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

Phase 2
18 Years
Open (Enrolling)
Pancreatic Cancer

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Trial Information

A Phase II Study of Gemcitabine and Erlotinib Plus Sorafenib (GES) in Metastatic 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.

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

4-month Progression Free Survival (PFS) Rate

Outcome Description:

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.

Outcome Time Frame:

4 months

Safety Issue:


Principal Investigator

Deirdre Cohen, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NYU School of Medicine


United States: Food and Drug Administration

Study ID:

NYU 06-882



Start Date:

September 2007

Completion Date:

March 2013

Related Keywords:

  • Pancreatic Cancer
  • Pancreatic adenocarcinoma
  • metastatic
  • EGRF inhibitor
  • targeted therapy
  • combined cancer therapy
  • kinase inhibitor
  • VEGF-R inhibitor
  • Pancreatic Neoplasms



Desert Regional Medical Center Palm Springs, California  92262
New York University Cancer Center New York, New York  10016
Bellevue Hospital New York, New York  10016