYP3A with a narrow therapeutic
index (must stop at least one day prior)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Number of Dose Limiting Toxicities (DLTs) occurring in Cycle 1</p><br>
- Secondary Outcome Measures
Name Time Method <p>1) Pharmacokinetics profile in plasma (Cmax, tmax, Cmin, Cavg, fluctuation<br /><br>indices (peak-to-trough fluctuation and swing), AUC0-24, AUC0-12,<br /><br>AUC0-t, AUC0-*, AUC*, t1/2, *z, CL/f, Vz/f, Vss/f, Racc(AUC), and Racc(Cmax)<br /><br>2)Best overall response rate<br /><br>3) Clinical benefit rate defined as the proportion of subjects with Complete<br /><br>Response, Partial Response, or stable disease at Week 12<br /><br>4) Progression-free survival time (PFS)</p><br>