LBH589 Treatment for Refractory Clear Cell Renal Carcinoma
Condition: Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms
Intervention: LBH589
Intervention description: LBHLBH589 will be administered orally at a dose of 45 mg (1 - 5 mg capsule and 2 - 20 mg capsules) on Monday and Thursday of each week (twice weekly). To enable patients to undergo cardiac monitoring (Section 3.5.2), all patients must begin treatment on a Monday, and continue Monday/Thursday dosing during subsequent treatment cycles.
Intervention MeSH terms: Panobinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Renal Cell Carcinoma; Refractory; LBH589

Summary:

      Inhibition of histone deacetylase (HDAC) provides a novel approach for cancer treatment.
      LBH589, an oral HDAC inhibitor, has been well tolerated in phase I trials and has shown
      activity against several types of cancer. In this nonrandomized phase II trial, we are
      investigating the activity of LBH589 in the treatment of patients with refractory clear cell
      renal carcinoma.
    

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.