A Phase I Dose Escalation Study to Assess the Maximum Tolerated Dose and Feasibility of Combining Oral Capecitabine (Xeloda) and Conformal Radiotherapy (CRT) for Patients With Unresectable Hepatocellular Carcinoma, Multiple Hepatic Metastases or Cholangiocarcinoma
- Provide written informed consent prior to study-specific screening procedures, with
the understanding that the patient has the right to withdraw from the study at any
time, without prejudice.
- Age >18 years
- Ambulatory outpatients (if applicable), with Karnofsky performance status of >60
- Histologically or cytologically confirmed unresectable hepatocellular carcinoma,
liver mets with no evidence of extrahepatic disease, or cholangiocarcinoma. (see
exclusion criteria 10)
- At least one measurable lesion according to the RECIST criteria which has not been
irradiated (i.e. newly arising lesions in previously irradiated areas are accepted).
Ascites, pleural effusion, and bone metastases are not considered measurable.
Minimum indicator lesion size: > 10 mm measured by spiral CT or >20mm measured by
- Protocol Specific Laboratory Values as described below in section 6.9 number15.
- Has a negative serum pregnancy test within 7 days prior to start of therapy (female
patients of childbearing potential).
- Have concomitant medications been reviewed with patient to address contraindicated
medications described in protocol section 6.2.8 and have precautions been taken as
recommended for each drug? Includes Allopurinol, Cimetidine, Sorivudine and
Brivudine, Anticoagulants, Phenytoin, and Laxatives.
- Pregnant or lactating woman. Woman of childbearing potential with either a positive
or no pregnancy test at baseline. Woman or men of childbearing potential not using a
reliable and appropriate contraceptive method. (Postmenopausal woman must have been
amenorrheic for at least 12 months to be considered of non-childbearing potential).
Patients will agree to continue contraception for 30 days from the date of the last
study drug administration
- Life expectancy < 3 months.
- Serious, uncontrolled, concurrent infection(s).
- Any prior fluoropyrimidine therapy (unless given in an adjuvant setting and completed
at least 12 months earlier).
- Prior unanticipated severe reaction to fluoropyrimidine therapy, known sensitivity to
5-fluorouracil or known DPD deficiency.
- Completion of previous chemotherapy regimen < four weeks prior to the start of study
treatment, or with related toxicities unresolved prior to the start of study
- Treatment for other carcinomas within the last five years, except cured non-melanoma
skin and treated in-situ cervical cancer.
- Participation in any investigational drug study within 4 weeks preceding the start of
- Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic
coronary artery disease and cardiac arrhythmias not well controlled with medication)
or myocardial infarction within the last 12 months.
- Evidence of extrahepatic disease or history of uncontrolled seizures, central nervous
system disorders or psychiatric disability judged by the investigator to be
clinically significant, precluding informed consent, or interfering with compliance
of oral drug intake
- Other serious uncontrolled medical conditions that the investigator feels might
compromise study participation.
- Major surgery within 4 weeks of the start of study treatment, without complete
- Lack of physical integrity of the upper gastrointestinal tract or malabsorption
- Known, existing uncontrolled coagulopathy
- Any of the following laboratory values:
- Abnormal hematologic values (neutrophils < 1.5 x 109/L, platelet count < 100 x
- Impaired renal function (estimated creatinine clearance <50ml/min as calculated
with Cockroft-Gault equation.
- Serum bilirubin > 2.0 x upper normal limit.
- AST, ALT (SGOT/SGPT) > 2.5 x upper normal limit (or > 5 x upper normal limit in
the case of liver metastases).
- Alkaline phosphatase > 2.5 x upper normal limit (or > 5 x upper normal limit in
the case of liver metastases).
- Unwillingness to give written informed consent or provide HIPAA privacy
- Unwillingness to participate or inability to comply with the protocol for the
duration of the study.
- Patient taking a contraindicated medication(s) described in section 6.2.8 (see
inclusion criteria #8 for list of agents) and no appropriate substitute agent is
available, or patient unable or refuses to take substitute agent.