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

Phase 2

Completed

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

Interventions: Drug: Erlotinib Hydrochloride
Drug: Sorafenib Tosylate

Registration Number: NCT01093222

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 40

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (sorafenib tosylate and erlotinib hydrochloride)	Sorafenib Tosylate	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.
Treatment (sorafenib tosylate and erlotinib hydrochloride)	Erlotinib Hydrochloride	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.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	Up to 3 years	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Up to 3 years	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.
Objective Response	Up to 3 years	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.
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug	Up to 3 years	Only adverse events that are possibly, probably or definitely related to study drug are reported.

Trial Locations

Locations (141): The University of Arizona Medical Center-University Campus
🇺🇸
Tucson, Arizona, United States
Loma Linda University Medical Center
🇺🇸
Loma Linda, California, United States
USC / Norris Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
Fremont - Rideout Cancer Center
🇺🇸
Marysville, California, United States
Sutter Cancer Research Consortium
🇺🇸
Novato, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
🇺🇸
Orange, California, United States
Valley Medical Oncology Consultants
🇺🇸
Pleasanton, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸
Sacramento, California, United States
Poudre Valley Hospital
🇺🇸
Fort Collins, Colorado, United States
Saint Francis Hospital and Medical Center
🇺🇸
Hartford, Connecticut, United States
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The University of Arizona Medical Center-University Campus
🇺🇸Tucson, Arizona, United States