A Phase II Study of LBH589 in the Treatment of Patients With Refractory Clear Cell Renal Carcinoma
- 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.
- Age < 18 years of age.
- Prior treatment with an HDAC inhibitor.
- Impaired cardiac function
- Ongoing therapy with antiarrhythmics or other medications associated with QTc
- 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.