Basic Trial Information
Trial Description
     Summary
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Active 18 and over Other SCRI GU 49 IND 79,340, NCT00550277

Trial Description

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.

Eligibility Criteria

Inclusion Criteria:

1. 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.

2. Documented disease progression or intolerance while receiving treatment with: a) sunitinib, sorafenib, or both, and b) temsirolimus.

3. Maximum of 4 prior systemic regimens allowed and may include other targeted agents, immunotherapy and chemotherapy.

4. Measurable disease by RECIST criteria.

5. ECOG PS 0 or 1.

6. 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

7. Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment.

8. Life expectancy > 12 weeks.

9. Accessible for treatment and follow-up.

10. All patients must be able to understand the nature of the study and give written informed consent prior to study entry.

Exclusion Criteria:

1. Age < 18 years of age.

2. Prior treatment with an HDAC inhibitor.

3. Impaired cardiac function including any of the following:

• Screening ECG with a QTc > 450 msec.

• Congenital long QT syndrome.

• History of sustained ventricular tachycardia.

• Any history of ventricular fibrillation or torsades de pointes.

• Bradycardia defined as heart rate < 50 beats per minutes. Patients with a pacemaker and heart rate > 50 beats per minute are eligible.

• Myocardial infarction or unstable angina within 6 months of study entry.

• Congestive heart failure (NY Heart Association class III or IV [See Appendix B]).

• Right bundle branch block and left anterior hemiblock (bifasicular block).

• Previous high cumulative dose anthracycline therapy (i.e. doxorubicin >300 mg/m2 or equivalent).

4. Ongoing therapy with antiarrhythmics or other medications associated with QTc prolongation.

5. Uncorrected hypokalemia or hypomagnesemia.

6. Uncontrolled hypertension (systolic blood pressure [BP] >180 or diastolic BP >100mm Hg) or uncontrolled cardiac arrhythmias.

7. 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.

8. Active meningeal metastases.

9. Known diagnosis of human immunodeficiency virus (HIV) infection.

10. Unresolved diarrhea > CTCAE grade 1.

11. Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors.

12. 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.

13. 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.

14. Concomitant use of any anti-cancer therapy or radiation therapy.

15. Pregnant or breast feeding or female of reproductive potential not using 2 effective methods of birth control.

16. Male patients whose sexual partners are women of childbearing potential not using effective birth control.

17. 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 (e.g., Crohn's Disease, ulcerative colitis).

18. Other concurrent severe, uncontrolled infection or intercurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

19. Abnormal thyroid function (TSH or free T4) detected at screening. Patients with known hypothyroidism who are stable on thyroid replacement are eligible.

Trial Contact Information

Trial Lead Organizations/Sponsors

Sarah Cannon Research Institute

John D. Hainsworth, M.D.

Study Chair

John D. Hainsworth, M.D.		Ph: (615) 329-7274
		Email: jhainsworth@tnonc.com

Trials Info		Ph: (615) 329-7274
		Email: trialsinfo@scresearch.net

U.S.A.
Florida
	Fort Myers
	Florida Cancer Specialists - Fort Myers Broadway
		Katie Goodman	Ph: 239-274-9930
			Email: KatieG@flcancer.com
Ohio
	Cincinnati
	Oncology Hematology Care, Incorporated - Blue Ash
		Research Program Coordinator	Ph: 513-891-4800
			Email: contact@ohcmail.com
Tennessee
	Chattanooga
	Chattanooga Oncology and Hematology Associates
		Research Coordiantor	Ph: 423-698-1844
			Email: research@cohaonline.com
	Nashville
	Tennessee Oncology, PLLC - Baptist Medical Building

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00550277
Information obtained from ClinicalTrials.gov on September 03, 2008