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A Phase I/ Randomized Phase II Trial Of Oxaliplatin (NSC #266046) With Or Without ZD 1839 (NSC # 715055) In Patients With Advanced Colorectal Carcinoma

Phase 1/Phase 2
18 Years
Not Enrolling
Colorectal Cancer

Thank you

Trial Information

A Phase I/ Randomized Phase II Trial Of Oxaliplatin (NSC #266046) With Or Without ZD 1839 (NSC # 715055) In Patients With Advanced Colorectal Carcinoma


- Determine the recommended phase II dose of gefitinib when administered in combination
with oxaliplatin in patients with metastatic or locally recurrent colorectal cancer.

- Determine the dose-limiting toxicity of this regimen in these patients.

- Compare the time to progression, objective response rate, and median and overall
survival in patients treated with oxaliplatin with or without gefitinib.

- Compare the toxicity of these regimens in these patients.

OUTLINE: This is a phase I dose-escalation study of gefitinib followed by a phase II
randomized, multicenter study. Patients are stratified according to ECOG performance status
(0 vs 1-2).

- Phase I: Patients receive oxaliplatin IV over 2 hours on day 1 and oral gefitinib once
daily on days 1-21. Treatment repeats every 21 days in the absence of disease
progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gefitinib 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.

- Phase II: Patients are randomized to one of two treatment arms.

- Arm I: Patients receive oxaliplatin IV over 2 hours on day 1.

- Arm II: Patients receive oxaliplatin as in arm I and oral gefitinib once daily at
the MTD on days 1-21.

In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease
progression or unacceptable toxicity. Patients in arm II with stable or responding disease
after 6 courses may continue to receive gefitinib alone until disease progression.

PROJECTED ACCRUAL: Approximately 77 patients (9 for phase I and 68 for phase II) will be
accrued for this study within 12-14 months.

Inclusion Criteria


- Histologically or cytologically confirmed adenocarcinoma of the colon or rectum that
is not amenable to potentially curative surgical resection

- Metastatic or locally recurrent disease

- Tumor in liver or lung accessible to needle biopsy by ultrasound or CT scan guidance

- At least 1 measurable lesion

- At least 20 mm by conventional techniques, including physical examination, CT
scan, or MRI OR

- At least 10 mm by spiral CT scan

- Lesions on colonoscopic examination or barium studies, bone metastases, CNS
lesions, and ascites are not considered measurable

- Failed prior therapy with fluorouracil, leucovorin calcium, and irinotecan given
either sequentially or in combination

- No known brain metastases



- 18 and over

Performance status:

- ECOG 0-2

Life expectancy:

- At least 3 months


- 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 no greater than 1.5 mg/dL

- AST/ALT no greater than 2.5 times upper limit of normal


- Creatinine no greater than 1.5 mg/dL OR

- Creatinine clearance at least 60 mL/min


- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No peripheral neuropathy greater than grade 1

- No other concurrent uncontrolled illness that would preclude study

- No concurrent psychiatric illness or social situation that would preclude study

- No ongoing or active infection

- No prior allergic reaction to compounds of similar chemical or biologic composition
to oxaliplatin or gefitinib

- No other concurrent malignancy except non-melanoma skin cancer or carcinoma in situ
of the cervix unless considered to be at less than 30% risk of relapse after
completion of therapy


Biologic therapy:

- No prior epidermal growth factor inhibitor

- At least 24 hours since prior colony-stimulating factors

- No concurrent colony-stimulating factors during first course of study therapy


- See Disease Characteristics

- No more than 2 prior chemotherapy regimens for metastatic disease

- Prior adjuvant chemotherapy allowed

- At least 4 weeks since prior cytotoxic chemotherapy and recovered

- No prior cisplatin or oxaliplatin

Endocrine therapy:

- Not specified


- At least 4 weeks since prior radiotherapy and recovered


- See Disease Characteristics

- At least 4 weeks since prior surgery


- At least 30 days since prior investigational agents

- Recovered from prior therapy

- No concurrent anti-retroviral therapy for HIV

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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Recommended dose of ZD1839 in combination with oxaliplatin

Outcome Time Frame:

3 weeks

Safety Issue:


Principal Investigator

Hedy L. Kindler, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Chicago


United States: Federal Government

Study ID:




Start Date:

September 2001

Completion Date:

February 2005

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



University of Chicago Cancer Research Center Chicago, Illinois  60637
Loyola University Medical Center Maywood, Illinois  60153
Ingalls Memorial Hospital Harvey, Illinois  60426
Memorial Hospital of South Bend South Bend, Indiana  46601
Evanston Northwestern Health Care Evanston, Illinois  60201
Louis A. Weiss Memorial Hospital Chicago, Illinois  60640
Oncology/Hematology Associates of Central Illinois, P.C. Peoria, Illinois  61602
Central Illinois Hematology Oncology Center Springfield, Illinois  62701
Fort Wayne Medical Oncology and Hematology, Inc. Fort Wayne, Indiana  46885-5099
Decatur Memorial Hospital Cancer Care Institute Decatur, Illinois  62526
Oncology Care Associates, P.L.L.C. Saint Joseph, Michigan  49085
LaGrange Memorial Hospital LaGrange, Illinois  60525