Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Alternate Title

Gene Therapy With SCH-58500 in Treating Patients With Primary or Metastatic Malignant Tumors of the Liver That Express the p53 Gene

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 to 74 Pharmaceutical / Industry SPRI-C95-063-01 NCI-V97-1179

Objectives

I.  Assess the safety of SCH-58500 when given as a single hepatic artery bolus 
infusion.

II.  Assess the biological activity of SCH-58500 against hepatocellular 
cancers and liver metastases of colorectal cancer when given as a single 
hepatic artery bolus infusion.

III.  Assess the effect of dose of SCH-58500 given as a single hepatic artery 
bolus infusion on safety and efficacy in these patients.

IV.  Describe the pharmacokinetics of SCH-58500.

Entry Criteria

Disease Characteristics:

Histologically confirmed hepatocellular carcinoma that is unresectable or 
colorectal carcinoma with incurable liver metastases

Must have evidence of p53 gene alteration in primary or metastatic tumor tissue

Presence of antiadenovirus type 5 antibodies at screening

Prior/Concurrent Therapy:

At least 3 months since any other investigational therapy

Biologic therapy:
 No prior local or regional biological therapy against liver tumor

Chemotherapy:
 At least 4 weeks since prior chemotherapy
 No prior local or regional chemotherapy against liver tumor

Endocrine therapy:
 At least 3 months since systemic corticosteroid therapy

Radiotherapy:
 No prior local or regional radiotherapy against liver tumor

Surgery:
 Not specified

Other:
 At least 3 months since other immunosuppressive therapy

Patient Characteristics:

Age:
 18-74

Performance status:
 Karnofsky 70-100%

Life expectancy:
 At least 3 months

Hematopoietic:
 WBC at least 3,000/mm3
 ANC at least 1,000/mm3
 Platelet count at least 100,000/mm3
 PT and PTT within normal range
 Hematocrit at least 25% (may be transfused prior to enrollment)

Hepatic:
 Bilirubin less than 1.5 mg/dL
 AST and ALT less than 2 times upper limit of normal

Renal:
 Creatinine less than 1.8 mg/dL OR
 Creatinine clearance greater than 50 mL/min

Pulmonary:

 Oxygen saturation at least 90% on room air

Other:
 HIV negative
 No adenoviral infection
 No uncontrolled serious bacterial, viral, fungal, or parasitic infection
 Not pregnant or nursing
 Adequate contraception required of all fertile patients during and 6 months
  after SCH-58500 treatment

Expected Enrollment

There will be an accrual of 21-42 patients in approximately 7-14 months.

Outline

This is an open label, nonrandomized, single dose, dose escalation study.

The first 3 patients receive SCH-58500 by hepatic artery infusion at dose 
level 1 at least 15 minutes after completion of angiography.  If no dose 
limiting toxicity (DLT) is observed, then the next 3 patients receive dose 
level 2.  Dose escalation proceeds in subsequent cohorts in the absence of 
DLT. 

If three of the initial patients treated with SCH-58500 at dose level 1 
experience DLT, the next three patients are entered at dose level 0.  If dose 
level 0 exceeds the maximum tolerated dose, the study is terminated.  The MTD 
is defined as the dose immediately below that at which 3 patients experience 
DLT.

Patients may elect for surgical implantation of a hepatic artery infusion pump 
and subsequent regional cytotoxic chemotherapy via hepatic artery infusion.  
These patients have exploratory laparotomy with pump placement between days 
3-7.  Other patients undergo either fine needle aspiration or core biopsy of 
the liver tumor and normal liver.

Posttreatment observation lasts for at least 72 hours after achieving adequate 
hemostasis.  

Trial Contact Information

Trial Lead Organizations

Schering-Plough Research Institute

Jo Ann Horowitz, MD, Protocol chair		Ph: 908-298-4000; 888-223-4272