ZD 1839 Plus Combination Chemotherapy in Treating Patients With Locally Advanced, Locally Recurrent, or Metastatic Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00026364
First received: November 9, 2001
Last updated: March 19, 2013
Last verified: September 2002
  Purpose

Phase I trial to study the effectiveness of ZD 1839 combined with irinotecan, leucovorin, and fluorouracil in treating patients who have locally advanced, locally recurrent, or metastatic colorectal cancer. Biological therapies such as ZD 1839 may interfere with the growth of tumor cells and slow the growth of the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining ZD 1839 with combination chemotherapy may kill more tumor cells.


Condition Intervention Phase
Colorectal Cancer
Drug: fluorouracil
Drug: gefitinib
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study Of ZD1839 (Iressa) In Combination With Irinotecan, Leucovorin, And 5-Fluorouracil In Previously Untreated, Stage IV Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Enrollment: 22
Study Start Date: November 2001
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I

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 toxicity.

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.

Drug: fluorouracil Drug: gefitinib Drug: irinotecan hydrochloride Drug: leucovorin calcium

Detailed Description:

OBJECTIVES:

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 toxicity.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-1

Life expectancy:

  • More than 12 weeks

Hematopoietic:

  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

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

Renal:

  • Creatinine normal

Cardiovascular:

  • 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

Other:

  • 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 ileostomy
  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 12 months since prior immunotherapy

Chemotherapy:

  • At least 12 months since prior fluorouracil
  • No prior chemotherapy for advanced colorectal cancer
  • No prior irinotecan

Radiotherapy:

  • No prior radiotherapy to more than 15% of bone marrow
  • At least 4 weeks since prior major radiotherapy (e.g., chest or bone palliative radiotherapy)
  • No concurrent radiotherapy

Surgery:

  • 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

Other:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00026364

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Investigators
Study Chair: Charles S. Fuchs, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00026364     History of Changes
Other Study ID Numbers: NCI-2012-02425, DFCI-01142, NCI-3792, CDR0000069023
Study First Received: November 9, 2001
Last Updated: March 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Irinotecan
Gefitinib
Camptothecin
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on July 26, 2014