Cancer Clinical Trial
Official title:
Phase I Dose-escalation, Pharmacokinetic and Pharmacodynamic Study of Debio 0932, a Novel Hsp90-inhibitor, Administered Orally, in Patients With Advanced Solid Tumours or Lymphoma
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.
Status | Completed |
Enrollment | 81 |
Est. completion date | April 2013 |
Est. primary completion date | April 2013 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
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 exclusion criteria: - History of significant coronary artery disease or congestive heart failure that meets NYHA class III or IV, within 12 months (see Appendix D), - Significant cardiovascular dysfunction : pulmonary hypertension, right ventricular systolic dysfunction, aortic stenosis, mitral insufficiency > grade 2 and/or Left Ventricular Ejection fraction < 45% or < 55% if prior exposure to anthracyclines, based on MUGA or echocardiography, - Uncontrolled hypertension (Systolic > 150 or diastolic >100), - Permanent and uncontrolled cardiac rhythm disorders and clinical relevant abnormalities in 12-lead ECG/Holter, such as WPW (Wolff-Parkinson-White) syndrome, QRS > 120 msec, PR > 220 msec, heart rate < 50 bpm, Q wave, ST deviation, left bundle branch block, atrial fibrillation, flutter, tachysystoly. - Prolonged QTc interval > 450 msec in men and > 470 msec in women using Fridericia formula, - Congenital long QT syndrome, - Use of any medication associated with known QTc interval prolongation (a non-exhaustive list will be provided separately) - Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C, - Patients with uncontrolled brain metastases, - Gastrointestinal diseases or disorders that could affect drug absorption such as diarrhoea, major abdominal surgery, significant bowel obstruction and/or gastrointestinal diseases that could alter the assessment of safety, including any of the following: - Irritable bowel syndrome - Ulcerative colitis - Crohn disease - Haemorrhagic coloproctitis - Concurrent participation with any other anticancer therapy. |
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
France | Centre Georges-François Leclerc | Dijon | |
France | Institut Claudius Regaud | Toulouse | |
France | Institut Gustave Roussy | Villejuif |
Lead Sponsor | Collaborator |
---|---|
Debiopharm International SA |
France,
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* Note: There are 16 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Occurence of DLTs for both schedules | Occurrence of dose-limiting toxicities (DLTs) for both schedule A and schedule B | 30 days | Yes |
Secondary | Incidence of AEs, change in safety and efficacy parameters | 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. | Duration of study | Yes |
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