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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Completed 18 and over Pharmaceutical / Industry PCI-P120-9501 NCI-V96-0844

Objectives

I.  Estimate the maximum tolerated dose (MTD) of the radiosensitizer 
gadolinium texaphyrin (PCI-0120), and establish an appropriate intravenous 
dose for repetitive treatments in patients with brain metastases that require 
palliative radiotherapy.

II.  Establish a safety profile of PCI-0120 by evaluating an additional 20 
patients at the MTD.

III.  Evaluate the accumulation of PCI-0120 in metastases and the tumor 
response to treatment.

IV.  Describe the dose-limiting toxicity of repetitive injections of PCI-0120 
followed by radiotherapy in these patients.

V.  Determine the biolocalization of PCI-0120 in cancerous and normal tissue, 
and assess the change in tumor volume using the high (white) signal intensity 
produced by PCI-0120 on magnetic resonance imaging.

VI.  Determine the in vivo pharmacokinetics of PCI-0120 in patients treated at 
the MTD.

Entry Criteria

Disease Characteristics:

Brain metastases (demonstrated by radiography) that require palliative
radiotherapy

Resected brain metastases, leptomeningeal metastases, and cerebrospinal fluid
involvement allowed only on phase IB portion of study

Prior/Concurrent Therapy:

At least 4 weeks since cytotoxic chemotherapy (6 weeks since nitrosoureas)
At least 14 days since prior investigational radiosensitizers
No prior radiotherapy to planned treatment site

Patient Characteristics:

Age:
  18 and over

Performance status:
  0-2

Life expectancy:
  At least 2 months

Hematopoietic:
  WBC at least 3,000
  AGC at least 1,500
  Platelets greater than 100,000

Hepatic:
  Bilirubin less than 2 mg/dL
  AST/ALT less than twice normal
  Alkaline phosphatase less than twice normal
  PT and aPTT no more than 1.5 times normal

Renal:
  Creatinine less than 1.5 mg/dL

Neurological status:
  Neurologic function no greater than 2

Other:
  No contraindication to MRI and/or CT
  No medical or psychiatric condition that precludes informed consent
  No pregnant or nursing women
     Negative pregnancy test required of fertile patients
  Men should avoid pregnancy-inducing sexual activity while on study
  Able to comply with treatment and adequate follow-up

Expected Enrollment

Approximately 50 patients will be entered.  Duration of study is expected to 
be 6-12 months.

Outline

Radiotherapy with Radiosensitization.  External-beam whole-brain irradiation 
using at least 4 MV photons; with Gadolinium Texaphyrin, PCI-0120 (prior to 
each radiotherapy fraction).

Trial Contact Information

Trial Lead Organizations

Pharmacyclics, Incorporated

Markus Renschler, MD, Protocol chair		Ph: 408-774-3366