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

NCT01159418 | Unknown Phase 1

• 1 other identifier: SKSD00702
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Advanced Solid Tumors

Keywords

solid tumors; Panobinostat; histone deacetylase inhibitors

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) Recommended Dose (RD)

  Number of Dose-Limiting Tocixities (DLTs)

  3 weeks after the first drug administration (1 Cycle)

Secondary Outcomes (3)

• Hints of antitumor activity

  from first drug administration until tumor progression (every 6 weeks)

• Biomarkers of HDAC

  Cycle 1 on day 1, 4, 8, 15 and Cycle 2 on day 1, 8.

• Safety and tolerability

  4 weeks after last drug administration

Study Arms (1)

Panobinostat (LBH589), Carboplatin and Paclitaxel

EXPERIMENTAL

Drug: Panobinostat (LBH589), Carboplatin and Paclitaxel

Interventions

Panobinostat (LBH589), Carboplatin and Paclitaxel DRUG

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.

Panobinostat (LBH589), Carboplatin and Paclitaxel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological/cytological diagnosis of solid tumors in which treatment with Carboplatin and Paclitaxel is indicated, e.g. NSCLC, GY tumors, prostate cancer, unknown primary
• Progressive disease (also in terms of tumor markers only, like CA 125 for ovary and PSA for prostate).
• Age 18-75 years
• Prior chemotherapy of ≤ 1 line for advanced disease
• ECOG Performance Status \< 2
• Life expectancy of at least 3 months
• The patient must be able to read, understand and provide written evidence of informed consent
• Female patients may not be pregnant or lactating and must be willing to practice contraception. The effects of LBH589 on the developing human fetus are unknown. For this reason, women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation.
• Male patients that are not surgically sterile must be practicing a medically acceptable contraceptive regimen while on study treatment
• Adequate organ function as defined by the following:
• ANC \> 1500/µL
• Platelets ≥ 100,000/µL
• Haemoglobin ≥ 10 g/dl
• Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 60 ml/min
• Magnesium, potassium and phosphorus ≥ the lower limit of normal or correctable with supplements

You may not qualify if:

• Other chemotherapy treatment \< 4 weeks prior to enrolment
• Hypersensitivity or allergic reactions to platinum compounds or Carboplatin®; hypersensitivity or allergic reactions to Paclitaxel
• Radiotherapy involving \> 30% of the active bone marrow
• Radiotherapy \< 4 weeks prior to enrolment
• Pre-existing peripheral neuropathy ≥ grade 2
• Pre-existing CTCAE hearing loss or tinnitus ≥ grade 2
• Symptomatic pleural effusion
• Clinically significant third space fluid accumulation (e.g. ascites,..)
• Symptomatic brain metastasis or meningeal tumors
• Patients who have not recovered (\> grade 1) from the following toxicities of previous regimens before enrolment: fatigue, mucositis, nausea/vomiting, diarrhea
• Concurrent enrolment, or previous enrolment within 30 days prior to registration in another investigational device or drug trial(s) or is receiving other investigational agent(s)
• Human immunodeficiency virus (HIV) infection
• History of bone marrow or major organ transplant
• Prior high dose treatment with PBSC support
• Impaired cardiac function, including any one of the followings:

Sponsors & Collaborators

• Southern Europe New Drug Organization: lead
• Novartis: collaborator

Study Sites (3)

Huniversitätsspitals Basel

Basel, 4031, Switzerland

Location

Istituto Oncologico della Svizzera Italiana

Bellinzona, 6500, Switzerland

Location

Mèdecin Adjoint, ME - CePO, CHUV

Lausanne, 1011, Switzerland

Location

MeSH Terms

Interventions

Panobinostat; Carboplatin; Paclitaxel

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coordination Complexes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2010
• First Posted: July 9, 2010
• Study Start: June 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: March 1, 2012
• Last Updated: September 13, 2011

Record last verified: 2011-09

Locations

CH (3)