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

Alternate Title

Adjuvant Chemotherapy With or Without Monoclonal Antibody in Patients With Resected Stage III Colon Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 18 and over Pharmaceutical / Industry GW-157-001 NCI-V96-0836

Objectives

I.  Compare the overall survival of patients with surgically resected stage 
III adenocarcinoma of the colon treated with adjuvant monoclonal antibody 
17-1A (MOAB 17-1A) in combination with fluorouracil (5-FU)-based chemotherapy 
vs. 5-FU-based chemotherapy alone.

II.  Compare the disease-free interval, disease-free survival, and time to 
cancer-related death associated with these two treatments.

III.  Compare the safety profile, quality of life, and medical resource 
utilization associated with these two treatments.

IV.  Evaluate the pharmacokinetics of MOAB 17-1A given in combination with 
5-FU-based chemotherapy in a subset of patients.

V.  Evaluate human anti-mouse antibody (HAMA) response following treatment 
with MOAB 17-1A in the presence of 5-FU-based chemotherapy, and evaluate the 
effect of HAMA on MOAB 17-1A pharmacokinetics in a subset of patients.

Entry Criteria

Disease Characteristics:

Histopathologically documented stage III (Dukes' C) adenocarcinoma of the
colon

  Synchronous multiple primaries classified according to most advanced lesion

Potentially curative resection with tumor-free margins (including lateral
margins) required
  No laparoscopic resection
  Locally advanced (T4) lesions surgically excised with "intent to cure"
     No T4 lesions excised with debulking approach

Postoperative twice-normal CEA requires close evaluation for metastatic
disease

None of the following:
  Metachronous lesions
  Undifferentiated carcinoma of the colon
  Recurrent disease
  Locally advanced disease
  Carcinoma of the rectum (i.e., inferior edge of tumor lying less than 15 cm
     from the anal verge or extending below either the peritoneal reflection
     or the sacral promontory)
  Polyposis coli, Crohn's disease, or ulcerative colitis

Prior/Concurrent Therapy:

Biologic therapy:
  No prior murine or chimeric antibody or antibody fragments
  No other prior immunotherapy for any condition except autoimmune disease
     At least 3 months since cyclosporine, anti-thymocyte globulin, or other
     agent

Chemotherapy:
  No prior chemotherapy for any condition

Endocrine therapy:
  At least 3 months since corticosteroids at greater than physiologic
  replacement doses (e.g., prednisone at greater than 10 mg/day)

Radiotherapy:
  No prior radiotherapy for any condition

Surgery:
  Prior complete resection required

Patient Characteristics:

Age:
  18 and over

Performance status:
  WHO 0-2

Life expectancy:
  At least 12 months

Hematopoietic:
  WBC at least 4,000
  Platelets at least 100,000
  Hemoglobin greater than 10 g/dL

Hepatic:
  Bilirubin no more than 1.25 times greater than normal

Renal:
  Creatinine no more than 1.25 times greater than normal

Other:
  No known hypersensitivity to murine protein
  No uncontrolled infection
  No known HIV antibody
  No history of second malignancy except:
     Effectively treated nonmelanomatous skin cancer
     Carcinoma in situ of the cervix cured by surgery or other local treatment
     Other malignancy curatively treated and disease-free for at least 5 years
        (requires approval of sponsor medical advisor)
  No severe nonmalignant disease that precludes chemotherapy or prolonged
     follow-up or would complicate interpretation of safety assessments
  No psychologic, sociologic, or familial problem or geographic location
     that precludes protocol compliance
  No psychiatric or addictive disorder that precludes informed consent
  No pregnant or nursing women
     Negative pregnancy test required of fertile women
  Adequate contraception required of fertile patients

Expected Enrollment

1,800 patients will be entered over approximately 18 months.

Outline

Randomized study.  Each participating center prospectively determines whether, 
within each arm, drug modulation will be achieved with levamisole (Alternative 
A) or leucovorin calcium (Alternative B).  The following acronyms are used:
  CF          Leucovorin calcium, NSC-3590
  5-FU        Fluorouracil, NSC-19893
  LEV         Levamisole, NSC-177023
  MOAB 17-1A  Monoclonal Antibody 17-1A (Panorex), NSC-377963

Arm I:

Alternative A:  Biological Response Modifier Therapy plus Single-Agent 
Chemotherapy with Drug Modulation.  MOAB 17-1A; plus 5-FU; with LEV.

Alternative B:  Biological Response Modifier Therapy plus Single-Agent 
Chemotherapy with Drug Modulation.  MOAB 17-1A; plus 5-FU; with CF.

Arm II:

Alternative A:  Single-Agent Chemotherapy with Drug Modulation.  5-FU; with 
LEV.

Alternative B:  Single-Agent Chemotherapy with Drug Modulation.  5-FU; with CF.

Trial Contact Information

Trial Lead Organizations

GlaxoSmithkline

Richard Pazdur, MD, Protocol chair		Ph: 301-594-2473