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Gefitinib and Combination Chemotherapy in Treating Patients With Advanced or Recurrent Colorectal Cancer

This study has been terminated.
(Administratively complete.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00052585
First received: January 24, 2003
Last updated: January 15, 2013
Last verified: January 2013
History of Changes
  Purpose

Phase II trial to study the effectiveness of combining gefitinib with fluorouracil, leucovorin, and irinotecan in treating patients who have advanced or recurrent colorectal cancer. Biological therapies such as gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib with fluorouracil, leucovorin, and irinotecan may kill more tumor cells


Condition Intervention Phase
Adenocarcinoma of the Colon
Adenocarcinoma of the Rectum
Mucinous Adenocarcinoma of the Colon
Mucinous Adenocarcinoma of the Rectum
Recurrent Colon Cancer
Recurrent Rectal Cancer
Signet Ring Adenocarcinoma of the Colon
Signet Ring Adenocarcinoma of the Rectum
Stage IV Colon Cancer
Stage IV Rectal Cancer
 Drug: irinotecan hydrochloride
Drug: gefitinib
Drug: leucovorin calcium
Drug: fluorouracil
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial Of IRESSA (NSC 715055, IND 61187) In Combination With 5-FU/LV/ CPT-11 In Patients With Advanced Or Recurrent Colorectal Cancer

Resource links provided by NLM:

U.S. FDA Resources

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

Primary Outcome Measures:
  • Grade 3 or 4 toxicity, graded using the NCI CTC version 2.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
  • Response rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    95% confidence interval will be determined.


Enrollment: 50
Study Start Date: October 2002
Primary Completion Date: November 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (irinotecan, gefitinib, leucovorin, fluorouracil)
Patients receive oral gefitinib daily beginning on day 1, irinotecan IV over 90 minutes on days 1 and 15, and leucovorin calcium IV over 2 hours and fluorouracil IV over 3-5 seconds followed by a 22-hour infusion on days 1, 2, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
 Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Drug: gefitinib
Given orally
Other Names:
  • Iressa
  • ZD 1839
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU

Detailed Description:

OBJECTIVES:

I. Determine the safety of gefitinib, fluorouracil, leucovorin calcium, and irinotecan in patients with advanced or recurrent colorectal cancer.

II. Determine the major side effects of this regimen in these patients. III. Determine the response rate, progression-free survival, and overall survival of patients treated with this regimen.

IV. Correlate response and other measures of outcome with epidermal growth factor receptor expression and the expression of genes that impact upon pathways of fluoropyrimidine cytotoxicity in patients treated with this regimen.

OUTLINE: This is a non-randomized, open-label, multi-center study.

Patients receive oral gefitinib daily beginning on day 1, irinotecan IV over 90 minutes on days 1 and 15, and leucovorin calcium IV over 2 hours and fluorouracil IV over 3-5 seconds followed by a 22-hour infusion on days 1, 2, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed advanced (stage IV) or recurrent adenocarcinoma of the colon or rectum
  • Must have available tissue for immunohistochemical analysis

  • At least one unidimensionally measurable lesion

    • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
    • Tumor marker (carcinoembryonic antigen) elevation alone is insufficient for study entry
  • No known brain metastases
  • Performance status - ECOG 0-2
  • Granulocyte count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • AST less than 2 times ULN (5 times ULN if liver involvement of tumor)
  • Creatinine no greater than 1.5 times ULN
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • HIV negative
  • No other severe or uncontrolled concurrent illness that would adversely impact the safety or efficacy of study therapy
  • No ongoing or active infection
  • No other prior malignancy unless curatively treated and no evidence of recurrence
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to gefitinib
  • No psychiatric illness or social situation that would preclude study compliance
  • No prior chemotherapy for advanced disease
  • More than 4 weeks since other prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • More than 4 weeks since prior radiotherapy and recovered
  • At least 6 months since prior adjuvant therapy
  • No prior epidermal growth factor receptor inhibitor
  • No other concurrent investigational agents
  • No other concurrent anticancer therapy
  • No concurrent phenytoin, carbamazepine, barbiturates, rifampin, rifapentine, oxacarbazepine, modafinil, griseofulvin, or Hypericum perforatum
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00052585

Locations
United States, Pennsylvania
Abramson Cancer Center of The University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Peter O'Dwyer Abramson Cancer Center of the University of Pennsylvania
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00052585     History of Changes
Other Study ID Numbers: NCI-2012-02505, UPCC #06202, CDR0000258548
Study First Received: January 24, 2003
Last Updated: January 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cystadenocarcinoma
Adenocarcinoma
Adenocarcinoma, Mucinous
Colonic Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
 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

ClinicalTrials.gov processed this record on May 23, 2013