Clinical trial NCT00550277: LBH589 Treatment for Refractory Clear Cell Renal Carcinoma
Official title: A Phase II Study of LBH589 in the Treatment of Patients With Refractory Clear Cell Renal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Renal Cell Carcinoma
Keywords: Renal Cell Carcinoma
Refractory
LBH589
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2007-10-29
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: Inhibition of histone deacetylase (HDAC) provides a potential target for cancer treatment. Histones are components of the core proteins of nucleosomes, and acetylation and deacetylation of these proteins play a role in the regulation of gene expression. HDAC activity is known to be increased in many types of malignant cells; HDAC inhibitors have been shown to induce differentiation, cell cycle arrest, and apoptosis in cultured tumor cells. Since this tumor-associated mechanism is common to many types of cancer, HDAC may have a broad role in cancer treatment.

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.

Primary outcomes:
measure: Progression-free Survival
timeFrame: 18 months
Secondary outcomes:
measure: Number of Participants Experiencing ≥Grade 2 Adverse Events
timeFrame: 18 months
measure: Number of Participants With Overall Response
timeFrame: 18 months
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Baton Rouge
country: United States
facility: Baton Rouge General Medical Center
state: Louisiana
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Omaha
country: United States
facility: Methodist Cancer Center
state: Nebraska
city: Morristown
country: United States
facility: Hematology Oncology Associates of Northern NJ
state: New Jersey
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Chattanooga
country: United States
facility: Chattanooga Oncology Hematology Associates
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Newport News
country: United States
facility: Peninsula Cancer Institute
state: Virginia
Study officials:
affiliation: SCRI Development Innovations, LLC
name: John D. Hainsworth, M.D.
role: STUDY_CHAIR
References:
citation: Hainsworth JD, Infante JR, Spigel DR, Arrowsmith ER, Boccia RV, Burris HA. A phase II trial of panobinostat, a histone deacetylase inhibitor, in the treatment of patients with refractory metastatic renal cell carcinoma. Cancer Invest. 2011 Aug;29(7):451-5. doi: 10.3109/07357907.2011.590568. Epub 2011 Jun 22.