NCT01159418

LBH589 Oral in Combination With Carboplatin and Paclitaxel in Advanced Solid Tumors

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

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: Southern Europe New Drug Organization · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine the Maximum Tolerated Dose (MTD) of Panobinostat (LBH589) when administered in combination with Carboplatin and Paclitaxel in patients with advanced solid malignancies and to identify the Recommended Dose (RD) for a subsequent Phase II study.

Detailed description

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.

Conditions

• Advanced Solid Tumors

Interventions

Type	Name	Description
DRUG	Panobinostat (LBH589), Carboplatin and Paclitaxel	1. Panobinostat (LBH589) p.o. on days 1,4,8 and 11 of each cycle (20mg-45mg).Carboplatin i.v.on day 1 at a total dose corresponding to a AUC of 5 µg/ml.h. Paclitaxel as 3 hour infusion on day 1 (135 mg/m2). 2. Panobinostat (LBH589) p.o. on days 1, 4, 15 and 18 of each cycle (20mg-30mg).Carboplatin i.v. on day 8 at a total dose corresponding to a AUC of 5 µg/ml.h.Paclitaxel as a 3 hour infusion on day 8 (135mg/m2-175mg/m2). 3. Once the MTD is achieved:Panobinostat (LBH589) p.o. on days 1 and 4 of each cycle(20mg-30 mg). Carboplatin i.v. on day 8 at a total dose corresponding to a AUC of 5 µg/ml.h.Paclitaxel as a 3 hour infusion on day 8 (135mg/m2-175 mg/m2). The treatment will be repeated every three weeks until disease progression.

Timeline

• Start date: 2008-06-01
• Primary completion: 2011-12-01
• Completion: 2012-03-01
• First posted: 2010-07-09
• Last updated: 2011-09-13

Locations

3 sites across 1 country: Switzerland