Clinical trial NCT00987766: Gemcitabine Hydrochloride, Oxaliplatin, and Erlotinib Hydrochloride in Treating Patients With Advanced Biliary Tract Cancer, Pancreatic Cancer, Duodenal Cancer, or Ampullary Cancer
Official title: Phase Ib Trial of Gemcitabine and Oxaliplatin (GEMOX) With Erlotinib in Patients With Advanced Biliary Tract Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Extrahepatic Bile Duct Cancer
Gallbladder Cancer
Liver Cancer
Pancreatic Cancer
Periampullary Adenocarcinoma
Small Intestine Cancer
Keywords: advanced adult primary liver cancer
stage III pancreatic cancer
stage IV pancreatic cancer
periampullary adenocarcinoma
small intestine adenocarcinoma
adenocarcinoma of the extrahepatic bile duct
adenocarcinoma of the gallbladder
unresectable extrahepatic bile duct cancer
unresectable gallbladder cancer
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-10-01
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine hydrochloride and oxaliplatin together with erlotinib hydrochloride may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of erlotinib hydrochloride when given together with gemcitabine hydrochloride and oxaliplatin in treating patients with advanced biliary tract cancer, pancreatic cancer, duodenal cancer, or ampullary cancer.

Detailed description: OBJECTIVES:

Primary

* To determine the maximum tolerated dose and the recommended phase II dose of erlotinib hydrochloride in combination with gemcitabine hydrochloride and oxaliplatin in patients with advanced biliary tract cancer, pancreatic cancer, duodenal cancer, or ampullary cancer.

Secondary

* To describe any antitumor activity associated with this treatment regimen when given during the dose-escalation and expanded-cohort portions of this study.
* To evaluate e-cadherin, vimentin, fibronectin, amphiregulin, and Kras status in the tumors and assess their relationship to response.

OUTLINE: This is a multicenter, dose-escalation study of erlotinib hydrochloride.

Patients receive gemcitabine hydrochloride IV on day 1, oxaliplatin IV over 2 hours on day 2, and oral erlotinib hydrochloride once daily on days 3-8. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

Tumor tissue samples are collected for biomarker and other analysis.

After completion of study treatment, patients are followed up for 30 days.

Eligibility criteria: Inclusion Criteria:

* Only advanced carcinomas defined as unresectable or metastatic that are histologically or cytologically confirmed to be biliary tract, pancreas, duodenal, or ampullary carcinomas will be included.
* Dose-escalation: Patients \> 18 years of age with biopsy-confirmed advanced biliary tract adenocarcinoma, pancreas cancer, duodenal cancer, or ampullary cancer
* MTD expansion cohort: Patients \> 18 years of age with biopsy-confirmed advanced biliary tract adenocarcinoma only.
* No prior chemotherapy or prior EGF receptor inhibitor therapy
* Measurable tumor by imaging examination
* Performance status (PS) 0-2 on the ECOG performance scale
* Have pretreatment bilirubin\<2.5x upper limit of normal (ULN), serum creatinine\<1.5x ULN, AST and ALT \<2.5xULN or in the presence of liver metastasis \<5xULN, neutrophils\>1500, platelets\>100K, hemoglobin \>9 g/dL
* Patients - both males and females - with reproductive potential (ie, menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration.
* Have the ability to understand the requirements of the study and provide informed consent

Exclusion Criteria:

* CNS metastases
* Uncontrolled infection
* Pregnant or nursing women may not participate.
* No other prior malignancy is allowed except for the following: 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 for 5 years.
* Psychiatric illness that would prevent understanding the nature of the investigational therapy and complying with protocol requirements
* Patients with \> grade 2 neuropathy
* Patients with \> grade 2 uncontrolled nausea and vomiting despite antiemetics
* Any concurrent medical condition that, in the judgment of the investigator, would make the patient an inappropriate candidate for study enrollment
* Prior chemotherapy or EGFR inhibitor

Primary outcomes:
measure: Maximum tolerated dose and recommended phase II dose of erlotinib hydrochloride in combination with gemcitabine hydrochloride and oxaliplatin
timeFrame: 28 days
Secondary outcomes:
measure: Antitumor activity
timeFrame: 30 days after completing treatment.
measure: E-cadherin, vimentin, fibronectin, amphiregulin, and Kras status in the tumors and their relationship to response
timeFrame: 30 days after completing treatment.
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Laura Goff, MD
role: PRINCIPAL_INVESTIGATOR
References: