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

This study has been completed.
Sponsor:
Collaborators:
Desert Regional Medical center
Bayer
OSI Pharmaceuticals
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT00696696
First received: June 11, 2008
Last updated: January 13, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
Pancreatic Cancer
Drug: Gemcitabine
Drug: Erlotinib
Drug: Sorafenib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Gemcitabine and Erlotinib Plus Sorafenib (GES) in Metastatic Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • 4-month Progression Free Survival (PFS) Rate [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Objective Response Rate [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
    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)).

  • Median Overall Survival (mOS) [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    Median overall survival is defined as the time when 50% of the patients are alive from the start of the treatment.


Enrollment: 45
Study Start Date: September 2007
Study Completion Date: June 2013
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other Name: Gemzar
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.
Other Names:
  • Tarceva
  • OSI-774
  • CP-358
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.
Other Names:
  • Nexavar
  • BAY 43-9006

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 document.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00696696

Locations
United States, California
Desert Regional Medical Center
Palm Springs, California, United States, 92262
United States, New York
New York University Cancer Center
New York, New York, United States, 10016
Bellevue Hospital
New York, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
Desert Regional Medical center
Bayer
OSI Pharmaceuticals
Investigators
Principal Investigator: Deirdre Cohen, MD NYU School of Medicine
  More Information

Publications:
Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT00696696     History of Changes
Other Study ID Numbers: NYU 06-882
Study First Received: June 11, 2008
Results First Received: November 18, 2011
Last Updated: January 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by New York University School of Medicine:
Pancreatic adenocarcinoma
metastatic
EGRF inhibitor
targeted therapy
combined cancer therapy
kinase inhibitor
VEGF-R inhibitor

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Erlotinib
Sorafenib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 29, 2014