Study of Debio 0932 in Patients With Advanced Solid Tumours or Lymphoma
NCT ID: NCT01168752
Last Updated: 2014-02-03
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1
81 participants
INTERVENTIONAL
2010-04-30
2013-04-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Idelalisib+Obinutuzumab in Patients With Relapsed/Refractory Follicular Lymphoma
NCT03890289
DS-3201b in Participants With Lymphomas
NCT02732275
Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic of CC-95775 in Subjects With Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma
NCT04089527
Study to Evaluate an Oxaliplatin-based Chemotherapy in Patients With Resistant or Relapsing Non-Hodgkin Lymphoma.
NCT01019863
Study of OBINUTUZUMAB Combined to LENALIDOMIDE for the Treatment of Relapsed/Refractory Follicular and Aggressive B-cell Lymphoma
NCT01582776
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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.
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.
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.
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
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.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
* 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),
* 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.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Debiopharm International SA
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Hein van Ingen, M.D.
Role: STUDY_DIRECTOR
Debiopharm International SA
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Centre Georges-François Leclerc
Dijon, , France
Institut Claudius Regaud
Toulouse, , France
Institut Gustave Roussy
Villejuif, , France
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Croce CM. Oncogenes and cancer. N Engl J Med. 2008 Jan 31;358(5):502-11. doi: 10.1056/NEJMra072367. No abstract available.
Workman P, Burrows F, Neckers L, Rosen N. Drugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress. Ann N Y Acad Sci. 2007 Oct;1113:202-16. doi: 10.1196/annals.1391.012. Epub 2007 May 18.
Maloney A, Workman P. HSP90 as a new therapeutic target for cancer therapy: the story unfolds. Expert Opin Biol Ther. 2002 Jan;2(1):3-24. doi: 10.1517/14712598.2.1.3.
Kamal A, Boehm MF, Burrows FJ. Therapeutic and diagnostic implications of Hsp90 activation. Trends Mol Med. 2004 Jun;10(6):283-90. doi: 10.1016/j.molmed.2004.04.006.
Chiosis G, Vilenchik M, Kim J, Solit D. Hsp90: the vulnerable chaperone. Drug Discov Today. 2004 Oct 15;9(20):881-8. doi: 10.1016/S1359-6446(04)03245-3.
Mosser DD, Morimoto RI. Molecular chaperones and the stress of oncogenesis. Oncogene. 2004 Apr 12;23(16):2907-18. doi: 10.1038/sj.onc.1207529.
Obermann WM, Sondermann H, Russo AA, Pavletich NP, Hartl FU. In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis. J Cell Biol. 1998 Nov 16;143(4):901-10. doi: 10.1083/jcb.143.4.901.
Vilenchik M, Solit D, Basso A, Huezo H, Lucas B, He H, Rosen N, Spampinato C, Modrich P, Chiosis G. Targeting wide-range oncogenic transformation via PU24FCl, a specific inhibitor of tumor Hsp90. Chem Biol. 2004 Jun;11(6):787-97. doi: 10.1016/j.chembiol.2004.04.008.
Powers MV, Workman P. Targeting of multiple signalling pathways by heat shock protein 90 molecular chaperone inhibitors. Endocr Relat Cancer. 2006 Dec;13 Suppl 1:S125-35. doi: 10.1677/erc.1.01324.
Banerji U, Judson I, Workman P. The clinical applications of heat shock protein inhibitors in cancer - present and future. Curr Cancer Drug Targets. 2003 Oct;3(5):385-90. doi: 10.2174/1568009033481813.
Chiosis G, Lucas B, Huezo H, Solit D, Basso A, Rosen N. Development of purine-scaffold small molecule inhibitors of Hsp90. Curr Cancer Drug Targets. 2003 Oct;3(5):371-6. doi: 10.2174/1568009033481778.
Eccles SA, Massey A, Raynaud FI, Sharp SY, Box G, Valenti M, Patterson L, de Haven Brandon A, Gowan S, Boxall F, Aherne W, Rowlands M, Hayes A, Martins V, Urban F, Boxall K, Prodromou C, Pearl L, James K, Matthews TP, Cheung KM, Kalusa A, Jones K, McDonald E, Barril X, Brough PA, Cansfield JE, Dymock B, Drysdale MJ, Finch H, Howes R, Hubbard RE, Surgenor A, Webb P, Wood M, Wright L, Workman P. NVP-AUY922: a novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis. Cancer Res. 2008 Apr 15;68(8):2850-60. doi: 10.1158/0008-5472.CAN-07-5256.
Chandarlapaty S, Sawai A, Ye Q, Scott A, Silinski M, Huang K, Fadden P, Partdrige J, Hall S, Steed P, Norton L, Rosen N, Solit DB. SNX2112, a synthetic heat shock protein 90 inhibitor, has potent antitumor activity against HER kinase-dependent cancers. Clin Cancer Res. 2008 Jan 1;14(1):240-8. doi: 10.1158/1078-0432.CCR-07-1667.
Boll B, Eltaib F, Reiners KS, von Tresckow B, Tawadros S, Simhadri VR, Burrows FJ, Lundgren K, Hansen HP, Engert A, von Strandmann EP. Heat shock protein 90 inhibitor BIIB021 (CNF2024) depletes NF-kappaB and sensitizes Hodgkin's lymphoma cells for natural killer cell-mediated cytotoxicity. Clin Cancer Res. 2009 Aug 15;15(16):5108-16. doi: 10.1158/1078-0432.CCR-09-0213. Epub 2009 Aug 11.
Abramson JS, Chen W, Juszczynski P, Takahashi H, Neuberg D, Kutok JL, Takeyama K, Shipp MA. The heat shock protein 90 inhibitor IPI-504 induces apoptosis of AKT-dependent diffuse large B-cell lymphomas. Br J Haematol. 2009 Feb;144(3):358-66. doi: 10.1111/j.1365-2141.2008.07484.x. Epub 2008 Nov 13.
Hauschke D, Steinijans VW, Diletti E. A distribution-free procedure for the statistical analysis of bioequivalence studies. Int J Clin Pharmacol Ther Toxicol. 1990 Feb;28(2):72-8.
Isambert N, Delord JP, Soria JC, Hollebecque A, Gomez-Roca C, Purcea D, Rouits E, Belli R, Fumoleau P. Debio0932, a second-generation oral heat shock protein (HSP) inhibitor, in patients with advanced cancer-results of a first-in-man dose-escalation study with a fixed-dose extension phase. Ann Oncol. 2015 May;26(5):1005-1011. doi: 10.1093/annonc/mdv031. Epub 2015 Feb 2.
Related Links
Access external resources that provide additional context or updates about the study.
Study Sponsor
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2009-017720-11
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
Debio 0932-101
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.