Cancer, Lymphoma, Neoplasms, Solid Tumors
Conditions
Keywords
Cancer, solid tumour, lymphoma, dose-escalation, Hsp90 inhibitor
Brief summary
The purpose of this study is to determine the maximum tolerated dose of Debio 0932 when administered orally, every-other-day or daily during the first 30 days, in patients with solid tumours or lymphoma.
Detailed description
This is an open-label, non-randomised, dose-escalation phase I, pharmacokinetic and pharmacodynamic study in patients with advanced and/or refractory malignancies (solid tumours or lymphoma), to determine the maximum tolerated doses (MTD) of Debio 0932 administered orally every-other-day (schedule A) or every day (schedule B) and to assess its safety profile, pharmakokinetic, antitumor activity and pharmacodynamic biomarkers. Increments used in dose escalation will be determined according to the maximum grade of treatment-related adverse events observed during the first 30-day treatment period of each schedule in the previous in the preceding dose level Once reaching the recommended dose (RD) for each schedule, up to 40 additional patients will be enrolled and treated at the RD of the retained schedule, as part of an expansion phase.
Interventions
DRUGDebio 0932
Gelatin capsules of 2 dosage strengths (25 mg or 100 mg) The maximum dose will depend on the number of dose levels necessary to determine the MTD. In both schedules the study treatment will be continued, until one of the study treatment discontinuation criteria is met.
Sponsors
Debiopharm International SA
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of advanced solid tumours or lymphoma, except for primitive hepatocarcinoma for which radiological diagnosis only is permitted; * Advanced or metastatic disease refractory to standard curative or palliative therapy or contraindication or have refused standard therapy, * Measurable and/or evaluable disease, * Age ≥ 18 years, * ECOG performance ≤ 1 * Life expectancy ≥ 3 months, * If female, neither pregnant or lactating, * Negative pregnancy test for females at screening, preferably done within 1 week before Day 1 of treatment (not applicable to patients with bilateral oophorectomy and/or hysterectomy), * Agreeing to use appropriate medically approved contraception (physical barrier contraception is recommended) from study entry to 6 months after the last day of treatment for the patient, * Absolute neutrophil count ≥ 1,500/µL; platelets ≥ 100,000/µL; calculated creatinine clearance ≥ 60mL/min (calculated according to the formula of Cockroft and Gault); total bilirubin ≤ 1.5x ULN; AST/ALT ≤ 2.5x ULN. In patients with documented liver metastases, the AST/ALT may be ≤ 3.5x ULN; prothrombin time ≤1.5x ULN, kalemia, magnesemia and phosphatemia \> LLN (Lower Limit of Normal) * Able to render informed consent and to follow protocol requirements, * Able to swallow capsules, * Able to comply with scheduled plans, laboratory tests, and other study procedures.
Exclusion criteria
* Received investigational agents or systemic anti-cancer agents within 14 days of Day 1 of treatment, or 28 days for those agents with unknown elimination half-lives, or known elimination half-lives greater than 50 hours; or 6 weeks for Mitomycine C or for nitrosourea agents, * Unresolved toxicity from previous treatment or previous investigational agents, * Patients with history of prior radiation that potentially included the heart in the field (e.g. mantle), * Cardiac
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurence of DLTs for both schedules | 30 days | Occurrence of dose-limiting toxicities (DLTs) for both schedule A and schedule B |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of AEs, change in safety and efficacy parameters | Duration of study | Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), laboratory abnormalities, treatment discontinuations due to AEs for both schedules and expansion phase, change in 12-lead ECG (RR, PR, QRS, QT and QTcF intervals), rate of confirmed response, duration of response and disease control, pharmacodynamic biomarkers and drug pharmacokinetic parameters. |
Countries
France
Outcome results
None listed