Study Of Gemcitabine And Erlotinib Plus Sorafenib (GES) In Metastatic Pancreatic Cancer

Study Overview

Study of Gemcitabine and Erlotinib Plus Sorafenib (GES) in Metastatic Pancreatic Cancer

This study tests the combination of two targeted therapies,along with chemotherapy treatment in the treatment of pancreatic cancer.

Until very recently, additional therapies in pancreatic cancer have targeted either the vascular endothelial growth factor (VEGF) or epidermal growth factor (EGF) pathways, a strategy which has shown variable clinical efficacy. This inconsistency is not surprising, given the knowledge that tumors have a certain level of signal redundancy which may limit the effectiveness of any one single-targeted therapy. The dual blockade of the EGF and VEGF pathways takes aim at two of the most active cascades in tumorigenesis. Preliminarily, a phase II study done in pancreatic cancer with gemcitabine, bevacizumab and erlotinib or cetuximab has shown promising results and will most likely proceed to phase III study for definitive efficacy assessment (Kindler et al, 2006). In this study, targeted blockade is carried one step further with the inhibition of the signaling cascade downstream of receptor tyrosine kinases at the level of raf. Given the fact that the majority of pancreatic tumors display constitutive activation of the Ras/Raf/MEK/ERK pathway, it is hoped that the addition of sorafenib to gemcitabine and erlotinib will obtain a more complete blockade of the signal transduction cascade responsible for pancreatic tumor growth and progression.

Pancreatic Cancer

DRUG: Gemcitabine
DRUG: Erlotinib
DRUG: Sorafenib

NYU 06-882

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2008-06-11	Results First Submitted 2011-11-18	Last Update Submitted that met QC Criteria 2016-05-31
First Submitted that Met QC Criteria 2008-06-12	Results First Submitted that Met QC Criteria 2011-11-18	Last Update Posted (ESTIMATED) 2016-06-30
First Posted (ESTIMATED) 2008-06-13	Results First Posted 2011-12-21	Last Verified 2016-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Combination GES Combination of Gemcitabine, Erlotinib, and Sorafenib	DRUG: Gemcitabine 1000 mg/m^2, intravenous, Days 1, 8, 15 for every 28-day cycle. In the absence of disease progression or toxicity, a patient may continue to receive gemcitabine, erlotinib, and sorafenib until disease progression. DRUG: Erlotinib 150 mg, taken orally, once a day, Days 1-28 for every 28-day cycle. In the absence of disease progression or toxicity, a patient may continue to receive gemcitabine, erlotinib, and sorafenib until disease progression. DRUG: Sorafenib 400 mg, taken orally, twice a day, Days 1-28 for every 28-day cycle. In the absence of disease progression or toxicity, a patient may continue to receive gemcitabine, erlotinib, and sorafenib until disease progression.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Combination GES

Combination of Gemcitabine, Erlotinib, and Sorafenib

DRUG: Gemcitabine

1000 mg/m^2, intravenous, Days 1, 8, 15 for every 28-day cycle. In the absence of disease progression or toxicity, a patient may continue to receive gemcitabine, erlotinib, and sorafenib until disease progression.

DRUG: Erlotinib

150 mg, taken orally, once a day, Days 1-28 for every 28-day cycle. In the absence of disease progression or toxicity, a patient may continue to receive gemcitabine, erlotinib, and sorafenib until disease progression.

DRUG: Sorafenib

400 mg, taken orally, twice a day, Days 1-28 for every 28-day cycle. In the absence of disease progression or toxicity, a patient may continue to receive gemcitabine, erlotinib, and sorafenib until disease progression.

Primary Outcome Measures	Measure Description	Time Frame
4-month Progression Free Survival (PFS) Rate	The PFS rate at 4 months is defined as the percentage of patients whose disease is progression free at 4 months from the start of treatment. Disease progression is evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) (Therasse et al, 2000). Radiological measurements to determine progression is performed every 2 cycles.	4 months

Secondary Outcome Measures	Measure Description	Time Frame
Objective Response Rate	The response rate is the percentage of the patients who have a complete response or partial response based on RECIST from the start of the treatment. The response is evaluated every 2 cycles by radiologic methods (e.g., computer tomography (CT)).	up to 1 year
Median Overall Survival (mOS)	Median overall survival is defined as the time when 50% of the patients are alive from the start of the treatment.	up to 2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically or cytologically confirmed pancreatic adenocarcinoma not amenable to curative treatment with surgery. Patients with locally advanced disease must have disease that extends outside the boundaries of a standard radiation port.
Measurable disease, as defined by Response Evaluation Criteria In Solid Tumors (RECIST). This requires at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. Pleural effusions and ascites are not considered measurable lesions.
No prior cytotoxic chemotherapy for metastatic disease. Prior adjuvant chemotherapy is allowed, however at least 6 months must have elapsed from administration of the last dose of chemotherapy or radiotherapy.
No prior therapy with a VEGF, EGFR, or multi-targeted kinase inhibitor.
Age >18 years.
Life expectancy of greater than 3 months.
Eastern Cooperative Oncology Group performance status 0-1.
Normal organ and marrow function as defined below:

White blood cells (WBC) >3,000/µl
Absolute neutrophil count >1,500/µl
Platelets >100,000/µl
Total bilirubin ≤ 2.5 x institutional upper limit of normal (ULN)
Transaminases(SGOT/ SGPT)

without liver mets ≤ 2.5 x institutional ULN
with liver mets ≤ 5 x institutional ULN
International Normalized Ratio (INR)

patients not on warfarin ≤ 1.5
patients on warfarin ≤ 3
Renal Function: Serum creatinine ≤ 1.5 xULN
Proteinuria: Urine protein <1+, or 24hr urine protein <500 mg
At least 30 days since receiving any investigational drug.
Patients who received prior radiation therapy must have a site of measurable disease that is not located within the prior radiation port.
Patients who are on warfarin anticoagulation are allowed to participate as long as they fit the following 3 criteria:

They are therapeutic on a stable warfarin dose
Their INR target range is no greater than 3
They are monitored with regular INR testing
Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
Women of childbearing potential and men must agree to use adequate contraception (barrier method birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least three months after the last administration of study drugs.
Ability to understand and the willingness to sign a written informed consent document.

No prior treatment with bevacizumab, cetuximab, or erlotinib. Prior gemcitabine in the adjuvant setting completed more than six months previously will be allowed.
No other investigational agents.
No central nervous system (CNS) disease, including primary brain tumors, brain metastasis, or history of a cerebro-vascular accident (CVA) or transient ischemic attack (TIA) within 6 months of starting therapy.
No allergic reactions to compounds similar to erlotinib or sorafenib.
Because an increased risk of bleeding may occur following sorafenib administration, no patients will be allowed with a history of bleeding diathesis or coagulopathy. No grade > 2 pulmonary hemorrhage or > grade 3 other hemorrhage within 28 days of beginning therapy.
No recent invasive procedures defined as follows: Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 of therapy
No Patients with clinically significant cardiovascular disease, defined as:

Uncontrolled hypertension
Myocardial infarction < 6 months prior to registration and new onset angina within 3 months (controlled stable angina acceptable)
New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris
Grade II or greater peripheral vascular disease
No serious or non-healing wound, ulcer, or bone fracture.
No active infection requiring parental antibiotics.
No currently active second malignancy other than non-melanoma skin cancer or carcinoma in-situ of the cervix.
If a patient is on full-dose anticoagulants (warfarin or low molecular weight heparins are allowed), the following criteria should be met for enrollment: they must have a therapeutic INR, no greater than 3, on a stable dose of warfarin.
No use of thrombolytic agents within 1 month of study initiation.
No gastrointestinal tract disease resulting in an inability to take oral medication or prior surgical procedures affecting absorption. This may include patients with or without requirements for IV alimentation.
No women who are pregnant (positive pregnancy test) or nursing. Fertile men and women must agree to use adequate contraceptive measures during study therapy and for at least 3 months after the completion of antibody therapy.
Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, no HIV-positive patients, including those receiving combination anti-retroviral therapy, are allowed on the study.
Any condition that impairs patient's ability to swallow whole pills
Any malabsorption problem

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Bayer
OSI Pharmaceuticals

Investigators

PRINCIPAL_INVESTIGATOR: Deirdre Cohen, MD, NYU School of Medicine

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Kindler HL, K. A. Bylow, H. S. Hochster, G. Friberg, K. Micetich, G. Locker, M. Kozloff, M. Moore, W. Sun, E. E. Vokes, and University Of Chicago Phase II Consortium. A randomized phase II study of bevacizumab (B) and gemcitabine (G) plus cetuximab (C) or erlotinib (E) in patients with advanced pancreatic cancer: A preliminary analysis. J. Clin. Oncol (Meeting Abstracts) June 2006, vol. 24 no. 18_suppl 4040
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.

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