Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information

Alternate Title

Ralitrexed in Treating Patients with Metastatic Colorectal Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 18 and over NCI E-6293 E6293

Objectives

I.  Assess the objective response rate in patients with advanced, unresectable 
colorectal cancer treated with ICI D1694 (Tomudex) as either first-line 
treatment or following treatment with a fluorouracil-based regimen with or 
without leucovorin.

II.  Evaluate the toxicity associated with this treatment.

III.  Assess the prognostic value of thymidylate synthase expression with 
respect to tumor response, as measured by immunohistochemistry.

Entry Criteria

Disease Characteristics:

Histologically confirmed colorectal cancer that is metastatic and beyond
possible curative surgery
  Tumor slides/blocks and normal tissue blocks required within 1 month of
  registration

In one of the following treatment categories:
  No prior chemotherapy for metastatic disease
  Prior chemotherapy for metastatic disease with only one regimen that did not
     include leucovorin
  One prior regimen for metastatic disease that included leucovorin

Bidimensionally measurable disease
  At least 1 previously unirradiated lesion that is at least 2 x 2 cm on CT,
  ultrasound, or chest x-ray

No clinically significant ascites or pleural effusion

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  See Disease Characteristics
  Prior adjuvant chemotherapy with any regimen completed more than 1 year
     prior to entry allowed
  No more than one prior chemotherapy regimen for metastatic disease
  At least 4 weeks since chemotherapy for metastatic disease

Endocrine therapy:
  Not specified

Radiotherapy:
  At least 2 weeks since radiotherapy and recovered

Surgery:
  At least 3 weeks since major surgery and recovered

Patient Characteristics:

Age:
  18 and over

Performance status:
  ECOG 0 or 1

Hematopoietic:
  ANC at least 2,000
  Platelets at least 100,000

Hepatic:
  Bilirubin no greater than 1.5 mg/dL
  AST or ALT no greater than 2.5 times normal
  Alkaline phosphatase no greater than 3 times normal (5 times normal if due
     to metastases)

Renal:
  Creatinine normal

Metabolic:
  No uncontrolled metabolic disease, e.g., diabetes mellitus or hypothyroidism

Cardiovascular:
  No uncontrolled cardiac condition

Other:
  No significant, active infection (e.g., pneumonia, peritonitis, or wound
     abscess)
  No dementia, altered mental status, or psychiatric risk that precludes
     informed consent or study compliance
  No other serious intercurrent illness
  No second malignancy within 5 years except curatively treated:
     In situ cervical carcinoma
     Nonmelanomatous skin cancer
  No pregnant or nursing women
  Effective contraception advised of fertile patients

Blood/body fluid analyses and imaging/exams for tumor measurement within 14
  days prior to registration
Other scans/imaging studies within 42 days prior to registration

Expected Enrollment

Up to 144 patients will be entered over approximately 18 months.  If fewer 
than 4 of the first 22 previously untreated patients or fewer than 2 of the 
first 26 previously treated patients/stratum respond, accrual to that stratum 
will cease.

Outline

Single-Agent Chemotherapy.  ICI D1694, Tomudex, TDX, NSC-639186.

Zalcberg JR, Ibrahim J, Johnston PG, et al.: ECOG phase II study of tomudex in advanced colorectal cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 16: A951, 268a, 1997.

Extermann M, Bonetti M, Sledge GW, et al.: MAX2--a convenient index to estimate the average per patient risk for chemotherapy toxicity; validation in ECOG trials. Eur J Cancer 40 (8): 1193-8, 2004.[PUBMED Abstract]

Cunningham D, Zalcberg J, Maroun J, et al.: Efficacy, tolerability and management of raltitrexed (Tomudex) monotherapy in patients with advanced colorectal cancer. A review of phase II/III trials. Eur J Cancer 38 (4): 478-86, 2002.[PUBMED Abstract]

Extermann M, Bonetti M, Sledge GW, et al.: MAX2: A convenient index to estimate the average per patient risk of severe toxicity from a chemotherapy regimen. Testing in ECOG studies. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1459, 2002.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Al Benson, MD, FACP, Protocol chair		Ph: 312-695-6180