Sorafenib Tosylate and Erlotinib Hydrochloride in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gallbladder Cancer or Cholangiocarcinoma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase II Study of Sorafenib (NSC-724772) and Erlotinib (NSC-718781) in Patients With Advanced Gallbladder Carcinoma or Cholangiocarcinoma

Conditions
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Extrahepatic Bile Duct Adenocarcinoma, Gallbladder Adenocarcinoma, Gallbladder Adenocarcinoma With Squamous Metaplasia, Hilar Cholangiocarcinoma, Recurrent Extrahepatic Bile Duct Carcinoma, Recurrent Gallbladder Carcinoma, Undifferentiated Gallbladder Carcinoma, Unresectable Extrahepatic Bile Duct Carcinoma, Unresectable Gallbladder Carcinoma

Intervention / Treatment
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* Drug: Erlotinib Hydrochloride
* Drug: Sorafenib Tosylate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cytologically or pathologically confirmed gallbladder carcinoma or cholangiocarcinoma No ampullary carcinoma 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) For patient who had decompression of the biliary tree within the past 14 days, stability of the bilirubin level needs to be confirmed with two measurements within 5 to 7 days of each other 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: Myocardial infarction within the past 6 months Uncontrolled angina within the past 6 months NYHA class II-IV congestive heart failure Grade 3 cardiac valve dysfunction Cardiac arrhythmia not controlled by medication History of stroke or transient ischemic attack within the past 6 months History of arterial thrombotic event of any type in the past 6 months 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 gastrointestinal tract disease or prior abdominal surgery that results in an inability to absorb oral medication 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (sorafenib tosylate and erlotinib hydrochloride)<br>Patients receive sorafenib tosylate 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. | Drug: Erlotinib Hydrochloride<br>* Given PO<br>* Other names: Tarceva;Drug: Sorafenib Tosylate<br>* Given PO<br>* Other names: sorafenib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | From date of registration to date of first documentation of progression or symptomatic deterioration (as defined in protocol), or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact. | Up to 3 years | 
| Objective Response | Complete response (CR) is complete disappearance of all target and non-target lesions, no new lesions and no disease related symptoms. Partial response (PR) is a greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. Confirmed response is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR. | Up to 3 years | 
| Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Only adverse events that are possibly, probably or definitely related to study drug are reported. | Up to 3 years |