LBH589 Oral in Combination With Carboplatin and Paclitaxel in Advanced Solid Tumors
Recruitment status was: Active, not recruiting
|Advanced Solid Tumors||Drug: Panobinostat (LBH589), Carboplatin and Paclitaxel||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase IB Study of the Histone Deacetylase Inhibitor Panobinostat (LBH589) Given Orally in Combination With Carboplatin and Paclitaxel in Patients With Advanced Solid Tumors|
- Maximum Tolerated Dose (MTD) Recommended Dose (RD) [ Time Frame: 3 weeks after the first drug administration (1 Cycle) ]Number of Dose-Limiting Tocixities (DLTs)
- Hints of antitumor activity [ Time Frame: from first drug administration until tumor progression (every 6 weeks) ]objective tumor responses based on RECIST criteria
- Biomarkers of HDAC [ Time Frame: Cycle 1 on day 1, 4, 8, 15 and Cycle 2 on day 1, 8. ]acetylation of histones, H3, H4 and tubulin in PBMC
- Safety and tolerability [ Time Frame: 4 weeks after last drug administration ]AE types and frequency monitored by laboratory and instrumental assessments, and physical examination
|Study Start Date:||June 2008|
|Estimated Study Completion Date:||March 2012|
|Estimated Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
|Experimental: Panobinostat (LBH589), Carboplatin and Paclitaxel||
Drug: Panobinostat (LBH589), Carboplatin and Paclitaxel
The treatment will be repeated every three weeks until disease progression.
The combination of Carboplatin (C) and Paclitaxel (PTX) is considered standard treatment in patients with epithelial ovarian cancer and endometrial cancer, in USA and in those in whom anthracyclines are not recommended. In cervical cancer, where very often the renal function is impaired, C represents a convenient substitute of cisplatin in the combination with PTX; in NSCLC the C and PTX regimen is first choice therapy for outpatient treatment first or second line.
LBH is a histone deacetylase (HDAC) inhibitor available also for oral administration.
In combination with platinum agents LBH589 could improve efficacy on DNA by multiple non-exclusive mechanisms (by increasing drug access to chromosomal DNA, interfering with DNA repair, modulating the levels of pro antiapoptotic genes or proliferation/survival genes).
The inclusion of Paclitaxel in the combination of LBH589 and Carboplatin is supported by the results already available with the combination of the HDAC inhibitor Vorinostat (suberoylanilide hydroxamic acid) given orally with carboplatin (AUC 6 mg/ml.h) and paclitaxel (200 mg/m2) in a Phase I study in patients with solid tumors. The regimen proved to be feasible, well tolerated and was associated with promising antitumor activity in patients with NSCLC.
The mechanism of action, and the preliminary preclinical data, suggest that the combination of LBH589, Carboplatin and Paclitaxel could be feasible and worthy of clinical investigation.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01159418
|Basel, Switzerland, 4031|
|Istituto Oncologico della Svizzera Italiana|
|Bellinzona, Switzerland, 6500|
|Mèdecin Adjoint, ME - CePO, CHUV|
|Lausanne, Switzerland, 1011|