LBH589 Treatment for Refractory Clear Cell Renal Carcinoma

NCT ID: NCT00550277

Last Updated: 2021-11-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2010-06-30

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.

Conditions

Renal Cell Carcinoma

Keywords

Renal Cell Carcinoma; Refractory; LBH589

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

LBH589 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, all patients must begin treatment on a Monday, and continue Monday/Thursday dosing during subsequent treatment cycles. Patients with objective response or stable disease after re-evaluation at week 8 will continue LBH589 at the same dose until disease progression, unacceptable toxicity and/or at the discretion of the investigator.

Group Type: OTHER

LBH589

Intervention Type: DRUG

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.

Interventions

LBH589

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 Type: DRUG

Other Intervention Names

Panobinostat

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

SCRI Development Innovations, LLC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John D. Hainsworth, M.D.

Role: STUDY_CHAIR

SCRI Development Innovations, LLC

Locations

Florida Cancer Specialists

Fort Myers, Florida, United States

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Baton Rouge General Medical Center

Baton Rouge, Louisiana, United States

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States

Methodist Cancer Center

Omaha, Nebraska, United States

Hematology Oncology Associates of Northern NJ

Morristown, New Jersey, United States

Oncology Hematology Care

Cincinnati, Ohio, United States

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, United States

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Peninsula Cancer Institute

Newport News, Virginia, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 21696296 (View on PubMed)

Other Identifiers

SCRI GU 49

Identifier Type: -

Identifier Source: org_study_id