A Phase I/II STudy of Oxaliplatin, Oral Capecitabine and Sorafenib in Patients With Advanced Pancreatic and Biliary Carcinoma"
- Patients must have histologically or cytologically confirmed locally advanced
inoperable or metastatic adenocarcinoma of the pancreas or biliary tract who have not
previously received more than one systemic treatment for their disease.
- Age at least 18 years old
- ECOG performance status 0-2.
- Patients must have adequate organ and marrow function as defined below:
- WBC at least 3,000
- ANC at least 1,500
- PLT at least 100,000
- total bilirubin must be less than 2.5 x institutional upper limit of norm
- AST(SGOT)/ALT(SGPT) must be less than 5 X institutional upper limit of normal
- creatinine clearance must be greater than 50 mL/min as calculated by the
- Patients with ≤ grade 2 (CTC 3.0) neuropathy.
- At least one measurable lesion as defined by RECIST criteria
- The effects of oxaliplatin, capecitabine and sorafenib on the developing human fetus
at the recommended therapeutic dose are unknown. For this reason and because DNA
alkylating agents are known to be teratogenic, women of child-bearing potential and
men must agree to use adequate contraception (hormonal or barrier method of birth
control) prior to study entry and for the duration of study participation. Should a
woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her treating physician immediately.
- Because the risk of toxicity in nursing infants secondary to oxaliplatin treatment of
the mother is unknown but may be harmful, breastfeeding should be discontinued if the
mother is treated with oxaliplatin.
- Ability to understand and the willingness to sign a written informed consent
- No concomitant radiation therapy, or other systemic cancer therapies.
- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other toxicities.
- History of allergy to platinum compounds, capecitabine, sorafenib or to antiemetics
appropriate for administration in conjunction with protocol-directed chemotherapy.
- Uncontrolled intercurrent illness including, but not limited to: ongoing or active
infection, thrombolic or embolic events such as cerebrovascular accident including
transient ischemic attacks within the past 6 months, symptomatic congestive heart
failure, unstable angina pectoris within 3 months prior to entry study, myocardial
infarction within 6 months prior to study entry, ongoing cardiac arrhythmia
(excluding atrial fibrillation), uncontrolled hypertension (systolic blood pressure >
150 mmHg or diastolic blood pressure > 90 mmHg, despite optimal medical management),
pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of
study drug, or any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of
first dose of study drug, serious non-healing wound, ulcer, or bone fracture,
evidence or history of bleeding diathesis or coagulopathy.
- Pregnant or nursing women are excluded from this study because oxaliplatin,
capecitabine and sorafenib is a DNA alkylating agent with the potential for
teratogenic or abortifacient effects. Female patients of reproductive potential must
have a negative urine or serum pregnancy test within two weeks prior to enrolling.
- Major surgery, open biopsy or significant traumatic injury within 4 weeks of first
- Because of drug interactions with sorafenib, use of St. John's Wort or rifampin
(rifampicin) is contraindicated. Patients may discontinue the use of these drugs to
become eligible for the study
- Any condition that impairs patient's ability to swallow whole pills.
- HIV-positive patients receiving anti-retroviral therapy (HAART) are excluded from the
study because of possible pharmacokinetic interactions.
- Second malignancy within the past 3 years (excluding nonmelanoma skin cancer and in
situ cancers) that has not been treated with curative intent and is not currently
without evidence of disease,
- Patients with known gastrointestinal malabsorption syndromes are excluded as this
concurrent illness will affect absorption of the oral medications.