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

Alternate Title

EMD 121974 in Treating Patients With Locally Advanced or Metastatic Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over NCI IUMC-9909-40 NCI-T99-0076, NCT00004258, T99-0076

Objectives

I. Determine the safety and tolerability of EMD 121974 in patients with 
advanced or metastatic cancer.

II. Correlate various surrogate markers of antiangiogenic activity with EMD 
121974 therapy including magnetic resonance imaging and PET scans, serum 
assays for various angiogenic and antiangiogenic factors, serum and urine 
markers of calcium metabolism, and tumor biopsies.

Entry Criteria

Disease Characteristics:

Histologically or cytologically confirmed locally advanced or metastatic
cancer that is considered incurable and for which no standard curative therapy
exists
 No primary CNS malignancies

Measurable evidence of residual, recurrent, or metastatic disease

No prior CNS metastases with residual abnormal findings on neuroradiologic
studies
 Prior CNS metastases allowed provided at least 6 months from definitive
  therapy and a normal CT or MRI of the brain

Prior/Concurrent Therapy:

Biologic therapy:
 At least 2 weeks since prior hematopoietic growth factor or cytokine therapy
  and recovered
 No concurrent immunotherapy

Chemotherapy:
 At least 4 weeks since prior chemotherapy (at least 6 weeks since prior
  nitrosoureas or mitomycin) and recovered
 No concurrent chemotherapy

Endocrine therapy:
 No concurrent corticosteroids except for steroid replacement therapy or
  chronic low dose (no greater than 10 mg/day oral prednisone) therapy for
  nonmalignant conditions
 No concurrent hormonal therapy except oral contraceptives or hormonal
  replacement therapy

Radiotherapy:
 At least 2 weeks since prior radiotherapy and recovered
 No concurrent radiotherapy

Surgery:
 At least 2 weeks since prior surgery and recovered

Other:
 At least 4 weeks since other prior investigational drugs
 No concurrent oral or parenteral anticoagulants except anticoagulants for
  central venous catheters including low dose warfarin (1-2 mg/day) and/or
  heparin
 No concurrent oral COX-2 specific inhibitors (e.g., celecoxib or rofecoxib)

Patient Characteristics:

Age:
 18 and over

Performance status:
 ECOG 0-2

Life expectancy:
 At least 3 months

Hematopoietic:
 Absolute neutrophil count at least 1,500/mm3
 Hemoglobin at least 9 mg/dL (may be post transfusion)
 Platelet count at least 100,000/mm3

Hepatic:
 Bilirubin normal
 SGOT/SGPT no greater than 2.5 times upper limit of normal
 PT/PTT normal

Renal:
 Creatinine no greater than 1.5 mg/dL

Other:
 Not pregnant or nursing
 Negative pregnancy test
 Fertile patients must use effective contraception
 No active infection requiring parenteral antibiotics
 No documented abnormal CNS exam with seizure disorder or major
  neuropsychiatric problems

Expected Enrollment

A total of 31-40 patients will be accrued for this study.  

Outline

This is a dose-escalation study.

Patients receive EMD 121974 IV over 1 hour twice weekly for 4 weeks.  
Treatment continues for an additional course in the absence of unacceptable 
toxicity.  Patients with stable or responding disease may continue therapy 
indefinitely past the 2 courses until disease progression.

Cohorts of 3-6 patients receive escalating doses of EMD 121974 until the 
maximum tolerated dose (MTD) is determined.  The MTD is defined as the dose 
preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting 
toxicities. 

Patients are followed every 3 months for the first year, and then every 4 
months thereafter until disease progression.

Trial Contact Information

Trial Lead Organizations

Indiana University Melvin and Bren Simon Cancer Center

Michael Gordon, MD, Protocol chair(Contact information may not be current)		Ph: 480-323-1000

Registry Information
Official Title		A Phase I Trial of EMD 121974 in Patients with Advanced or Metastatic Cancer
Trial Start Date		1999-12-20
Registered in ClinicalTrials.gov		NCT00004258
Date Submitted to PDQ		2000-01-03
Information Last Verified		2007-05-23