| | Requirement |
| 1 | Bippsy-proven advanced solid tumor for Group D or biopsy-proven Hepatocellular carcinoma (HCC) for Groups A, B, C, E & F.
Archived tissue samples will be collected.
|
| 2 | Patients without biopsy-proven HCC must meet all 3 criteria below: a) Bi-dimensionally measurable disease 2 cm or greater, by enhanced spiral CT or MRI. b)Serology (+) for Hep B or C
c) a-fetoprotein > 400 mg/L
|
| 3 | Fibrolamellar histology is allowed if considered not appropriate for surgical resection based on tumor size, extra hepatic involvement, or multiple lobe involvement. |
| 4 | Patient should not be appropriate for curative surgical resection. |
| 5 | Concurrent assignment to a transplantation list is allowed. |
| 6 | Prior chemotherapy & liver-directed therapy (e.g. RFA , chemo-embolization, etc.) are allowed provided there is evidence of disease progression since treatment & the following criteria are met:
a)Toxicity must have resolved, returned to baseline or been deemed irreversible & documented in patient medical record.
b) At least 4 wks since last chemotherapy, immunotherapy, radiotherapy, anti-cancer hormonal therapy, or targeted therapy (e.g. sorafenib) prior to protocol treatment (at least 6 wks for Avastin & nitrosoureas)
|
| 7 | Patients with biliary stent are eligible provided stent has been in place for at least 10 days prior to 1st dose & hepatic function has stabilized (2 measurements at least 2 days apart that put patient in same hepatic dysfunction stratum will be accepted as evidence of stable hepatic function). |
| 8 | 4 wks since any prior major surgery. |
| 9 | ECOG Performance Status 0-3. |
| 10 | ANC 1500 or higher; Platelets 80,000 or higher; Hgb 9.0 or higher. |
| 11 | Adequate hepatic function for Group D:Total bilirubin equal to (or less than) ULN (except for known Gilbert’s syndrome); AST &/or ALT 1.5 (or less) x ULN; Serum albumin > 3.5; INR 1.8 (or less) x ULN
|
| 12 | Creatinine 2.0 or less OR CrCl 45 mL/min or higher, by Cockcroft -Gault formula. |
| 13 | Screening BP < 150/100. |
| 14 | LVEF 45% or higher on baseline ECHO. |
| 15 | 18 y/o and above. |
| 16 | Women of child-bearing potential must have (-) serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hrs prior to tretament & before start of each continuous cycle of treatment. |
| 17 | Women of child-bearing potential must use adequate method of contraception throughout the study & for up to 12 weeks after the study. |
| 18 | Signed Informed Consent (including HIPAA authorization). |
| 1 | Women of child-bearing potential unwilling or unable to use acceptable method of contraception during the study & for up to 12 wks after the study or using a prohibited contraceptive method such as only spermicidal/barrier method. |
| 2 | Pregnant or breastfeeding females. |
| 3 | For sites also participating in primary HCC Protocol CA182006, patient must be deemed ineligible for that study to participate in this trial. |
| 4 | Portal-systemic encephalopathy with clinical Gr > 2. |
| 5 | Evidence of portal hypertension. |
| 6 | Prior variceal bleed permitted if patient has undergone banding & no evidence of bleeding in last 2 mos. |
| 7 | HIV (+)/AIDS or other severe disease that would preclude study participation. |
| 8 | Gastrointestinal disease or prior abdominal surgery, resulting in an inability to take or absorb oral medication. |
| 9 | Evidence of biliary sepsis. |
| 10 | Other primary malignancy except cervical carcinoma-in-situ or urinary bladder or non-melanoma skin cancer diagnosed within last 5 yrs. |
| 11 | Known brain metastases or patients with signs or symptoms suggestive of brain metastases unless ruled out by CT or MRI. |
| 12 | Mental incapacitation or psychiatric illness that would preclude study participation. |
| 13 | History of thrombo-embolic disease requiring full anti-coagulation within last 6 mos. |
| 14 | Uncontrolled or significant cardiovascular disease including: |
| 15 | Myocardial infarction within 12 mos; uncontrolled angina within 6 mos; Class III-IV NYHA CHF; LVEF < 45%
|
| 16 | Uncontrolled heypertension (BP > 150/100 x 24 hrs). BP must be < 150/100 at screening. Patients on calcium channel blockers that are CYP3A4 substrates should be changed to an alternative antihypertensive before study entry (sec 6.4.1).
|
| 17 | History of stroke, TIA or other ischemic event w/i last 12 mos. |
| 18 | Severe Cardiac Valve dysfunction. |
| 19 | History of bleeding disorders & thrombosis, including portal vein thrombosis coagulopathy, & ptatients on chronic anti-pletelet treatment (aspirin > 300 mg/day, clopidrogel; patients on warfarin should have frequent INR monitoring for at least the 1st month on study & may require longer monitoring to insure anticoagulation is within therapeutic range.) |
| 20 | History of allergy to BMS-582664 or related compounds & to Lidocaine or related compounds. |
| 21 | Prisoners or those who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical illness (e.g., infectious disease). |
