Study of Debio 0932 in Patients With Advanced Solid Tumours or Lymphoma

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.