Phase II Study of Sorafenib (NSC-724772) and Erlotinib (NSC-718781) in Patients With Advanced Gallbladder Carcinoma or Cholangiocarcinoma
Phase II Study of Sorafenib (NSC-724772) and Erlotinib (NSC-718781) in Patients With Advanced Gallbladder Carcinoma or Cholangiocarcinoma
This phase II trial is studying how well giving sorafenib tosylate together with erlotinib hydrochloride works in treating patients with locally advanced, unresectable, or metastatic gallbladder cancer or cholangiocarcinoma. Sorafenib tosylate and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor.
OBJECTIVES:
I. To assess the progression-free survival in patients with unresectable or metastatic gallbladder carcinoma or cholangiocarcinoma treated with the combination of sorafenib (sorafenib tosylate) and erlotinib (erlotinib hydrochloride).
II. To assess the overall survival in patients with unresectable or metastatic gallbladder carcinoma or cholangiocarcinoma treated with the combination of sorafenib and erlotinib.
III. To assess the objective response rate. IV. To assess the frequency and severity of toxicities. V. To collect specimens for banking for future research.
OUTLINE: This is a multicenter study.
Patients receive sorafenib tosylate orally (PO) twice daily and erlotinib hydrochloride PO once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up every 6 months for 3 years.
Inclusion Criteria:
Cytologically or pathologically confirmed gallbladder carcinoma or cholangiocarcinoma
Locally advanced unresectable or distant metastatic disease
Measurable disease
Patients with biliary obstruction must have decompression of the biliary tree by ERCP and stenting or percutaneous drainage
No prior systemic treatment for metastatic or unresectable locally advanced disease
No known brain metastases
Zubrod performance status of 0-1
Leukocyte count ≥ 3,000/mm^3
ANC ≥ 1,000/mm^3
Platelet count ≥100,000/mm^3
Total serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
Serum albumin ≥ 2.5 g/dL
AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN for liver metastases)
Creatinine clearance ≥ 60 mL/min
Not pregnant or nursing
Fertile patients must agree to use effective contraception
No active biliary sepsis
No bleeding diathesis
No uncontrolled or clinically significant cardiovascular disease, including any of the following:
No uncontrolled hypertension, as evidenced by systolic BP ≥ 150 mm Hg or diastolic BP ≥ 100 mm Hg, within the past 28 days
Must be able to swallow and tolerate oral medications
No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free within the past 3 years
No concurrent grapefruit or its juice
At least 6 months since 1 adjuvant or neoadjuvant regimen of chemotherapy, hormonal therapy, immunotherapy, radiotherapy (to < 25% of bone marrow only), or chemoradiotherapy before documented recurrence or metastatic disease
No prior treatment with any antiangiogenic agent or any EGFR inhibitors for any reason
Concurrent multiple anti-hypertensive medications allowed
No plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or any other therapy, including herbal or alternative medications for treatment of cancer
Sacramento, California 95817, United States
Seattle, Washington 98109, United States