Clinical trial NCT00326911: Cetuximab and Bevacizumab With or Without Gemcitabine to Treat Metastatic Pancreatic Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Pancreatic Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2006-05-17
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: Inclusion Criteria:

* 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.
* 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.

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Time from randomization to disease progression or death from any cause (Range: 0 -10 months)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Survival information was collected continuously every 3 months after completion of therapy and/or follow-up (range: 1-19 months).
measure: The Number of Patients With a Best Overall Response of Either a Complete Response (CR) or Partial Response (PR)
timeFrame: 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.
measure: 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).
timeFrame: First day of treatment to the end of Cycle 2, Week 1
measure: Time to Progression (TTP)
timeFrame: Time from randomization until the date of objective tumor progression was first reported (range: 11 -38 months)
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 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.
measure: Change From Baseline in Quality of Life (QoL) Assessment Using the Linear Analog Scale Assessment (LASA), Overall QoL at Cycle 2 Week 4
timeFrame: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up
measure: Change From Baseline in QoL Assessment Using LASA, Overall Mental Well Being, at Cycle 2 Week 4
timeFrame: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up
measure: Change From Baseline in QoL Assessment Using LASA, Overall Physical Well Being, at Cycle 2 Week 4
timeFrame: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up
measure: Change From Baseline in QoL Assessment Using LASA, Overall Emotional Well Being, at Cycle 2 Week 4
timeFrame: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up
measure: Change From Baseline in QoL Assessment Using LASA, Level of Social Activity, at Cycle 2 Week 4
timeFrame: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up
measure: Change From Baseline in QoL Assessment Using LASA, Overall Spiritual Well Being, at Cycle 2 Week 4
timeFrame: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up while receiving study drug
measure: Change From Baseline in QoL Assessment Using LASA, Frequency of Pain, at Cycle 2 Week 4
timeFrame: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up
measure: Change From Baseline in QoL Assessment Using LASA, Severity of Pain, Average, at Cycle 2 Week 4
timeFrame: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up while receiving study drug
measure: Change From Baseline in QoL Assessment Using LASA, Level of Fatigue, Average, at Cycle 2 Week 4
timeFrame: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up
measure: Change From Baseline in QoL Assessment Using LASA, Level of Support, Friends and Family, at Cycle 2 Week 4
timeFrame: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up
measure: Change From Baseline in QoL Assessment Using LASA, Financial Concerns, at Cycle 2 Week 4
timeFrame: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up
measure: Change From Baseline in QoL Assessment Using LASA, Legal Concerns, at Cycle 2 Week 4
timeFrame: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up
measure: Change From Baseline in Assessment of Pain Using the Brief Pain Inventory (BPI) Short Form, Worst Pain, at Cycle 2 Week 4
timeFrame: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up
measure: Change From Baseline in Assessment of Pain Using BPI Short Form, Least Pain, at Cycle 2 Week 4
timeFrame: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up
measure: Change From Baseline in Assessment of Pain Using BPI Short Form, Average Pain, at Cycle 2 Week 4
timeFrame: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up
measure: Change From Baseline in Assessment of Pain Using BPI Short Form, Pain Right Now, at Cycle 2 Week 4
timeFrame: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up
measure: Change From Baseline in Assessment of Pain Using BPI Short Form, Interference, at Cycle 2 Week 4
timeFrame: Screening, and then every 8 weeks while receiving study drug to 30-day follow-up
Other outcomes:
Locations:
city: Jonesboro
country: United States
facility: ImClone Investigational Site
state: Arkansas
city: San Francisco
country: United States
facility: ImClone Investigational Site
state: California
city: Stamford
country: United States
facility: ImClone Investigational Site
state: Connecticut
city: Miami
country: United States
facility: ImClone Investigational Site
state: Florida
city: Orlando
country: United States
facility: ImClone Investigational Site
state: Florida
city: Orlando
country: United States
facility: ImClone Investigational Site
state: Florida
city: Atlanta
country: United States
facility: ImClone Investigational Site
state: Georgia
city: Augusta
country: United States
facility: ImClone Investigational Site
state: Georgia
city: Marietta
country: United States
facility: ImClone Investigational Site
state: Georgia
city: Metairie
country: United States
facility: ImClone Investigational Site
state: Louisiana
city: Billings
country: United States
facility: ImClone Investigational Site
state: Montana
city: Concord
country: United States
facility: ImClone Investigational Site
state: North Carolina
city: Philadelphia
country: United States
facility: ImClone Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: ImClone Investigational Site
state: South Carolina
city: Arlington
country: United States
facility: ImClone Investigational Site
state: Texas
city: Dallas
country: United States
facility: ImClone Investigational Site
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: E-mail: ClinicalTrials@ ImClone.com
role: STUDY_CHAIR
References:
citation: 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.