Pancreatic CancerPhase 2NCT00696696
Study of Gemcitabine and Erlotinib Plus Sorafenib (GES) in Metastatic Pancreatic Cancer
A Phase 2 study testing Gemcitabine, Erlotinib and Sorafenib in people with Pancreatic Cancer, run by NYU Langone Health at 3 sites in United States.
Trial summary
This study tests the combination of two targeted therapies,along with chemotherapy treatment in the treatment of pancreatic cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- Gemcitabine, Erlotinib and Sorafenib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2007to Jun 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Bellevue Hospital
New York, New York, 10016
New York University Cancer Center
New York, New York, 10016
Desert Regional Medical Center
Palm Springs, California, 92262
About this study
Official title: A Phase II 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.
Read the 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.
- Conditions
- Pancreatic Cancer
- Being tested
- Gemcitabine, Erlotinib, Sorafenib
- Keywords
- Pancreatic adenocarcinoma, metastatic, EGRF inhibitor, targeted therapy, combined cancer therapy, kinase inhibitor, VEGF-R inhibitor
- Medical subject headings
- Pancreatic Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
Also called Gemzar
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.
ErlotinibDrug
Also called Tarceva, OSI-774, CP-358
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.
SorafenibDrug
Also called Nexavar, BAY 43-9006
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.
| Study group | Role | What they receive |
|---|---|---|
| Combination GES | Experimental | Combination of Gemcitabine, Erlotinib, and Sorafenib Receives: Drug: Gemcitabine; Drug: Erlotinib; Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 months
Secondary outcomes (2)
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)).
Measured: 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.
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2008 (estimated)
- Study startSep 2007
- Primary completionNov 2010
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer, OSI Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Deirdre Cohen, MD, Principal investigator, NYU School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00696696
- Sponsor's protocol ID
- NYU 06-882
- Status last verified
- May 2016
- First submitted
- 11 Jun 2008
- Last updated
- 30 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 10655437
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Gemcitabine and Erlotinib Plus Sorafenib (GES) in Metastatic Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT00696696
- Acronym / sponsor ID
- NYU 06-882
- Conditions
- Pancreatic Cancer
- Keywords
- Pancreatic adenocarcinoma, metastatic, EGRF inhibitor, targeted therapy, combined cancer therapy, kinase inhibitor, VEGF-R inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- Bayer, OSI Pharmaceuticals
- Study start
- Sep 2007
- Primary completion
- Nov 2010 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 13 Jun 2008 (estimated)
- Results
- Posted 21 Dec 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study tests the combination of two targeted therapies,along with chemotherapy treatment in the treatment of pancreatic cancer.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination GES | Experimental | Drug: Gemcitabine, Drug: Erlotinib, Drug: SorafenibCombination of Gemcitabine, Erlotinib, and Sorafenib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GemcitabineAlso: Gemzar1000 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 | Combination GES |
| ErlotinibAlso: Tarceva, OSI-774, CP-358150 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 | Combination GES |
| SorafenibAlso: Nexavar, BAY 43-9006400 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. | Drug | Combination GES |
Primary outcome
4-month Progression Free Survival (PFS) Rate
Time frame: 4 months
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.
2 secondary outcomes
Objective Response Rate
Time frame: up to 1 year
Median Overall Survival (mOS)
Time frame: up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundKindler 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
- Background: PubMed 10655437Therasse 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deirdre Cohen, MD principal investigator
NYU School of Medicine
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gemcitabine, Erlotinib and Sorafenib in people with Pancreatic Cancer, run by NYU Langone Health at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Dec 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
4-month Progression Free Survival (PFS) Rate (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00696696, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2016.