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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over MSKCC-93019 NCI-V93-0246

Objectives

I.  Estimate the objective response rate (CR and PR) of patients with advanced 
gastric and pancreatic cancer treated with the thymidylate synthase inhibitor 
ICI D1694.

II.  Characterize further the toxicities of ICI D1694 in these patients.

Entry Criteria

Disease Characteristics:

Microscopically confirmed pancreatic or gastric cancer not
amenable to surgery, radiotherapy, or other potentially
curative therapy
  Adenocarcinoma of the gastroesophageal junction eligible

Bidimensionally measurable disease (WHO criteria) required as
follows:
  Palpable lesion with 1 dimension at least 2.5 cm or lesion
  measurable by ultrasound or CT scan with both dimensions at
  least 1.0 cm including:
     Skin nodule
     Clinically involved superficial lymph nodes
     Nodular lung metastases surrounded by aerated lung
     Deeply located lesions visible on ultrasound, CT scan, or
        MRI

  Lesion in previously irradiated field must show evidence of
  disease progression or be 3 months past treatment to be
  considered measurable

The following are not considered measurable or evaluable (but
are included in overall assessment):
  Lymphedema
  Ascites
  Meningeal disease
  Bone marrow infiltration
  Osteoblastic bone lesions

No intracerebral metastases

Prior/Concurrent Therapy:

No concomitant systemic anticancer therapy
No unresolved systemic toxicity from prior anticancer therapy

Biologic therapy:
  Not specified

Chemotherapy:
  For pancreatic cancer:
     No prior chemotherapy for advanced disease
     Prior chemotherapy used in conjunction with radiotherapy
        for locally advanced disease allowed
     At least 4 weeks since chemotherapy

  For gastric cancer:
     No more than 1 prior systemic therapy for advanced disease
     At least 4 weeks since chemotherapy (8 weeks since
        nitrosoureas or mitomycin)

Endocrine therapy:
  Concomitant steroid therapy allowed as anti-emetic or for
  replacement therapy only

Radiotherapy:
  No irradiation to more than 30% of bone marrow (i.e., to the
  whole pelvis or more than half of the spine)

Surgery:
  Not specified

Other:
  No concomitant administration of any folate-containing
  vitamin

Patient Characteristics:

Age:
  18 and over

Performance status:
  ECOG 0-2

Life expectancy:
  At least 12 weeks

Hematopoietic:
  (within 1 week prior to entry)
  WBC more than 4,000
  Platelets more than 100,000
  Hb at least 10 g/dl

Hepatic:
  (within 1 week prior to entry)
  Bilirubin no greater than 1.25 x ULN
  SGOT/SGPT no greater than 2 x ULN (5 x ULN if elevation is
     related to hepatic metastases)

Renal:
  (within 1 week prior to entry)
  Creatinine no greater than 1.25 x ULN

Other:
  No serious active or uncontrolled infection
  No serious active or uncontrolled medical condition
  No second cancer except:
     Adequately treated in situ cervical carcinoma
     Nonmelanomatous carcinoma of the skin
  No pregnant or nursing women

Expected Enrollment

Up to 40 patients for each disease category (pancreatic and gastric) will be 
accrued to this multicenter study.  If no response is observed in the first 20 
patients accrued in a category, the study will be terminated for that disease; 
if 4 or more responses are seen during recruitment of the final 20 patients 
within a category, accrual will cease and further development of ICI D1694 
will be considered.

Outline

Nonrandomized study.

Single-Agent Chemotherapy.  ICI D1694.

Pazdur R, Casper ES, Meropol NJ, et al.: Phase II trial of tomudex (ZD1694): a thymidylate synthase inhibitor, in advanced pancreatic cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-613, 207, 1994.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Ephraim Casper, MD, Protocol chair		Ph: 908-542-3000 Email: caspere@mskcc.org