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An Open-label, Uncontrolled Phase II Trial of HDAC-Inhibitor LBH589 in Patients With Chemo-refractory Metastatic Gastric Cancer Overexpressing Histone Deacetylases (HDACs) - CLBH589BDE03T

Phase 2
18 Years
90 Years
Not Enrolling
Metastatic Gastric Cancer

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Trial Information

An Open-label, Uncontrolled Phase II Trial of HDAC-Inhibitor LBH589 in Patients With Chemo-refractory Metastatic Gastric Cancer Overexpressing Histone Deacetylases (HDACs) - CLBH589BDE03T

Inclusion Criteria:

1. Male and female patients aged 18 - 90 years

2. Signed and dated informed consent of the patient before the start of specific
protocol procedures

3. Histologically proven adenocarcinoma of stomach, esophagogastric junction or lower
esophagus (Barrett carcinoma)

4. Measurable metastatic disease according to the RECIST (33). If locally recurrent
disease, it must be associated with at least one measurable lymph node (> 20 mm by CT
scan or > 10 mm with spiral CT)

5. Overexpression of at least one class I HDAC in the cancer biopsy as assessed by

6. Failure of prior palliative chemotherapy/chemotherapies (at least one Irinotecan- or
Cisplatin-based). Failure is defined either by progression of disease or by
significant toxicity that precludes further treatment

7. At least 4 weeks from previous chemotherapy at first dose of trial drug

8. Resolution of all acute toxic side effects of prior therapy or surgical procedures to
grade ≤ 1 NCI-CTC (except for the laboratory values)

9. Adequate organ function as defined by the following criteria:

- Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase
[SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase
[SGPT]) ≤ 2.5 x upper limit of normal (ULN), or AST and ALT ≤ 5 x ULN if liver
function abnormalities are due to underlying malignancy

- Total serum bilirubin ≤ 1.5 x ULN

- Absolute neutrophil count (ANC) ≥ 1500/µL

- Platelets ≥ 100,000/µL

- Hemoglobin ≥ 8.0 g/dL without support of growth factors (previous administration
of erythrocyte concentrate is allowed)

- Calculated CrCl ≥ 50 mL/min (MDRD Formula)

- Serum calcium ≤ 12.0 mg/dL

- Serum creatinine ≤ 2.0 x ULN

- Lipase/Amylase ≤ 2,5 x ULN

- All other laboratory values specified in chapter 7.5: resolution of all side
effects of prior therapy or surgical procedure to grade < 3 NCI CTC

10. At least 4 weeks from any major surgery (at first dose of trial drug)

11. Karnofsky Performance Status (KPS) > 70

12. Life expectancy > 12 weeks

13. Patients must be able to swallow LBH589 capsules

14. Patients who understand the nature of the trial and are willing and able to comply
with scheduled visits, treatment plans, laboratory tests and other trial procedures

15. Female patients who are capable of bearing children must have a negative pregnancy
test result (serum or urine) at trial entry. All women included in the trial must be
surgically sterile or postmenopausal or agree to employ adequate birth control
measures for the duration of the trial and six months post-dosing. Male patients must
be surgically sterile or must agree to use effective contraception during the trial
and six months post-dosing

Exclusion Criteria:

1. Other tumor type than adenocarcinoma (e.g., leiomyosarcoma, lymphoma) or a second
cancer except in patients with squamous or basal cell carcinoma of the skin or
carcinoma in situ of the cervix which has been effectively treated. Patients
curatively treated and disease free for at least 5 years will be discussed with the
sponsor before inclusion

2. Patients with known brain or leptomeningeal metastasis

3. Intake of non-permitted concomitant drugs (the coordinating investigator should be
contacted to discuss the individual case), see chapter 5.4:

- Concomitant treatment with antiarrhythmics and drugs with dysrhythmic potential
(ie, terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol,
bepridil, haloperidol, risperidone, and indapamide)

- Prior exposure to a HDAC inhibitor compound

- Administration of potent CYP34A inhibitors during or within 7 days before start
of LBH589-treatment (e.g. ketoconazole, itraconazole, clarithromycin,
erythromycin, diltiazem, verapamil, delavirdine, indinavir, saquinavir,
ritonavir, atazanavir, nelfinavir, grapefruit juice)

- Administration of potent CYP3A4 inducers during or within 12 days before start
of LBH589-treatment (e.g. dexamethasone, rifampicin, rifabutin, carbamazepine,
phenobarbital, phenytoin, St. John´s wort, efavirenz, tipranavir)

- Ongoing treatment with therapeutic doses of anticoagulants such as Coumadin or
heparins (however, low dose Coumadin up to 2 mg PO daily for deep vein
thrombosis prophylaxis is allowed)

- Any other medicinal anticancer therapy during treatment phase except treatment
with non-conventional therapies (e.g. herbs or acupuncture) and vitamins/mineral
supplements, provided that they do not interfere with the trial endpoint, in the
opinion of the investigator

- Concurrent systemic immune therapy, chemo- or hormone therapy

- Concomitant or within a 4-week period administration (from first dose of trial
drug) of any other experimental drug under investigation) and participation in
another clinical trial

4. Any prior radiotherapy of target lesions

5. Bowel obstruction, history or presence of inflammatory enteropathy or extensive
intestinal resection (> hemicolectomy or extensive small intestine resection with
chronic diarrhea), Crohn's disease, ulcerative colitis

6. Current history of chronic diarrhea and/or diarrhea > CTCAE grade 3

7. Active disseminated intravascular coagulation, or patients prone to thromboembolism

8. Known human immunodeficiency virus (HIV) infection

9. Active uncontrolled infection

10. Other severe acute or chronic medical or psychiatric condition, or laboratory
abnormality that would impart, in the judgment of the investigator, excess risk
associated with trial participation or trial drug administration, or which, in the
judgment of the investigator, would make the patient inappropriate for entry into the

11. Known allergic/hypersensitivity reaction to any of the components of the treatment;
or known drug abuse/alcohol abuse

12. Impaired cardiac function or clinically significant cardiac diseases, including any
one of the following:

- Known history of QT interval prolongation, ongoing QT prolongation (> 450 msec
for males or > 470 msec for females), any cardiac ventricular dysrhythmias,
atrial fibrillation of any grade

- History or presence of sustained ventricular tachyarrhythmia. (Patients with a
history of atrial arrhythmia are eligible but should be discussed with the
Sponsor prior to enrollment)

- Any history of ventricular fibrillation or torsade de pointes

- Bradycardia defined as HR < 50 bpm. Patients with pacemakers are eligible if HR
≥ 50 bpm.

- Screening ECG with a QTc > 450 msec

- Right bundle branch block + left anterior hemiblock (bifascicular block)

- Patients with myocardial infarction or unstable angina ≤ 6 months prior to
starting study drug

- Other clinically significant heart disease (e.g., CHF NY Heart Association class
III or IV , uncontrolled hypertension, history of labile hypertension, or
history of poor compliance with an antihypertensive regimen)

13. Patients who have received steroids (e.g. dexamethasone) ≤ 2 weeks prior to starting
study treatment or who have not recovered from side effects of such therapy.
Concomitant therapy medications that include corticosteroids are allowed if patients
receive < 10 mg of prednisone or equivalent as indicated for other medical
conditions, or up to 100 mg of hydrocortisone as pre-medication for administration of
certain medications or blood products while enrolled in this study.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

objective response rate within the first six treatment cycles

Outcome Description:

objective response rate (CR + PR) within the first six treatment cycles

Principal Investigator

Martina Mayr, Dr.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Klinikum rechts der Isar


Germany: Ethics Commission

Study ID:




Start Date:

June 2009

Completion Date:

Related Keywords:

  • Metastatic Gastric Cancer
  • Stomach Neoplasms