Histone Deacetylases - Gastric Cancer (HDAC-GaCa-2008)

NCT01528501 | Terminated Phase 2

• 1 other identifier: CLBH589BDE03T
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label, phase II trial evaluating the antitumor activity and safety of the oral Histone Deacetylase (HDAC)-Inhibitor LBH589. The treatment consists of 20 mg LBH589 three times a week in patients with chemo-refractory HDAC overexpressing. metastatic adenocarcinoma of stomach, esophagogastric junction or lower esophagus (Barrett carcinoma). One cycle lasts 21 days. A total of 28 patients will be enrolled in this trial. In patients experiencing LBH589-related toxicity requiring treatment rest or dose reduction dose may be reduced. Subsequent dose adjustment will be permitted based on outcome. Treatment will continue until disease progression or intolerable adverse events. Subsequently, the patients will be followed-up for one year.

Conditions

Metastatic Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• objective response rate within the first six treatment cycles

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

Secondary Outcomes (4)

• Progression free survival (PFS)

• 1-year survival

• Overall survival

• Safety and tolerability of LBH 589

Study Arms (1)

I

EXPERIMENTAL

Drug: Panobinostat (LBH589)

Interventions

Panobinostat (LBH589) DRUG

I

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients aged 18 - 90 years
• Signed and dated informed consent of the patient before the start of specific protocol procedures
• Histologically proven adenocarcinoma of stomach, esophagogastric junction or lower esophagus (Barrett carcinoma)
• 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)
• Overexpression of at least one class I HDAC in the cancer biopsy as assessed by immunohistochemistry
• 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
• At least 4 weeks from previous chemotherapy at first dose of trial drug
• Resolution of all acute toxic side effects of prior therapy or surgical procedures to grade ≤ 1 NCI-CTC (except for the laboratory values)
• 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)

You may not qualify if:

• Patients with known brain or leptomeningeal metastasis
• 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
• Any prior radiotherapy of target lesions
• 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
• Current history of chronic diarrhea and/or diarrhea \> CTCAE grade 3
• Active disseminated intravascular coagulation, or patients prone to thromboembolism
• Known human immunodeficiency virus (HIV) infection

Sponsors & Collaborators

• Technical University of Munich: lead
• Novartis: collaborator

Study Sites (2)

Klinikum rechts der Isar

Munich, Bavaria, 81675, Germany

Location

Universitätsklinikum Mannheim

Mannheim, 68167, Germany

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Martina Mayr, Dr.

  Klinikum rechts der Isar

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2012
• First Posted: February 8, 2012
• Study Start: June 1, 2009
• Primary Completion: February 1, 2013
• Last Updated: May 1, 2013

Record last verified: 2012-12

Locations

DE (2)