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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 ≤
- •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.
排除标准
- •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
研究组 & 干预措施
cetuximab + bevacizumab + gemcitabine
Cetuximab 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.
干预措施: cetuximab (Biological)
cetuximab + bevacizumab + gemcitabine
Cetuximab 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.
干预措施: bevacizumab (Biological)
cetuximab + bevacizumab + gemcitabine
Cetuximab 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.
干预措施: gemcitabine (Drug)
cetuximab + bevacizumab
Cetuximab 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.
干预措施: cetuximab (Biological)
cetuximab + bevacizumab
Cetuximab 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.
干预措施: bevacizumab (Biological)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: Time from randomization to disease progression or death from any cause (Range: 0 -10 months)
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.
次要结局
- Overall Survival (OS)(Survival information was collected continuously every 3 months after completion of therapy and/or follow-up (range: 1-19 months).)
- The Number of Patients With a Best Overall Response of Either a Complete Response (CR) or Partial Response (PR)(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.)
- 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).(First day of treatment to the end of Cycle 2, Week 1)
- Time to Progression (TTP)(Time from randomization until the date of objective tumor progression was first reported (range: 11 -38 months))
- Change From Baseline in QoL Assessment Using LASA, Severity of Pain, Average, at Cycle 2 Week 4(Screening, and then every 8 weeks while receiving study drug to 30-day follow-up while receiving study drug)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(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.)
- Change From Baseline in Quality of Life (QoL) Assessment Using the Linear Analog Scale Assessment (LASA), Overall QoL at Cycle 2 Week 4(Screening, and then every 8 weeks while receiving study drug to 30-day follow-up)
- Change From Baseline in QoL Assessment Using LASA, Overall Mental Well Being, at Cycle 2 Week 4(Screening, and then every 8 weeks while receiving study drug to 30-day follow-up)
- Change From Baseline in QoL Assessment Using LASA, Overall Physical Well Being, at Cycle 2 Week 4(Screening, and then every 8 weeks while receiving study drug to 30-day follow-up)
- Change From Baseline in QoL Assessment Using LASA, Overall Emotional Well Being, at Cycle 2 Week 4(Screening, and then every 8 weeks while receiving study drug to 30-day follow-up)
- Change From Baseline in QoL Assessment Using LASA, Level of Social Activity, at Cycle 2 Week 4(Screening, and then every 8 weeks while receiving study drug to 30-day follow-up)
- Change From Baseline in QoL Assessment Using LASA, Overall Spiritual Well Being, at Cycle 2 Week 4(Screening, and then every 8 weeks while receiving study drug to 30-day follow-up while receiving study drug)
- Change From Baseline in QoL Assessment Using LASA, Frequency of Pain, at Cycle 2 Week 4(Screening, and then every 8 weeks while receiving study drug to 30-day follow-up)
- Change From Baseline in QoL Assessment Using LASA, Level of Fatigue, Average, at Cycle 2 Week 4(Screening, and then every 8 weeks while receiving study drug to 30-day follow-up)
- Change From Baseline in QoL Assessment Using LASA, Level of Support, Friends and Family, at Cycle 2 Week 4(Screening, and then every 8 weeks while receiving study drug to 30-day follow-up)
- Change From Baseline in QoL Assessment Using LASA, Financial Concerns, at Cycle 2 Week 4(Screening, and then every 8 weeks while receiving study drug to 30-day follow-up)
- Change From Baseline in QoL Assessment Using LASA, Legal Concerns, at Cycle 2 Week 4(Screening, and then every 8 weeks while receiving study drug to 30-day follow-up)
- Change From Baseline in Assessment of Pain Using the Brief Pain Inventory (BPI) Short Form, Worst Pain, at Cycle 2 Week 4(Screening, and then every 8 weeks while receiving study drug to 30-day follow-up)
- Change From Baseline in Assessment of Pain Using BPI Short Form, Least Pain, at Cycle 2 Week 4(Screening, and then every 8 weeks while receiving study drug to 30-day follow-up)
- Change From Baseline in Assessment of Pain Using BPI Short Form, Average Pain, at Cycle 2 Week 4(Screening, and then every 8 weeks while receiving study drug to 30-day follow-up)
- Change From Baseline in Assessment of Pain Using BPI Short Form, Pain Right Now, at Cycle 2 Week 4(Screening, and then every 8 weeks while receiving study drug to 30-day follow-up)
- Change From Baseline in Assessment of Pain Using BPI Short Form, Interference, at Cycle 2 Week 4(Screening, and then every 8 weeks while receiving study drug to 30-day follow-up)