Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Rare Diseases

Recurrence

Carcinoma

Cholangiocarcinoma

Adenocarcinoma

Klatskin Tumor

Carcinoma, Ductal

Metaplasia

Gallbladder Neoplasms

Bile Duct Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Gallbladder Diseases

Bile Duct Diseases

Bile Duct Cancer

Gallbladder Cancer

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Sorafenib

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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.

Sorafenib Tosylate

Anthony El-Khoueiry

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.

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

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.

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.

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.

Only adverse events that are possibly, probably or definitely related to study drug are reported.

National Cancer Institute (NCI)

Patients receive sorafenib tosylate 400 mg PO twice daily and erlotinib hydrochloride 100 mg PO once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Sorafenib and Erlotinib

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Zubrod Performance Status Scale: 0 - Fully active, able to carry on all pre-disease performance without restriction; 1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light sedentary nature; 2 - Ambulatory and capable of self-care but unable to carry out any work activities; up and about more than 50% of waking hours; 3 - Capable of limited self-care, confined to bed or chair more than 50% of waking hours; 4 - Completely disabled, cannot carry on any self-care, totally confined to bed or chair

Zubrod Performance Status

Chemotherapy, multiple agents

Prior Surgery

Distant Metastatic

Locally Advanced

Current Status of Disease

Gallbladder

Primary Cancer

Prior Radiation Therapy

Adjuvant

Neoadjuvant

None

Setting of Prior Chemotherapy

Eligible patients who began protocol therapy

The first stage of accrual was met with 40 registered patients. Insufficient number of patients were alive and free from progression at four months to warrant accruing to a second stage.

Study Statistician

Overall Survival

Progression-free Survival

Objective Response

Abdominal pain

Alanine aminotransferase increased

Alkaline phosphatase increased

Allergic reaction

Aspartate aminotransferase increased

Blood bilirubin increased

Death NOS

Dehydration

Diarrhea

Erythema multiforme

Fatigue

Gastric perforation

Hepatic failure

Hepatic infection

Hepatic necrosis

Hypertension

Hypoalbuminemia

Hypokalemia

Hypophosphatemia

Hypoxia

Lymphocyte count decreased

Mucositis oral

Nausea

Pain

Palmar-plantar erythrodysesthesia syndrome

Platelet count decreased

Rash acneiform

Rash maculo-papular

Thromboembolic event

Eligible patients who received any treatment and were assessed for toxicity were included in the adverse event summaries. Any CTCAE v4.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.

Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Sorafenib Tosylate and Erlotinib Hydrochloride in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gallbladder Cancer or Cholangiocarcinoma	NCT01093222	Extrahepatic Bi... Gallbladder Ade... Gallbladder Ade... Hilar Cholangio... Recurrent Extra... Recurrent Gallb... Undifferentiate... Unresectable Ex... Unresectable Ga...	Erlotinib Hydro... Sorafenib Tosyl...	18 Years -	National Cancer Institute (NCI)
Sorafenib Tosylate and Erlotinib Hydrochloride in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gallbladder Cancer or Cholangiocarcinoma	NCT01093222	Extrahepatic Bi... Gallbladder Ade... Gallbladder Ade... Hilar Cholangio... Recurrent Extra... Recurrent Gallb... Undifferentiate... Unresectable Ex... Unresectable Ga...	Erlotinib Hydro... Sorafenib Tosyl...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for undifferentiated gallbladder carcinoma