Trial 3C-08-1

Phase I Clinical Trial with LBH589 and Infusional 5-FU/LV in Patients with Metastatic Colorectal Cancer who Failed 5-FU Based Chemotherapy.

Type: Cancer Therapy
Phase: Phase I
Status: Open to Accrual
Treatments: Chemotherapy: Systemic
Randomized: No
Defintions of terms and FAQ about clinical trials.

Trial Leaders/Researchers: Heinz Josef Lenz, M.D.
Other Trial Staff: Ramona Lujan, R.N., Jiayi Jiang, D.M., Jennifer Berg, D.M.

Staff may log in to see study documents.

You may participate in this study if:

	Requirement
1	Histologically or cytologically confirmed advanced/metastatic colorectal cancer
2	Measurable disease
3	Must have received prior therapy (in any setting) with 5-FU, CPT-11, and oxaliplatin. Patients may have received prior erbitux and bevacizumab, but it is not required.
4	Must have received at least one prior chemotherapy regimen for advanced disease
5	Tumor must be accessible for core biopsy at the beginning of treatment and patients have a high intra-tumoral TS expression level prior to the beginning of treatment
6	At least 18 years of age
7	Life expectancy of >12 weeks
8	ECOG performance status 0-2 (Karnofsky >50%)
9	WBC = / > 3.0; AGC = / > 1.5; platelets = / > 100,000; Hgb = / > 9.0
10	SGOT and SGPT < / = 2.5 x uln (< / = 5 x uln if transaminase elevation due to liver mets); bilirubin < / - 1.5 x uln
11	Creatinine < / = 1.5 x uln or 24-hr CrCl = / > 50 ml/min
12	Potassium = / > LLN; phosphorus = / > LLN; calcium = / > LLN; Mg = / > LLN; albumin = / > 3 gm/dl
13	TSH and free T4 wnl (may be on thyroid hormone replacement)
14	INR < / = 1.5 x uln unless receiving therapeutic anti-coagulation
15	Baseline MUGA must demonstrate LVEF = / > LLN
16	Clinically euthyroid. Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
17	Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of LBH589 will be determined following review by the PI.
18	Signed an approved study-specific informed consent and HIPAA

You may not participate in this study if:

1	Previously received other investigational agent within 28 days of study entry. Patients who have received chemotherapy, any investigational drug, or undergone major surgery <4 weeks prior to starting study drug, or who have not recovered from side effects of such therapy.
2	Planning to receive other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study
3	Known brain metastases
4	History of allergic reactions attributed to compounds of similar chemical or biologic composition to LBH589. These compounds include sodium butyrate, trichostatin A (TSA), trapoxin (TPX), MS-27-275 and depsipeptide.
5	Severe and/or uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic CHF, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
6	Pregnant or breastfeeding females. Female patients of reproductive potential must use two adequate barrier methods of contraception or must abstain from heterosexual activity throughout the study and for 30 days after the last dose of study medication. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of oral LBH589. Male patients whose sexual partners are WOCBP must use an adequate method of contraception for the duration of the study, and for 30 days after the last dose of study medication.
7	History of another primary malignancy within 5 years other than curatively treated CIS of the cervix, or basal or squamous cell carcinoma of the skin.
8	Unresolved diarrhea > Gr 1
9	Acute infection requiring iv antibiotics, anti-viral or anti-fungal medications within 2 weeks prior to the start of study drugs
10	Known positivity for HIV or hepatitis C; baseline testing for HIV and hepatitis C is not required.
11	Impaired cardiac function including any one of the following: [a] Screening ECG with a QTc >450 msec; [b] congenital long QT syndrome; [c] History of sustained ventricular tachycardia; [d] Any history of ventricular fibrillation or torsades de pointes; [e] Bradycardia <50/min. Patients with a pacemaker and HR = / > 50/min are eligible. [f] MI or unstable angina within 6 mos of study entry; [g] CHF NYHA Class III or IV); [h] RBBB and left anterior hemiblock (bifasicular block).
12	Prior cancer treatment with an HDAC inhibitor (e.g., vorinostat, Depsipeptide, MS-275, LAQ-824, PXD-101, and valproic acid)
13	Uncontrolled HTN
14	Concomitant use of drugs with a risk of causing torsades de pointes
15	Any significant history of non-compliance to medical regimens
16	Impairment of GI function or GI disease that may significantly alter absorption of oral panobinostat (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, obstruction, or stomach and/or small bowel resection)
17	Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589

For further information on a study, please contact the Clinical Investigation Support Office at (323) 865-0451, or clinical.trials@med.usc.edu.

To schedule a consultation with the hospital, please call our New Patient Referrals Office at (323) 865-3111.