Dose escalation of oxaliplatin, gemcitabine and capecitabine in the treatment of patients
with advanced gastrointestinal malignancies and other solid tumors.
To define the maximum tolerated dose of oxaliplatin, gemcitabine and capecitabine in the
treatment of patients with advanced gastrointestinal malignancies and other solid tumors.
1. Histological Diagnosis: Patients must have a histological or cytological proven
advanced gastrointestinal or other solid malignancy.
2. Measurable or Evaluable Disease: See RECIST Criteria: www.cancer.gov/dip/RECIST
3. Age: Patients must be 18 years old or older. Because no dosing or toxicity data are
currently available on the use of oxaliplatin in patients <18 years of age, children
are excluded from this study, but will be eligible for other pediatric Phase I
single-agent trials, when available.
4. Performance Status: NCI CTC 0-2.
5. Life Expectancy: >=8 weeks.
6. Recovery from Prior Therapy: Patients must have recovered from the acute toxic
effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering
this study and must be without significant systemic illness (e.g. infection). No
chemotherapy or radiotherapy may be given within 3 weeks prior to the start of
protocol treatment. Patients must have received <= 2 prior chemotherapy regimes.
7. Recovery from Intercurrent Illness: Patients must have recovered from uncontrolled
intercurrent illness including, but not limited to, ongoing or active infection,
symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.
8. Hematological Status: Patients must have adequate bone marrow function which is
defined as an absolute neutrophil count >= 1,500/mm³, platelet count >= 100,000/mm³
and hemoglobin >= 9 g/dl.
9. Hepatic Function: Total bilirubin must be <= institutional limit of normal (ULN).
Transaminases (SGOT and/or SGPT) must be <= 4 x ULN.
10. Neurological Status: Patients must not have active CNS metastases. Patients with
Grade 2 or higher peripheral neuropathy are ineligible due to the potential
neurological complications of oxaliplatin therapy.
11. Renal Function: Patients must have adequate renal function defined as serum
creatinine <= 2.0 mg/dl or creatinine clearance >= 60 ml/min/1.73m² for patients with
creatinine levels above 2.0 mg/dl.
12. Sexually Active Patients: For all sexually active patients, the use of adequate
barrier contraception (hormonal or barrier method of birth control) will be required
during therapy, prior to study entry and for the duration of study participation.
Non-pregnant status will be determined in all women of childbearing potential.
Pregnant and nursing women patients are not eligible.
13. HIV-Positive Patients: Patients receiving anti-retroviral therapy (HAART) for HIV
infection are excluded from the study because of possible pharmacokinetic
interactions. Appropriate protocols will be offered to patients receiving HAART
therapy, when indicated.
14. No known hypersensitivity to oxaliplatin, gemcitabine or capecitabine
15. No pre-existing clinically significant cardiac, hepatic or renal disease.
16. Informed Consent: After being informed of the treatment involved, patients must give
written consent. The patient should not have any serious medical or psychiatric
illness that would prevent either the giving of informed consent or the receipt of
17. Inclusion of Women and Minorities: Entry to this study is open to both men and women
and to all racial and ethnic groups.