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

January 31, 2014 updated by: Debiopharm International SA

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

81

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Dijon, France, 21079
        • Centre Georges-Francois Leclerc
      • Toulouse, France, 31052
        • Institut Claudius Regaud
      • Villejuif, France, 94805
        • Institut Gustave Roussy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: schedule A

Debio 0932 will be administered orally to sequential escalating dose cohorts, as an every-other-day schedule.

Each dose level (DL) for each schedule will be determined according to the maximum grade of treatment-related AEs observed during the first 30 days treatment period (DLT period) in the previous DL.

Dose-escalation could be undertaken only after a minimum of 3 (or 6 in case of DLT) patients have been followed up and evaluated for at least 1 DLT period.
Drug: Debio 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.
Experimental: schedule B

Debio 0932 will be administered orally to sequential escalating dose cohorts, as a daily schedule.

Each dose level (DL) for each schedule will be determined according to the maximum grade of treatment-related AEs observed during the first 30 days treatment period (DLT period) in the previous DL.

Dose-escalation could be undertaken only after a minimum of 3 (or 6 in case of DLT) patients have been followed up and evaluated for at least 1 DLT period.
Drug: Debio 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurence of DLTs for both schedules
Time Frame: 30 days
Occurrence of dose-limiting toxicities (DLTs) for both schedule A and schedule B
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of AEs, change in safety and efficacy parameters
Time Frame: 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.
Duration of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Debiopharm International SA

Investigators

  • Study Director: Hein Van Ingen, M.D., Debiopharm International SA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2010

Primary Completion (Actual)

April 1, 2013

Study Completion (Actual)

April 1, 2013

Study Registration Dates

First Submitted

July 22, 2010

First Submitted That Met QC Criteria

July 22, 2010

First Posted (Estimate)

July 23, 2010

Study Record Updates

Last Update Posted (Estimate)

February 3, 2014

Last Update Submitted That Met QC Criteria

January 31, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Debio 0932-101
  • 2009-017720-11 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Neoplasms

Clinical Trials on Debio 0932

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in South Korea

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe