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A Phase I Study Of ZD1839 (Iressa) In Combination With Irinotecan, Leucovorin, And 5-Fluorouracil In Previously Untreated, Stage IV Colorectal Cancer

Phase 1
18 Years
Not Enrolling
Colorectal Cancer

Thank you

Trial Information

A Phase I Study Of ZD1839 (Iressa) In Combination With Irinotecan, Leucovorin, And 5-Fluorouracil In Previously Untreated, Stage IV Colorectal Cancer


I. Determine the maximum tolerated dose of ZD 1839 in combination with irinotecan,
leucovorin calcium, and fluorouracil in patients with locally advanced, locally recurrent,
or metastatic colorectal cancer.

II. Determine the dose-limiting toxicity of this regimen in these patients. III. Determine
the pharmacokinetics of this regimen in these patients. IV. Determine the objective response
rate in patients treated with this regimen.

V. Correlate epidermal growth factor receptor expression with the probability of objective
tumor response in these patients.

OUTLINE: This is a multicenter, dose-escalation study of ZD 1839.

Patients receive oral ZD 1839 daily. Beginning on day 15, patients receive irinotecan IV
over 90 minutes, leucovorin calcium IV over 15 minutes, and fluorouracil IV weekly on weeks
1-2. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable

Cohorts of 3-6 patients receive escalating doses of ZD 1839 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 toxicity. Once the MTD is determined, 10 additional
patients are accrued to receive treatment at the MTD.

Patients are followed for 30 days.

Inclusion Criteria


- Histologically or cytologically confirmed adenocarcinoma of the colon or rectum

- Locally advanced, locally recurrent, or metastatic disease

- Not curable by surgery and/or not amenable to radiotherapy with curative intent

- Histological or cytological confirmation of metastatic cancer not required for
patients with prior surgically resected colorectal cancer if more than 5 years
elapsed between primary surgery and development of metastatic disease OR if
primary cancer was stage I or II

- Prior adjuvant therapy with fluorouracil or immunotherapy for resected stage II, III,
or IV disease allowed

- Measurable disease

- No known brain metastases



- 18 and over

Performance status:

- ECOG 0-1

Life expectancy:

- More than 12 weeks


- WBC at least 3,000/mm^3

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3


- Bilirubin normal

- AST/ALT no greater than 5 times upper limit of normal


- Creatinine normal


- No uncontrolled high blood pressure

- No unstable angina

- No symptomatic congestive heart failure

- No myocardial infarction within the past 6 months

- No serious uncontrolled cardiac arrhythmia

- No New York Heart Association class III or IV heart disease


- No active or uncontrolled infection

- No predisposing colonic or small bowel disorders with uncontrolled symptoms as
indicated by more than 3 loose stools daily in patients without a colostomy or

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or adequately treated noninvasive carcinomas

- No other concurrent medical or psychiatric condition that would preclude study

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception


Biologic therapy:

- At least 12 months since prior immunotherapy


- At least 12 months since prior fluorouracil

- No prior chemotherapy for advanced colorectal cancer

- No prior irinotecan


- No prior radiotherapy to more than 15% of bone marrow

- At least 4 weeks since prior major radiotherapy (e.g., chest or bone palliative

- No concurrent radiotherapy


- At least 4 weeks since prior major surgery (e.g., laparotomy) and recovered

- At least 2 weeks since prior minor surgery and recovered

- No concurrent ophthalmic surgery


- No prior ZD 1839

- No other concurrent investigational or commercial agents or therapies for malignancy

- No concurrent combination antiretroviral therapy for HIV

- No concurrent oral retinoids

- No concurrent prochlorperazine on day of irinotecan administration

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Charles S. Fuchs, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Dana-Farber Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

November 2001

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • stage IV colon cancer
  • stage IV rectal cancer
  • recurrent colon cancer
  • recurrent rectal cancer
  • adenocarcinoma of the colon
  • adenocarcinoma of the rectum
  • Colorectal Neoplasms



Massachusetts General Hospital Cancer Center Boston, Massachusetts  02114
Dana-Farber Cancer Institute Boston, Massachusetts  02115