LBH589 Treatment for Refractory Clear Cell Renal Carcinoma

NCT00550277 | Completed Phase 2 Results

• 1 other identifier: SCRI GU 49
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 10

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.

Conditions

Renal Cell Carcinoma

Keywords

Renal Cell Carcinoma; Refractory; LBH589

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Progression-free survival was defined as the interval from the date of first treatment with panobinostat until the date that disease progression or death occurred. Progressive disease (PD): 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm.

  18 months

Secondary Outcomes (2)

• Number of Participants Experiencing ≥Grade 2 Adverse Events

  18 months

• Number of Participants With Overall Response

  18 months

Study Arms (1)

Treatment

OTHER

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.

Drug: LBH589

Interventions

LBH589 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.

Also known as: Panobinostat

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Novartis: collaborator

Study Sites (10)

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

Location

Baton Rouge General Medical Center

Baton Rouge, Louisiana, 70806, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Methodist Cancer Center

Omaha, Nebraska, 68114, United States

Location

Hematology Oncology Associates of Northern NJ

Morristown, New Jersey, 07960, United States

Location

Oncology Hematology Care

Cincinnati, Ohio, 45242, United States

Location

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

Peninsula Cancer Institute

Newport News, Virginia, 23601, United States

Location

Related Publications (1)

• 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.

  PMID: 21696296 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: John D. Hainsworth, MD
• Organization: Sarah Cannon Research Institute

jhainsworth@tnonc.com

615-329-7274

Study Officials

• John D. Hainsworth, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2007
• First Posted: October 29, 2007
• Study Start: January 1, 2008
• Primary Completion: March 1, 2010
• Study Completion: June 1, 2010
• Last Updated: November 23, 2021
• Results First Posted: November 30, 2012

Record last verified: 2021-10

Locations

US (10)