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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00025142
First Posted: January 27, 2003
Last Update Posted: May 15, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)
  Purpose

RATIONALE: Biological therapies such as gefitinib 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 more than one drug with gefitinib may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of gefitinib and oxaliplatin combined with leucovorin and fluorouracil in treating patients who have advanced solid tumors or colorectal cancer.


Condition Intervention Phase
Colorectal Cancer Drug: FOLFOX regimen Drug: fluorouracil Drug: gefitinib Drug: leucovorin calcium Drug: oxaliplatin Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Study of ZD1839 (Iressa) in Combination With Oxaliplatin, 5-Fluorouracil (5-FU) and Leucovorin (LV) in Advanced Solid Malignancies (Phase I) and Advanced Colorectal Cancers (Phase II)

Resource links provided by NLM:


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

Study Start Date: July 2001
Study Completion Date: November 2006
Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose of gefitinib and oxaliplatin when combined with fluorouracil and leucovorin calcium in patients with advanced solid tumors. (Phase I) (Phase I closed as of 5/30/02)
  • Determine the pharmacokinetics and pharmacodynamics of this regimen in these patients.
  • Determine the dose-limiting toxic effects and other toxic effects of this regimen in these patients.
  • Determine the antitumor response in patients with advanced colorectal adenocarcinoma treated with this regimen. (Phase II)
  • Determine the overall survival and time to progression in patients with advanced colorectal adenocarcinoma treated with this regimen. (Phase II)
  • Determine the presence of polymorphisms or other genetic alterations in genes implicated in the action of this regimen and determine their possible relationship with toxic effects of and antitumor response to this regimen in these patients.

OUTLINE: This is a dose-escalation study of gefitinib and oxaliplatin (L-OHP).

  • Phase I (closed as of 5/30/02): Patients receive L-OHP IV over 2 hours on day 1 and leucovorin calcium (CF) IV over 2 hours followed by fluorouracil (5-FU) IV bolus and 5-FU IV over 22 hours on days 1 and 2 during all courses. Beginning with course 2, patients also receive oral gefitinib daily on days 1-14. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) receive 2 additional courses past CR.

Sequential dose escalation of gefitinib is followed by sequential dose escalation of L-OHP. Cohorts of 3-6 patients receive escalating doses of gefitinib and L-OHP until the maximum tolerated dose (MTD) of the combination is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

  • Phase II: Patients are stratified according to prior therapy:

    • Stratum A: Received no prior therapy or received adjuvant 5-FU/CF or adjuvant 5-FU/CF/irinotecan at least 6 months ago
    • Stratum B: Received prior therapy for metastatic disease or received adjuvant 5-FU/CF fewer than 6 months ago or prior irinotecan Patients receive therapy as in phase I (closed as of 5/30/02) with L-OHP and gefitinib at the recommended phase II dose.

PROJECTED ACCRUAL: Approximately 12-15 patients will be accrued for phase I of the study within 4-6 months (Phase I closed as of 5/30/02). A total of 30-81 patients (18-46 for stratum A and 12-35 for stratum B) will be accrued for phase II of the study within 18 months.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Phase I (closed as of 5/30/02):

    • Histologically confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective
  • Phase II:

    • Histologically confirmed metastatic or unresectable colorectal adenocarcinoma
  • Measurable disease or assessable but nonmeasurable disease (including ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonis, inflammatory breast disease, abdominal masses (not followed by CT scan/MRI), or cystic lesions)

    • Disease characterized only by elevated serum tumor marker allowed
  • No known brain metastases

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-2 OR
  • Karnofsky 60-100%

Life expectancy:

  • More than 3 months

Hematopoietic:

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

Hepatic:

  • Bilirubin no greater than 1.5 mg/dL
  • AST/ALT no greater than 2.5 times upper limit of normal

Renal:

  • Creatinine normal OR
  • Creatinine clearance at least 60 mL/min

Cardiovascular:

  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No ongoing or active infection
  • No peripheral neuropathy
  • No prior allergic reactions to compounds of similar chemical or biologic composition to gefitinib or other study agents
  • No other concurrent uncontrolled illness
  • No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior bone marrow or stem cell support with high-dose chemotherapy
  • At least 24 hours since prior colony-stimulating growth factors

Chemotherapy:

  • See Biologic therapy
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • No more than 3 prior chemotherapy regimens

Endocrine therapy:

  • At least 2 weeks since prior hormonal therapy except megestrol for anorexia/cachexia

Radiotherapy:

  • No prior pelvic or whole abdominal radiotherapy
  • At least 4 weeks since other prior radiotherapy and recovered

Surgery:

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

Other:

  • At least 4 weeks since prior investigational therapy
  • No other concurrent investigational or commercial anticancer agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00025142


Locations
United States, California
Stanford Cancer Center at Stanford University Medical Center
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
National Cancer Institute (NCI)
Investigators
Study Chair: Branimir I. Sikic, MD Stanford University
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00025142     History of Changes
Other Study ID Numbers: SUMC-670
CDR0000068923 ( Registry Identifier: PDQ (Physician Data Query) )
NCI-4370
First Submitted: October 11, 2001
First Posted: January 27, 2003
Last Update Posted: May 15, 2013
Last Verified: February 2005

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
Oxaliplatin
Gefitinib
Fluorouracil
Levoleucovorin
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Antidotes
Protective Agents