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Metastatic Pancreatic CancerPhase 2NCT00326911

Cetuximab and Bevacizumab With or Without Gemcitabine to Treat Metastatic Pancreatic Cancer

A Phase 2 study testing cetuximab, bevacizumab and gemcitabine in people with Metastatic Pancreatic Cancer, run by Eli Lilly and Company at 16 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Eligible patients with metastatic pancreatic cancer will be treated with dual agent monoclonal antibody consisting of cetuximab and bevacizumab alone or in combination with gemcitabine Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Pancreatic Cancer
What is being tested?
cetuximab, bevacizumab and gemcitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
16 sitesUnited States
Study dates
May 2006to Dec 2008
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

  • The patient has provided signed written informed consent.
  • The patient is ≥18 years of age.
  • The patient has histologically or cytologically-confirmed pancreatic adenocarcinoma not amenable to curative treatment with surgery or has documented or suspected extrapancreatic metastases.
  • The patient has either (a) measurable disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST) or (b) non-measurable disease with an elevated baseline CA19-9 level (≥2 x the upper limit of normal [ULN]).
  • The patient's Eastern Cooperative Oncology Group (ECOG) performance status is ≤2.
  • The patient has adequate hematologic function as defined by an absolute neutrophil count (ANC) ≥1500/mm3 and a platelet count ≥100,000/mm3 obtained within 2 weeks prior to the first dose of study medication.
Show all 16Show fewer
  • The patient has adequate hepatic function as defined by a total bilirubin ≤2.0 mg/dL and transaminases ≤5.0 x ULN obtained within 2 weeks prior to the first dose of study medication.
  • The patient has adequate renal function as defined by serum creatinine ≤2.0 x ULN and urine dipstick for proteinuria ≤1+ obtained within 2 weeks prior to the first dose of study medication. If urine dipstick is ≥2+, then a 24-hour urine for protein must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study. Urinalysis is also acceptable.
  • If the patient is on full-dose anticoagulation therapy (eg, warfarin or low molecular weight [LMW] heparin), the following criteria must be met:
  • The patient has an in-range International Normalized Ratio ([INR]usually between 2 and 3) on a stable dose of oral anticoagulant or be on a stable dose of LMW heparin
  • The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  • If the patient is not on full-dose anticoagulation therapy, the following criteria must be met:
  • The patient has adequate coagulation function as defined by INR ≤1.5
  • The patient has a partial thromboplastin (PTT) ≤ULN obtained within 2 weeks prior to the first dose of study medication
  • If a woman, the patient agrees to use an accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the study. If a male and sexually active, the patient agrees to use effective contraception.
  • The patient is accessible for treatment and follow-up. Patients enrolled in this trial must be treated at the participating center.

Who cannot join

  • Endocrine tumors or lymphoma of the pancreas
  • Known brain metastases
  • Prior therapy with an epidermal growth factor receptor (EGFR) inhibitor or vascular endothelial growth factor (VEGF) inhibitor
  • Prior chemotherapy, hormonal therapy, or radiation therapy for advanced pancreatic cancer, patients who received chemotherapy and/or radiation therapy in the adjuvant setting will be eligible as long as the adjuvant therapy was completed >6 months prior
  • Concurrent malignancy other than non-melanomatous skin cancer or carcinoma in situ of the cervix
  • Concurrent treatment with other anti-cancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemoembolization, or targeted therapy
Show all 14Show fewer
  • Ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations
  • History of arterial thrombotic events within 9 months
  • History of uncontrolled hypertension (>150/100 mmHg) not on a stable regimen of anti-hypertensive therapy
  • History of significant bleeding events or upper or lower gastrointestinal bleeding within 9 months
  • History of gastrointestinal perforation within 12 months
  • Serious non-healing wound ulcer, bone fracture, or major surgical procedure with 28 days
  • If a woman, is pregnant or lactating
  • An employee of the investigator or study center as well as family members of the employees

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

United States16 sites
  • ImClone Investigational Site

    Arlington, Texas, 76012

  • ImClone Investigational Site

    Atlanta, Georgia, 30309

  • ImClone Investigational Site

    Augusta, Georgia, 30901

  • ImClone Investigational Site

    Billings, Montana, 59101

  • ImClone Investigational Site

    Charleston, South Carolina, 29406

  • ImClone Investigational Site

    Concord, North Carolina, 28025

  • ImClone Investigational Site

    Dallas, Texas, 75230

  • ImClone Investigational Site

    Jonesboro, Arkansas, 72401

  • ImClone Investigational Site

    Marietta, Georgia, 30060

  • ImClone Investigational Site

    Metairie, Louisiana, 70006

  • ImClone Investigational Site

    Miami, Florida, 33176

  • ImClone Investigational Site

    Orlando, Florida, 32804

  • ImClone Investigational Site

    Orlando, Florida, 32806

  • ImClone Investigational Site

    Philadelphia, Pennsylvania, 19106

  • ImClone Investigational Site

    San Francisco, California, 94115

  • ImClone Investigational Site

    Stamford, Connecticut, 06902

Other trials in United States

About this study

Official title: A Phase II, Randomized, Open-Label Study of Cetuximab and Bevacizumab Alone or in Combination With Fixed-Dose Rate Gemcitabine as First-Line Therapy of Patients With Metastatic Adenocarcinoma of the Pancreas

Eligible patients with metastatic pancreatic cancer will be treated with dual agent monoclonal antibody consisting of cetuximab and bevacizumab alone or in combination with gemcitabine

Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cetuximabBiological

    Also called Erbitux®

    I.V. infusion of 400 mg/m2 (over 120 minutes) on day 1 of cycle 1

  • bevacizumabBiological

    Also called Avastin®

    10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks.

  • gemcitabineDrug

    Also called Gemzar®

    1000 mg/m2 administered intravenously at 10 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks.

  • cetuximabBiological

    Also called Erbitux®

    I.V.infusions of 250 mg/m2 (over 60 minutes) weekly

Study groups in NCT00326911
Study groupRoleWhat they receive
cetuximab + bevacizumab + gemcitabineExperimentalCetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. All medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
Receives: Biological: cetuximab; Biological: bevacizumab; Drug: gemcitabine
cetuximab + bevacizumabActive comparatorCetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
Receives: Biological: cetuximab; Biological: bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS)

    Progression-free survival is the time from randomization until the date of progressive disease (PD) or death from any cause whichever is first reported. Patients who die without a reported prior progression were considered to have progresssed on the day of their death. Patients who did not progress were censored at the day of their last tumor assessment.

    Measured: Time from randomization to disease progression or death from any cause (Range: 0 -10 months)

Secondary outcomes (22)
  1. Overall Survival (OS)

    This measure is defined as the time from randomization to the date of death due to any cause. Survival of living patients or those who lost to follow-up were censored on the last date the patients were known to be alive.

    Measured: Survival information was collected continuously every 3 months after completion of therapy and/or follow-up (range: 1-19 months).

  2. The Number of Patients With a Best Overall Response of Either a Complete Response (CR) or Partial Response (PR)

    The best overall response is the number of patients with a best overall response of CR or PR, as classifed by the investigator according to the RECIST guidelines. A CR is the disappearance of all target lesions and a PR is at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter.

    Measured: Tumor evaluations were performed every 8 weeks while on cetuximab therapy until PD or recurrence. Patients with a PR or CR had a confirmatory tumor assessment no less than 4 weeks after the initial evaluation.

  3. Percentage of Patients With Carbohydrate Antigen 19-9 (CA19-9) Response at End of Cycle 2 in Patients With Elevated Baseline Values (Equal or Greater Than 2 x Upper Limit of Normal).

    CA19-9 is a tumor marker for pancreatic cancer and the level usually increases as the disease is progressing. The CA19-9 response was the percentage of patients whose CA19-9 level was declining, stable or increasing < 10% compared with baseline, divided by the total patients with elevated baseline CA19-9 in that arm.

    Measured: First day of treatment to the end of Cycle 2, Week 1

  4. Time to Progression (TTP)

    Time to progression was defined as the time from randomization until the date of objectively confirmed tumor progression was first reported. The censoring rule was consistent with PFS except death. Patients who died from any cause were censored at the time of death or at last tumor assessment date if the death date was missing. For patients lost to follow-up, they were censored at the last tumor assessment date.

    Measured: Time from randomization until the date of objective tumor progression was first reported (range: 11 -38 months)

  5. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Reported AEs per patient were coded according to the corresponding preferred term and system organ class in the Medical Dictionary for regulatory Activities dictionary. The National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0 was used to grade all AEs. The collection of AEs began at the time the patient received the first cetuximab dose and continued during the study until 30 days after the last dose of cetuximab. All patients who were enrolled and treated with cetuximab were assessed for safety (mITT population, as treated).

    Measured: An AE was included in the safety analysis if its onset date occurred anytime during cetuximab treatment or up to 30 days after the last dose of cetuximab.

  6. Change From Baseline in Quality of Life (QoL) Assessment Using the Linear Analog Scale Assessment (LASA), Overall QoL at Cycle 2 Week 4

    Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Overall QoL question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

    Measured: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

  7. Change From Baseline in QoL Assessment Using LASA, Overall Mental Well Being, at Cycle 2 Week 4

    Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Overall Mental Well Being question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

    Measured: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

  8. Change From Baseline in QoL Assessment Using LASA, Overall Physical Well Being, at Cycle 2 Week 4

    Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Overall Physical Well Being question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

    Measured: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

  9. Change From Baseline in QoL Assessment Using LASA, Overall Emotional Well Being, at Cycle 2 Week 4

    Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Overall Emotional Well Being question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

    Measured: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

  10. Change From Baseline in QoL Assessment Using LASA, Level of Social Activity, at Cycle 2 Week 4

    Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Level of Social Activity question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

    Measured: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

  11. Change From Baseline in QoL Assessment Using LASA, Overall Spiritual Well Being, at Cycle 2 Week 4

    Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Overall Spiritual Well Being question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

    Measured: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up while receiving study drug

  12. Change From Baseline in QoL Assessment Using LASA, Frequency of Pain, at Cycle 2 Week 4

    Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Frequency of Pain question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates improvement from baseline.

    Measured: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

  13. Change From Baseline in QoL Assessment Using LASA, Severity of Pain, Average, at Cycle 2 Week 4

    Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Severity of Pain question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A positive score indicates improvement from baseline.

    Measured: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up while receiving study drug

  14. Change From Baseline in QoL Assessment Using LASA, Level of Fatigue, Average, at Cycle 2 Week 4

    Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Level of Fatigue question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A positive score indicates improvement from baseline.

    Measured: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

  15. Change From Baseline in QoL Assessment Using LASA, Level of Support, Friends and Family, at Cycle 2 Week 4

    Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Level of Support, Friends and Family question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

    Measured: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

  16. Change From Baseline in QoL Assessment Using LASA, Financial Concerns, at Cycle 2 Week 4

    Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Financial Concerns Question question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

    Measured: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

  17. Change From Baseline in QoL Assessment Using LASA, Legal Concerns, at Cycle 2 Week 4

    Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Legal Concerns question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

    Measured: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

  18. Change From Baseline in Assessment of Pain Using the Brief Pain Inventory (BPI) Short Form, Worst Pain, at Cycle 2 Week 4

    Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. Analysis of pain using the BPI was considered exploratory. The Worst Pain (change from baseline) to Cycle 2 Week 4 is reported. The worst pain is 10 and no pain is 0. A negative score indicates improvement from baseline.

    Measured: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

  19. Change From Baseline in Assessment of Pain Using BPI Short Form, Least Pain, at Cycle 2 Week 4

    Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. Analysis of pain using the BPI was considered exploratory. The Least Pain (change from baseline) to Cycle 2 Week 4 is reported. The worst pain is 10 and no pain is 0. A negative score indicates improvement from baseline.

    Measured: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

  20. Change From Baseline in Assessment of Pain Using BPI Short Form, Average Pain, at Cycle 2 Week 4

    Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. Analysis of pain using the BPI was considered exploratory. The Average Pain (change from baseline) to Cycle 2 Week 4 is reported. The worst pain was 10 and no pain is 0. A negative score indicates improvement from baseline.

    Measured: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

  21. Change From Baseline in Assessment of Pain Using BPI Short Form, Pain Right Now, at Cycle 2 Week 4

    Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. Analysis of pain using the BPI was considered exploratory. The Pain Right Now question (change from baseline) to Cycle 2 Week 4 is reported. The worst pain is 10 and no pain is 0. A negative score indicates improvement from baseline.

    Measured: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

  22. Change From Baseline in Assessment of Pain Using BPI Short Form, Interference, at Cycle 2 Week 4

    Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. Analysis of pain using the BPI was considered exploratory. The Interference question (change from baseline) to Cycle 2 Week 4 is reported. Complete interference is scored as 10 and no interference is scored as 0. A negative score indicates improvement from baseline.

    Measured: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2006 (estimated)
  2. Study startMay 2006
  3. Primary completionOct 2008
  4. Study completionDec 2008

Why it stopped: The planned enrollment was 130 patients and the study was halted prematurely due to lack of efficacy in both arms. Enrolled patients continued treatment.

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00326911
Sponsor's protocol ID
CP02-0555
Status last verified
May 2011
First submitted
15 May 2006
Last updated
25 May 2011
Data monitoring committee
Yes

Publications

  • Ko AH, Youssoufian H, Gurtler J, Dicke K, Kayaleh O, Lenz HJ, Keaton M, Katz T, Ballal S, Rowinsky EK. A phase II randomized study of cetuximab and bevacizumab alone or in combination with gemcitabine as first-line therapy for metastatic pancreatic adenocarcinoma. Invest New Drugs. 2012 Aug;30(4):1597-606. doi: 10.1007/s10637-011-9691-8. Epub 2011 Jun 1.

    PubMed 21629990

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing cetuximab, bevacizumab and gemcitabine in people with Metastatic Pancreatic Cancer, run by Eli Lilly and Company at 16 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 16 inclusion and 14 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: stopped early, as of the sponsor's last update on 25 May 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 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 4 Dec 2009). 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?

Progression-free Survival (PFS) (time frame: Time from randomization to disease progression or death from any cause (Range: 0 -10 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 NCT00326911, which also lists 1 linked publication.

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 25 May 2011.

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