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

Alternate Title

SCH-58500 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 to 75 Pharmaceutical / Industry SPRI-I/C95-177-01 NCI-V97-1182

Objectives

I.   Assess the safety of SCH-58500 when given as a single intratumoral dose 
to patients with p53 mutant head and neck squamous cell cacinoma.

II.  Assess the biological activity of SCH-58500, by confirming wild-type p53 
gene expression, as measured by reverse transcription and polymerase chain 
reaction (RT-PCR) in treated tumor tissue.

Entry Criteria

Disease Characteristics:

Histologically or cytologically confirmed recurrent or metastatic squamous
cell carcinoma of the head and neck for which curative treatment alternatives
do not exist

Immunohistochemical evidence for p53 gene mutation in the primary or recurrent
head and neck tumor tissue

Prior/Concurrent Therapy:

Biologic therapy:
 At least 28 days since prior biologic therapy and recovered
 At least 3 months since prior immunosuppressive therapy

Chemotherapy:
 At least 28 days since prior chemotherapy and recovered

Endocrine therapy:
 At least 3 months since prior systemic corticosteroid therapy
 Dexamethasone as an antiemetic is allowed

Radiotherapy:
 At least 4 weeks since prior radiation therapy for primary, recurrent or     
  metastatic disease

Surgery:
 At least 4 weeks since prior surgery for primary, recurrent or metastatic    
  disease

Other:
 No concurrent investigational drugs while actively on this study

Patient Characteristics:

Age:
 18 to 75

Performance status:
 Karnofsky at least 70%

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 within normal limits
 PTT within normal limits

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

Renal:
 Creatinine less than 1.5 mg/dL OR
 Creatinine clearance greater than 50 mL/min
 Calcium within normal limits

Other:
 Adequate nutritional and liquid intake
 No lymphoepithelioma
  Incurable nasopharyngeal carcinoma allowed
 No squamous cell carcinoma of the skin of head and neck at initial diagnosis
 No prior history of intracerebral metastases or meningeal carcinomatosis
 No prior malignancy
  Previously diagnosed head and neck carcinoma allowed
  At least 5 years since prior cervical carcinoma in situ
  At least 5 years since prior nonmelanoma skin cancer
 Not pregnant or nursing
 Effective contraception required of all fertile patients
 No serious bacterial, viral, fungal or parasitic infection
 No adenoviral infection as determined by ELISA
 At least 3 months since prior participation in investigational therapy study
 No concurrent medical condition which makes repeat biopsy, resection, or     
  administration of SCH-58500 hazardous

Expected Enrollment

6-18 patients will be entered in 3 study sites.

Outline

This is a nonrandomized, noncontrolled, multicentered, open label, pilot study.

Patients receive a single dose/single intratumoral injection of SCH-58500.  
The first 3 patients entered receive SCH-58500 at level 1.  If no dose 
limiting toxicity (DLT) is observed after 14 days of posttreatment monitoring, 
the next 3 patients receive SCH-58500 at next dose level.  Escalation to 
subsequent dose levels proceeds in the absence of DLT until biological 
activity is confirmed in 2 consecutive dose levels.

DLT is defined as any grade 4 toxicity or any grade 3 toxicity lasting more 
than 1 week.

Patients undergo regularly scheduled follow up visits for the duration of 
their lifetime.

Trial Contact Information

Trial Lead Organizations

Schering-Plough Research Institute

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