Know Cancer

forgot password

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

Phase 1
18 Years
Open (Enrolling)
Cancer, Neoplasms, Solid Tumors, Lymphoma

Thank you

Trial Information

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

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.

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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Occurence of DLTs for both schedules

Outcome Description:

Occurrence of dose-limiting toxicities (DLTs) for both schedule A and schedule B

Outcome Time Frame:

30 days

Safety Issue:


Principal Investigator

Hein van Ingen, M.D.

Investigator Role:

Study Director

Investigator Affiliation:

Debiopharm S.A.


France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Study ID:

Debio 0932-101



Start Date:

April 2010

Completion Date:

March 2013

Related Keywords:

  • Cancer
  • Neoplasms
  • Solid Tumors
  • Lymphoma
  • Cancer
  • solid tumour
  • lymphoma
  • dose-escalation
  • Hsp90 inhibitor
  • Neoplasms
  • Lymphoma