Clinical trial NCT00550277 (phase 2, status: completed)
Conditions: renal cell carcinoma
ICD codes: C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8
Drugs: lbh589
SMILES: [H]\C(=C(\[H])C1=CC=C(CNCCC2=C(C)NC3=CC=CC=C23)C=C1)C(O)=NO
Eligibility criteria:

        Inclusion Criteria:

          -  Histologically documented metastatic or locally unresectable clear cell renal
             carcinoma. In patients with mixed histologies, the clear cell component must comprise
             > 75% of the cancer.

          -  Documented disease progression or intolerance while receiving treatment with: a)
             sunitinib, sorafenib, or both, and b) temsirolimus.

          -  Maximum of 4 prior systemic regimens allowed and may include other targeted agents,
             immunotherapy and chemotherapy.

          -  Measurable disease by RECIST criteria.

          -  ECOG PS 0 or 1.

          -  Laboratory values as follows: ANC >= 1500/μL, Hgb >= 9 g/dL, Platelets >= 100,000/uL,
             AST/SGOT and ALT/SGPT <= 2.5 x ULN or <= 5.0 x ULN in patients with liver metastases,
             Creatinine <= 2.0 mg/dL Or Calculated Creatinine Clearance >= 50 ml/min, Albumin >= 3
             g/dL, Potassium >= lower limit normal (LLN),Phosphorous >= LLN, Calcium >= LLN,
             Magnesium > LLN

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             performed within 7 days prior to start of treatment.

          -  Life expectancy > 12 weeks.

          -  Accessible for treatment and follow-up.

          -  All patients must be able to understand the nature of the study and give written
             informed consent prior to study entry.

        Exclusion Criteria:

          -  Age < 18 years of age.

          -  Prior treatment with an HDAC inhibitor.

          -  Impaired cardiac function

          -  Ongoing therapy with antiarrhythmics or other medications associated with QTc
             prolongation.

          -  Uncorrected hypokalemia or hypomagnesemia.

          -  Uncontrolled hypertension or cardiac arrhythmias.

          -  Active parenchymal brain metastases. Patients who have had brain metastases resected,
             or have received radiation therapy ending > 8 weeks prior to study entry are eligible
             if they meet all of the following criteria: 1) residual neurologic symptoms < grade 1,
             2) no dexamethasone requirement, 3) follow-up MRI shows regression of lesions after
             treatment, with no new lesions appearing.

          -  Active meningeal metastases.

          -  Known diagnosis of human immunodeficiency virus (HIV) infection.

          -  Unresolved diarrhea > CTCAE grade 1.

          -  Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors.

          -  Chemotherapy, investigational drug therapy, major surgery < 4 weeks prior to starting
             study drug or patients that have not recovered from side effects of previous therapy.

          -  Patient is < 5 years free of another primary malignancy except if the other primary
             malignancy is not currently clinically significant or requiring active intervention,
             or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in
             situ. Existence of any other malignant disease is not allowed.

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

          -  Pregnant or breast feeding or female of reproductive potential not using 2 effective
             methods of birth control.

          -  Male patients whose sexual partners are women of childbearing potential not using
             effective birth control.

          -  Patients with gastrointestinal (GI) tract disease, causing the inability to take oral
             medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation,
             prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease.

          -  Other concurrent severe, uncontrolled infection or intercurrent illness

          -  Abnormal thyroid function (TSH or free T4) detected at screening. Patients with known
             hypothyroidism who are stable on thyroid replacement are eligible.