Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00550277
Other study ID # SCRI GU 49
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date January 2008
Est. completion date June 2010

Study information

Verified date October 2021
Source SCRI Development Innovations, LLC
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 20
Est. completion date June 2010
Est. primary completion date March 2010
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Intervention

Drug:
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.

Locations

Country Name City State
United States Baton Rouge General Medical Center Baton Rouge Louisiana
United States Center for Cancer and Blood Disorders Bethesda Maryland
United States Chattanooga Oncology Hematology Associates Chattanooga Tennessee
United States Oncology Hematology Care Cincinnati Ohio
United States Florida Cancer Specialists Fort Myers Florida
United States Northeast Georgia Medical Center Gainesville Georgia
United States Hematology Oncology Associates of Northern NJ Morristown New Jersey
United States Tennessee Oncology, PLLC Nashville Tennessee
United States Peninsula Cancer Institute Newport News Virginia
United States Methodist Cancer Center Omaha Nebraska

Sponsors (2)

Lead Sponsor Collaborator
SCRI Development Innovations, LLC Novartis

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Number of Participants Experiencing =Grade 2 Adverse Events An adverse event (AE) is the development of an undesirable medical condition, or the deterioration of a preexisting medical condition (other than the condition that is being treated by the trial) following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. The number of participants experiencing such adverse events that are related to the study drug are reported here. 18 months
Secondary Number of Participants With Overall Response Response was evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Overall response is defined as the proportion of participants whose disease either decreased (partial response- PR) or disappeared (Complete response - CR).
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD
18 months
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04987203 - Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma Phase 3
Recruiting NCT06391879 - Establishment of a Multidimensional Prediction Model for the Natural Course of VHL Disease-related Renal Cell Carcinoma
Completed NCT02526017 - Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers Phase 1
Recruiting NCT05059444 - ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation
Terminated NCT03655613 - APL-501 or Nivolumab in Combination With APL-101 in Locally Advanced or Metastatic HCC and RCC Phase 1/Phase 2
Active, not recruiting NCT03170960 - Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors Phase 1/Phase 2
Withdrawn NCT05418387 - A Social Support Intervention to Improve Treatment Among Hispanic Kidney and Liver Cancer Patients in Arizona N/A
Recruiting NCT04623502 - An Investigation of Kidney and Urothelial Tumor Metabolism in Patients Undergoing Surgical Resection and/or Biopsy N/A
Completed NCT02853344 - Study of Pembrolizumab (MK-3475) Monotherapy in Locally Advanced/Metastatic Renal Cell Carcinoma (MK-3475-427/KEYNOTE-427) Phase 2
Terminated NCT04088500 - A Study of Combination Nivolumab and Ipilimumab Retreatment in Patients With Advanced Renal Cell Carcinoma Phase 2
Completed NCT05070637 - Circulating Tumor Cell Reducing No-touch Nephrectomy N/A
Active, not recruiting NCT03634540 - A Trial of Belzutifan (PT2977, MK-6482) in Combination With Cabozantinib in Patients With Clear Cell Renal Cell Carcinoma (ccRCC) (MK-6482-003) Phase 2
Not yet recruiting NCT06049030 - A Study of HS-10516 in Patients With Advanced Clear Cell Renal Cell Carcinoma Phase 1
Completed NCT03652077 - A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies Phase 1
Completed NCT01358721 - Phase I Biomarker Study (BMS-936558) Phase 1
Active, not recruiting NCT04503148 - Anesthesia and Cancer Study: Renal Cell Carcinoma N/A
Completed NCT02386826 - INC280 Combined With Bevacizumab in Patients With Glioblastoma Multiforme Phase 1
Not yet recruiting NCT05808608 - A Study of AK104 Plus Axitinib in Advanced/Metastatic Special Pathological Subtypes of Renal Cell Carcinoma Phase 1/Phase 2
Withdrawn NCT03323710 - Study of Propranolol Plus Sunitinib in First-line Treatment of Metastatic Renal Cell Carcinoma Phase 2
Not yet recruiting NCT02787915 - DC1s-CTL Cellular Therapy for Renal Cell Carcinoma Phase 1/Phase 2