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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)


Phase 2
18 Years
N/A
Not Enrolling
Both
Colorectal Cancer

Thank you

Trial Information

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)


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Branimir I. Sikic, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Stanford University

Authority:

United States: Federal Government

Study ID:

SUMC-670

NCT ID:

NCT00025142

Start Date:

July 2001

Completion Date:

November 2006

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

Name

Location

Stanford Cancer Center at Stanford University Medical CenterStanford, California  94305