Clinical trial NCT01115036 (phase 2, status: withdrawn)
Conditions: recurrent glioblastoma
ICD codes: G47.13, J01.41, K11.22, K12.0, N96, F33.8, G03.2
Drugs: panobinostat
SMILES: [H]\C(=C(\[H])C1=CC=C(CNCCC2=C(C)NC3=CC=CC=C23)C=C1)C(O)=NO
Reason stopped: 
    no subjects were enrolled on this study, so study was closed and ind withdrawn.
  
Eligibility criteria:

        Inclusion Criteria:

          -  Patient age is ≥ 18 years

          -  Histologically-confirmed grade 4 malignant glioma patients;

          -  Candidate for surgical resection of tumor;

          -  No more than 3 prior episodes of progressive disease;

          -  An interval of at least 4 weeks between prior surgical resection or two weeks from
             stereotactic biopsy;

          -  An interval of at least 12 weeks from the end of prior radiotherapy unless there is a
             new area of enhancement consistent with recurrent tumor outside of the radiation
             field, or there are progressive changes on MRI on at least two consecutive MRI scans
             at least four weeks apart, or there is biopsy-proven tumor progression;

          -  An interval of at least 4 weeks from prior chemotherapy (6 weeks for nitrosoureas) or
             investigational agent, unless the patient has recovered from all anticipated
             toxicities associated with that therapy;

          -  Karnofsky * 70%;

          -  Hemoglobin ≥ 9 g/dL, ANC > 1,500 cells/*l, platelets > 150,000 cells/*l ;

          -  Serum creatinine < 1.5 mg/dl or 24-hour creatinine clearance ≥ 50 ml/min, serum SGOT
             and bilirubin < 1.5 times upper limit of normal; total serum calcium (corrected for
             serum albumin) or ionized calcium ≥ LLN; serum potassium ≥ LLN; serum sodium ≥ LLN;
             serum albumin ≥ LLN or 3g/dl;

          -  Clinically euthyroid (Note: Patients are permitted to receive thyroid hormone
             supplements to treat underlying hypothyroidism);

          -  Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional
             normal;

          -  Ability to provide written informed consent obtained prior to participation in the
             study and any related procedures being performed;

        Exclusion Criteria:

          -  Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer

          -  Patients who will need valproic acid for any medical condition during the study or
             within 5 days prior to first panobinostat treatment;

          -  Use of CYP-3A inducing anti-epileptics (phenytoin, fosphenytoin, carbamazepine,
             oxcarbazepine, phenobarbitol, primidone);

          -  Pregnancy or breast feeding;

          -  Co-medication that may interfere with study results; e.g. immuno-suppressive agents
             other than corticosteroids;

          -  Active infection requiring intravenous antibiotics;

          -  Prior bevacizumab within 6 weeks of study enrollment;

          -  Therapeutic anti-coagulation with warfarin, aspirin, non-steroidal anti-inflammatory
             drugs or clopidogrel;

          -  Impaired cardiac function including any one of the following:

               -  Complete left bundle branch block or use of a permanent cardiac pacemaker,
                  congenital long QT syndrome, history or presence of ventricular tachyarrhythmias,
                  clinically significant resting bradycardia (<50 beats per minute), QTcF > 450
                  msec on screening ECG, or right bundle branch block + left anterior hemiblock
                  (bifascicular block);

               -  Presence of atrial fibrillation (ventricular heart rate >100 bpm);

               -  Previous history angina pectoris or acute MI within 6 months;

               -  Congestive heart failure (New York Heart Association functional classification
                  III-IV) or baseline MUGA/Echo shows LVEF < 45%;

          -  Uncontrolled hypertension;

          -  Concomitant use of drugs with a risk of causing Torsades de pointes (See Table 14-1);

          -  Patients with unresolved diarrhea ≥ grade 2;

          -  Patients with ≥ grade 2 peripheral neuropathy;

          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly
             alter the absorption of oral panobinostat (e.g., ulcerative disease, uncontrolled
             nausea, vomiting, diarrhea, malabsorption syndrome, obstruction, or stomach and/or
             small bowel resection)

          -  Other concurrent severe and/or uncontrolled medical conditions;

          -  Concomitant use of any anti-cancer therapy or radiation therapy;

          -  Patients with a history of another primary malignancy within 5 years other than
             curatively treated carcinoma in situ of the cervix, or basal or squamous cell
             carcinoma of the skin;

          -  Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C;
             baseline testing for HIV and hepatitis C is not required;

          -  Patients with any significant history of non-compliance to medical regimens or with
             inability to grant a reliable informed consent.

          -  Women of childbearing potential (WOCBP) not willing to use a double barrier method of
             contraception during the study and 3 months after the end of treatment. One of these
             methods of contraception must be a barrier method. WOCBP are defined as sexually
             mature women who have not undergone a hysterectomy or who have not been naturally
             postmenopausal for at least 12 consecutive months (i.e., who has had menses any time
             in the preceding 12 consecutive months). Women of childbearing potential (WOCBP) must
             have a negative serum pregnancy test within 7 days of the first administration of oral
             panobinostat;

          -  Male patients whose sexual partners are WOCBP not using a double method of
             contraception during the study and 3 months after the end of treatment. One of these
             methods must be a condom.