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

Study Overview

• Status: Completed
• Conditions: Hilar Cholangiocarcinoma; Recurrent Gallbladder Carcinoma; Unresectable Extrahepatic Bile Duct Carcinoma; Unresectable Gallbladder Carcinoma; Gallbladder Adenocarcinoma; Recurrent Extrahepatic Bile Duct Carcinoma; Extrahepatic Bile Duct Adenocarcinoma; Gallbladder Adenocarcinoma With Squamous Metaplasia; Undifferentiated Gallbladder Carcinoma
• Intervention / Treatment: Drug: Erlotinib Hydrochloride; Drug: Sorafenib Tosylate

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • The University of Arizona Medical Center-University Campus
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Marysville, California, United States, 95901
      • Fremont - Rideout Cancer Center
    • Novato, California, United States, 94945
      • Sutter Cancer Research Consortium
    • Orange, California, United States, 92868
      • UC Irvine Health/Chao Family Comprehensive Cancer Center
    • Pleasanton, California, United States, 94588
      • Valley Medical Oncology Consultants
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
  • Colorado
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Saint Francis Hospital and Medical Center
  • Florida
    • Orlando, Florida, United States, 32806
      • UF Cancer Center at Orlando Health
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
    • Savannah, Georgia, United States, 31404
      • Memorial University Medical Center
  • Hawaii
    • Aiea, Hawaii, United States, 96701
      • Pali Momi Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96817
      • The Cancer Center of Hawaii-Liliha
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
    • Honolulu, Hawaii, United States, 96813
      • Oncare Hawaii Inc-POB II
    • Honolulu, Hawaii, United States, 96817
      • Oncare Hawaii Inc-Kuakini
    • Wailuku, Hawaii, United States, 96793
      • Maui Memorial Medical Center
  • Illinois
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Central Illinois CCOP
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Springfield, Illinois, United States, 62781-0001
      • Memorial Medical Center
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • Saint Francis Hospital and Health Centers
    • Richmond, Indiana, United States, 47374
      • Reid Hospital and Health Care Services
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67901
      • Cancer Center of Kansas-Liberal
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Overland Park, Kansas, United States, 66209
      • Menorah Medical Center
    • Overland Park, Kansas, United States, 66213
      • Saint Luke's South Hospital
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas - Parsons
    • Prairie Village, Kansas, United States, 66208
      • Kansas City CCOP
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas - Pratt
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Shawnee Mission, Kansas, United States, 66204
      • Shawnee Mission Medical Center
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67208
      • Associates In Womens Health
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Main Office
    • Wichita, Kansas, United States, 67214
      • Via Christi Regional Medical Center
    • Wichita, Kansas, United States, 67214
      • Wichita CCOP
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium CCOP
    • Dearborn, Michigan, United States, 48124
      • Oakwood Hospital and Medical Center
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • Flint, Michigan, United States, 48502
      • Hurley Medical Center
    • Flint, Michigan, United States, 48532
      • Genesys Regional Medical Center-West Flint Campus
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
    • Livonia, Michigan, United States, 48154
      • Saint Mary Mercy Hospital
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Saint Joseph Mercy Port Huron
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital-Royal Oak
    • Saginaw, Michigan, United States, 48601
      • Saint Mary's of Michigan
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64116
      • North Kansas City Hospital
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center
    • Kansas City, Missouri, United States, 64118
      • Heartland Hematology and Oncology Associates Incorporated
    • Kansas City, Missouri, United States, 64114
      • Saint Joseph Health Center
    • Lee's Summit, Missouri, United States, 64086
      • Saint Luke's East - Lee's Summit
    • Liberty, Missouri, United States, 64068
      • Liberty Hospital
    • Saint Joseph, Missouri, United States, 64506
      • Heartland Regional Medical Center
  • Montana
    • Billings, Montana, United States, 59101
      • Saint Vincent Healthcare
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • Montana Cancer Consortium CCOP
    • Billings, Montana, United States, 59102
      • Frontier Cancer Center and Blood Institute-Billings
    • Billings, Montana, United States, 59107
      • Billings Clinic Cancer Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Cancer Center
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Great Falls, Montana, United States, 59405
      • Berdeaux, Donald MD (UIA Investigator)
    • Helena, Montana, United States, 59601
      • Saint Peter's Community Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology PLLC
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
    • Missoula, Montana, United States, 59801
      • Community Medical Hospital
    • Missoula, Montana, United States, 59802
      • Montana Cancer Specialists
  • North Carolina
    • Gastonia, North Carolina, United States, 28054
      • Gaston Memorial Hospital
    • Hendersonville, North Carolina, United States, 28791
      • Margaret R Pardee Memorial Hospital
    • Winston-Salem, North Carolina, United States, 27104
      • Southeast Cancer Control Consortium
  • Ohio
    • Bellefontaine, Ohio, United States, 43311
      • Mary Rutan Hospital
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health Center West
    • Columbus, Ohio, United States, 43215
      • Columbus CCOP
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Health Center
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45420
      • Dayton CCOP
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Marietta, Ohio, United States, 45750
      • Marietta Memorial Hospital
    • Mount Vernon, Ohio, United States, 43050
      • Knox Community Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Hospital
    • Springfield, Ohio, United States, 45505
      • Springfield Regional Medical Center
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Westerville, Ohio, United States, 43081
      • Saint Ann's Hospital
    • Wilmington, Ohio, United States, 45177
      • Clinton Memorial Hospital
    • Xenia, Ohio, United States, 45385
      • Greene Memorial Hospital
    • Zanesville, Ohio, United States, 43701
      • Genesis Healthcare System
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Hospital
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Wellmont Holston Valley Hospital and Medical Center
  • Washington
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Bremerton, Washington, United States, 98310
      • Harrison HealthPartners Hematology and Oncology-Bremerton
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Mount Vernon, Washington, United States, 98274
      • Skagit Valley Hospital
    • Poulsbo, Washington, United States, 98370
      • Harrison HealthPartners Hematology and Oncology-Poulsbo
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98104
      • Minor and James Medical PLLC
    • Seattle, Washington, United States, 98112
      • Group Health Cooperative-Seattle
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98122
      • The Polyclinic
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology and Oncology PS
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital and Clinics
  • Wyoming
    • Casper, Wyoming, United States, 82609
      • Rocky Mountain Oncology
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (sorafenib tosylate and 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.	Drug: Erlotinib Hydrochloride; Given PO; Other Names: Cp-358,774; Tarceva; OSI-774; Drug: Sorafenib Tosylate; Given PO; Other Names: BAY 54-9085; Nexavar; BAY 43-9006 Tosylate; sorafenib

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: March 24, 2010
• First Submitted That Met QC Criteria: March 24, 2010
• First Posted (Estimate): March 25, 2010

Study Record Updates

• Last Update Posted (Estimate): June 30, 2015
• Last Update Submitted That Met QC Criteria: June 3, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Digestive System Neoplasms; Gallbladder Diseases; Biliary Tract Diseases; Bile Duct Diseases; Biliary Tract Neoplasms; Neoplasms, Ductal, Lobular, and Medullary; Carcinoma; Recurrence; Adenocarcinoma; Cholangiocarcinoma; Klatskin Tumor; Gallbladder Neoplasms; Carcinoma, Ductal; Metaplasia; Bile Duct Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride; Sorafenib
• Other Study ID Numbers: NCI-2011-02027 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA032102 (U.S. NIH Grant/Contract); SWOG-S0941; CDR0000668246; S0941 (Other Identifier: CTEP)