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Advanced Solid TumorsPhase 1NCT01159418

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

A Phase 1 study testing Panobinostat (LBH589), Carboplatin and Paclitaxel in people with Advanced Solid Tumors, run by Southern Europe New Drug Organization at 3 sites in Switzerland.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Advanced Solid Tumors
What is being tested?
Panobinostat (LBH589), Carboplatin and Paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
3 sitesSwitzerland
Study dates
Jun 2008to Mar 2012
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 2.5 x ULN or ≤ 5.0 x ULN if hepatic involvement is present
  • Serum bilirubin ≤ 1.5 x ULN
  • Alkaline phosphatase (ALP) ≤ 2.5 x ULN or ALP > 2.5 x UNL with liver fraction ≤ 2.5 x ULN

Who cannot join

  • 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
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  • 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:
  • Complete Left Bundle Branch Block or obligate use of a cardiac pacemaker or congenital long QT syndrome or history or presence of atrial or ventricular tachyarrhythmias or clinically significant resting bradycardia (< 50 beats per minute) or QTcF > 480 msec on screening ECG or Right Bundle Branch block + left anterior hemiblock (bifascicular block)
  • Angina pectoris or acute MI ≤ 3 months prior to starting study drug
  • Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, malabsorption syndrome, or small bowel resection)
  • Acute or chronic liver or renal disease
  • Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease) that could cause unacceptable safety risks or compromise compliance with the protocol
  • Concomitant use of CYP3A4/5 inhibitors or inducers where the treatment can not be discontinued or switched to a different medication prior to starting study drug (medications listed in Appendix 3). The medications listed in Appendix 3 have a relative risk of prolonging the QT interval or inducing Torsades de Pointes, but do not represent an exclusion criteria
  • Treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GMCSF) ≤ 2 weeks prior to starting study drug.
  • Treatment with therapeutic doses of sodium warfarin (Coumarin ). Low doses of Coumarin (e.g., ≤ 2 mg/day) for line patency is allowable
  • Patients who have received biologic therapy (excluding antiangiogenics) or immunotherapy ≤ 2 weeks prior to starting study treatment or who have not recovered from side effects of such therapy
  • Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Unable or unwilling to comply with all study procedures
  • Current history of alcohol or drug abuse

Trial locations and contacts

3 sites in 1 country.

Switzerland3 sites

  • Huniversitätsspitals Basel

    Basel, 4031

  • Istituto Oncologico della Svizzera Italiana

    Bellinzona, 6500

  • Mèdecin Adjoint, ME - CePO, CHUV

    Lausanne, 1011

Other trials in Switzerland

About this study

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

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.

Read the 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.

Being tested
Panobinostat (LBH589), Carboplatin and Paclitaxel
Keywords
solid tumors, Panobinostat, histone deacetylase inhibitors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Panobinostat (LBH589), Carboplatin and PaclitaxelDrug

    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.

Study groups in NCT01159418
Study groupRoleWhat they receive
Panobinostat (LBH589), Carboplatin and PaclitaxelExperimentalNot described
Receives: Drug: Panobinostat (LBH589), Carboplatin and Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) Recommended Dose (RD)

    Number of Dose-Limiting Tocixities (DLTs)

    Measured: 3 weeks after the first drug administration (1 Cycle)

Secondary outcomes (3)

  1. Hints of antitumor activity

    objective tumor responses based on RECIST criteria

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

  2. Biomarkers of HDAC

    acetylation of histones, H3, H4 and tubulin in PBMC

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

  3. Safety and tolerability

    AE types and frequency monitored by laboratory and instrumental assessments, and physical examination

    Measured: 4 weeks after last drug administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jul 2010 (estimated)
  2. Study startJun 2008
  3. Primary completionDec 2011 (estimated)
  4. Study completionMar 2012 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01159418
Sponsor's protocol ID
SKSD00702
Status last verified
Sep 2011
First submitted
8 Jul 2010
Last updated
13 Sep 2011
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Panobinostat (LBH589), Carboplatin and Paclitaxel in people with Advanced Solid Tumors, run by Southern Europe New Drug Organization at 3 sites in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 13 Sep 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) Recommended Dose (RD) (time frame: 3 weeks after the first drug administration (1 Cycle)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01159418.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2011.

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