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A Phase I/II Study of Capecitabine (XELODA®, Roche) Plus Oxaliplatin (Eloxatin®, Sanofi) Plus ZD 1893 (IRESSA®) in the Treatment of Metastatic Colorectal Cancer

Phase 1/Phase 2
18 Years
80 Years
Not Enrolling
Colorectal Cancer

Thank you

Trial Information

A Phase I/II Study of Capecitabine (XELODA®, Roche) Plus Oxaliplatin (Eloxatin®, Sanofi) Plus ZD 1893 (IRESSA®) in the Treatment of Metastatic Colorectal Cancer



- Determine the maximum tolerated dose of capecitabine when given in combination with
oxaliplatin and gefitinib in patients with metastatic colorectal cancer. (phase I)

- Determine the response rate in patients treated with this regimen. (phase II)


- Determine the safety and toxic effects of this regimen in these patients.

- Determine the 1-year survival of patients treated with this regimen. (phase II)

- Determine the progression-free and overall survival of patients treated with this
regimen. (phase II)

OUTLINE: This is an open-label, nonrandomized, phase I, dose-escalation study of
capecitabine followed by a phase II study.

- Phase I: Patients receive oral capecitabine twice daily on days 1-14 and oxaliplatin IV
over 2 hours on day 1. Patients also receive oral gefitinib once daily beginning 5 days
before the initiation of capecitabine and oxaliplatin and continuing for the duration
of study treatment. Courses repeat every 21 days in the absence of disease progression
or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of capecitabine 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 receive oral capecitabine (at the MTD determined in phase I),
oxaliplatin IV, and oral gefitinib as in phase I.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for the phase I portion of this
study within 1-12 months; and a total of 26 patients will be accrued for the phase II
portion of this study within 8-13 months.

Inclusion Criteria


- Histologically or cytologically confirmed* colorectal cancer

- Metastatic disease

- The site of the primary tumor must have been confirmed endoscopically,
radiologically, or surgically to be the colon or rectum NOTE: *Confirmation is
not required for recurrent metastatic disease unless an interval of > 5 years
has elapsed between the initial primary surgery and the development of

- Measurable disease

- At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques
OR ≥ 10 mm by spiral CT scan

- No CNS metastases



- 18 to 80

Performance status

- ECOG 0-1

Life expectancy

- More than 3 months


- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9 g/dL (transfusion allowed)


- AST and ALT ≤ 3 times upper limit of normal (ULN)

- Bilirubin ≤ ULN

- No unstable or uncompensated hepatic disease


- Creatinine < 1.5 times ULN OR

- Creatinine clearance > 60 mL/min

- No unstable or uncompensated renal disease


- No unstable or uncompensated cardiac disease


- No evidence of clinically active interstitial lung disease

- Asymptomatic patients with chronic stable radiographic changes are eligible

- No unstable or uncompensated respiratory disease


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after study

- No known hypersensitivity to gefitinib or any of its excipients

- No known hypersensitivity to platinum compounds, fluorouracil, or capecitabine

- No severe or uncontrolled systemic disease

- Able to receive oral medication

- No known dihydropyrimidine dehydrogenase (DPD) deficiency

- No known peripheral neuropathy ≥ grade 1

- Absence of deep tendon reflexes as the sole neurological abnormality allowed

- No other significant clinical disorder or laboratory finding that would preclude
study participation

- No other malignancy within the past 5 years except basal cell skin cancer or
carcinoma in situ of the cervix (phase II only)


Biologic therapy

- Not specified


- At least 4 weeks since prior chemotherapy for metastatic colorectal cancer (phase I)

- No prior chemotherapy for metastatic disease (phase II)

- Prior fluorouracil and leucovorin calcium in the adjuvant setting allowed
provided the last treatment was administered more than 6 months before the
development of metastatic disease

- No prior irinotecan and oxaliplatin (phase II)

Endocrine therapy

- Not specified


- No concurrent radiotherapy for colorectal cancer


- See Disease Characteristics

- More than 4 weeks since prior major surgery (e.g., laparotomy)


- Recovered from all prior therapy (no unresolved chronic toxicity > grade 2)

- More than 4 weeks since prior investigational drugs

- No prior epidermal growth factor receptor inhibitor therapy (phase II)

- No concurrent phenytoin, carbamazepine, rifampin, barbiturates, or Hypericum
perforatum (St. John's wort)

- No other concurrent investigational drugs

- No other concurrent systemic therapy for colorectal cancer

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Safety Issue:


Principal Investigator

Marwan Fakih, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute


United States: Food and Drug Administration

Study ID:

I 17403



Start Date:

January 2004

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • recurrent colon cancer
  • stage IV colon cancer
  • recurrent rectal cancer
  • stage IV rectal cancer
  • Colorectal Neoplasms



Roswell Park Cancer Institute Buffalo, New York  14263