An Open-Label, Multicenter, Randomized Phase 2 Study Evaluating the Safety and Efficacy of Ramucirumab (IMC-1121B) Drug Product or Icrucumab (IMC-18F1) in Combination With Capecitabine or Capecitabine Monotherapy, in Unresectable, Locally Advanced or Metastatic Breast Cancer Patients Previously Treated With Anthracycline and Taxane Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 153
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
An open-label, multicenter, randomized, Phase 2 trial in which participant with unresectable, locally advanced or metastatic breast cancer who have been previously treated with anthracycline and taxane therapy receive ramucirumab DP or Icrucumab (IMC-18F1) administered on an every-21-day cycle (in combination with oral capecitabine therapy; capecitabine is administered twice a day on Days 1-14 of each cycle). Approximately 150 participants will be randomized in a 1:1:1 ratio to either ramucirumab DP or Icrucumab (IMC-18F1) in combination with capecitabine (Arm A and Arm B, respectively) or capecitabine monotherapy (Arm C). Randomization will be stratified by triple-negative receptor status (estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor-2 [HER2/neu]-negative) (yes/no) and receipt of prior antiangiogenic therapy.
Treatment with the study medication(s) will continue until disease progression, the development of unacceptable toxicity, noncompliance or withdrawal of consent by the participant, or investigator decision. Capecitabine dose reductions in the setting of significant myelosuppression, hand-and-foot syndrome, or diarrhea will be required.
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 participant has histologically or cytologically confirmed breast cancer which at the time of study entry is either Stage III disease not amenable to curative therapy or Stage IV disease
- •Has measurable or nonmeasurable disease
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •Has received prior anthracycline therapy
- •Has received prior taxane therapy
- •Participants with human epidermal growth factor receptor-2 (HER2) positive disease must have progressed on or following trastuzumab
- •Participants with hormone receptor-positive disease must have progressed on or following hormone therapy
- •Has received ≤ 3 prior chemotherapy regimens in any setting (a regimen is defined as any agent[s] that has been administered for more than 1 cycle; sequential neoadjuvant/adjuvant treatment is considered 1 regimen)
- •Has completed any prior radiotherapy ≥ 4 weeks prior to randomization
- •Has completed any prior hormonal therapy ≥ 2 weeks prior to randomization
- •Has adverse events (AEs) that have resolved to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v 4.0) from all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy,or hormonal therapy
- •Has adequate hematologic, coagulation, hepatic and renal function
- •Does not have:
- •cirrhosis at a level of Child-Pugh B (or worse) or
- •cirrhosis (any degree) and a history of hepatic encephalopathy or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
- •Has urinary protein is ≤ 1+ on dipstick or routine urinalysis; if urine protein ≥ 2+, a 24-hour urine collection must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study
- •Agrees to use adequate contraception during the study period and for 12 weeks after the last dose of study medication
排除标准
- •Has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer, curatively treated cervical carcinoma in situ, or other noninvasive carcinoma or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that there has been a disease-free interval for > 3 years
- •Has a known sensitivity to capecitabine, any of its components, or other drugs formulated with polysorbate 80
- •Has a known sensitivity to 5-fluorouracil (5-FU)
- •Has a known dihydropyrimidine dehydrogenase deficiency
- •Has received prior capecitabine treatment for advanced breast cancer
- •Has received investigational therapy within 2 weeks prior to randomization
- •Has received bevacizumab within 4 weeks prior to randomization
- •Has received more than 1 prior antiangiogenic agent for breast cancer
- •Has a known sensitivity to agents of similar biologic composition as ramucirumab DP or Icrucumab (IMC-18F1), or other agents that specifically target vascular endothelial growth factor (VEGF)
- •Has an acute/subacute bowel obstruction or history of chronic diarrhea requiring ongoing medical intervention
- •Has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders
- •Has experienced a Grade ≥ 3 bleeding event within 3 months prior to randomization
- •Is receiving prophylactic or therapeutic anticoagulation with warfarin or any other oral anticoagulant
- •Has an uncontrolled intercurrent illness, including, but not limited to uncontrolled hypertension, symptomatic anemia, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorder in the opinion of the investigator
- •Has experienced any arterial thrombotic or thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident within 6 months prior to randomization
- •Has brain metastases, uncontrolled spinal cord compression, or leptomeningeal disease
- •Has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy
- •Has received a prior allogeneic organ or tissue transplantation
- •Has undergone major surgery within 4 weeks prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization
- •Has had a serious nonhealing wound, ulcer, or bone fracture within 4 weeks prior to randomization
- •Has known HIV or AIDS infection
- •Has an elective or planned major surgery to be performed during the course of the trial
- •Participant is pregnant or lactating
研究组 & 干预措施
Ramucirumab DP + Capecitabine
Cycles repeat until disease progression, the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant.
干预措施: Ramucirumab DP (Biological)
Ramucirumab DP + Capecitabine
Cycles repeat until disease progression, the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant.
干预措施: Capecitabine (Drug)
Icrucumab + Capecitabine
Cycles repeat until disease progression, the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant.
干预措施: IMC-18F1 (Biological)
Icrucumab + Capecitabine
Cycles repeat until disease progression, the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant.
干预措施: Capecitabine (Drug)
Capecitabine*
Crossover Study:
* At the discretion of the investigator, participants will be eligible to receive either ramucirumab DP or Icrucumab (IMC-18F1) in combination with capecitabine, after radiographic disease progression while on capecitabine. The investigator will decide which investigational product will be given.
Cycles repeat every 21 days until disease progression, the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant.
干预措施: Capecitabine (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 97 weeks)
PFS is defined as the time from the date of randomization until the date of objectively determined progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death from any cause, whichever is first. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 millimeter (mm) and the appearance of ≥1 new lesions was progression. Participants who did not progress, were lost to follow-up, or had missed 2 or more scheduled tumor assessments were censored at the day of their last adequate tumor assessment.
次要结局
- Percentage of Participants With Objective Response Rate (ORR)(From Date of Randomization until Disease Progression/Recurrence (Up to 97 weeks))
- Minimum Concentration (Cmin) Ramucirumab Drug Product (DP) or Icrucumab(Cycle 2,4,6,8,0,12,14,16,18,22: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion)
- Overall Survival (OS)(From Date of Randomization until Death Due to Any Cause (Up To 160 weeks))
- Number of Participants With Adverse Events (AEs)(Up To 160 Weeks)
- Area Under the Concentration Versus Time Curve From Time Zero to Infinity of Ramucirumab or Icrucumab(Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion)
- Number of Participants With Serious Adverse Events (SAEs)(Up To 160 Weeks)
- Terminal Half-life (t½) of Ramucirumab or Icrucumab(Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion)
- Clearance (Cl) of Ramucirumab or Icrucumab(Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion)
- Maximum Concentration (Cmax) Ramucirumab Drug Product (DP) or Icrucumab(Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion)
- Volume of Distribution at Steady State (Vss) of Ramucirumab or Icrucumab(Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion)
- Duration of Response(From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 97 weeks))
- Number of Participants With Anti-Ramucirumab and Anti-Icrucumab Antibodies(Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion)