Pilot Study of Sequential Angiogenic Blockade for the Treatment of Recurrent Mullerian Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Therapy Completion Rate
研究概览
简要总结
The goals of this study were to evaluate the efficacy and safety of sequentially blocking the angiogenesis pathway via known antiangiogenic mechanisms, first with bevacizumab and then addition of oral cyclophosphamide upon progression of cancer through bevacizumab. The drugs used in this study were chosen because of their known antiangiogenic properties, tolerability, and anti-ovarian cancer effects.
详细描述
OBJECTIVES:
Primary
- Assess the efficacy of a sequential antiangiogenic blockade regimen of bevacizumab then cyclophosphamide with bevacizumab at disease progression in patients with recurrent ovarian cancer as measured by the proportion of patients who remain on study at three months (4 cycles)
- Assess the safety profile with respect to gastrointestinal perforations
Secondary
- Assess other toxicity/ safety profile of this metronomic antiangiogenic approach
- Assess preliminary response rate and proportion of patients on study at 6 months
- Assess progression-free survival, time to progression and overall survival
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Histologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
- •Recurrent cancer and have received and failed a previous platinum-based chemotherapy regimen.
- •Up to 2 prior lines of chemotherapy in the recurrent setting (either platinum-based or non-platinum regimens). Biologic therapies count as a prior line but hormonal therapies do not count.
- •Platinum-resistant or platinum-sensitive recurrence.
- •Must be able to take oral medications and have no evidence of bowel obstruction or partial bowel obstruction
- •Measurable disease by either RECIST or Rustin criteria
- •No chemotherapy, radiation therapy, nor biologic therapy within the last three weeks prior to initiating therapy
- •ECOG score of 0 or 1
- •Life expectancy of 12 weeks or greater
- •18 years of age or older
- •Laboratory values as outlined in the protocol
- •Patients with treated limited stage basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the breast or cervix are eligible. Subjects with stage I or II cancer treated with curative intent and no evidence of recurrent disease are also eligible.
- •No evidence of preexisting hypertension. If patient has hypertension, it must be controlled medically (less than 150/90) prior to starting bevacizumab
- •Normal blood coagulation parameters
- •No prior treatment with any other antiangiogenic agents or cyclophosphamide
- •For patients who have received prior doxorubicin or pegylated doxorubicin, LVEF must be 50% or greater.
排除标准
- •Current, recent (within 4 weeks of the first study infusion), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
- •Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last five years
- •Uncontrolled diarrhea
- •Prior history of hypertensive crisis or hypertensive encephalopathy
- •NYHA Grade II or greater congestive heart failure
- •History of myocardial infarction or unstable angina within 6 months prior to Day 1
- •History of stroke or transient ischemic attack within 6 months prior to day 1
- •Known CNS disease, except for treated brain metastasis
- •Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS: Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 will be excluded.
- •Significant vascular disease within 6 months prior to day 1
- •History of hemoptysis within 1 month prior to day 1
- •Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 or anticipation of need for major surgical procedure during the course of the study
- •Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
- •History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
- •Serious, non-healing wound, active ulcer, or untreated bone fracture
- •Proteinuria as demonstrated by a UPC ratio of 1.0 or greater at screening
- •Known hypersensitivity to any component of bevacizumab
- •Pregnancy (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in subjects of child-bearing potential
研究组 & 干预措施
Bevacizumab then Cyclophosphamide with Bevacizumab
Patients were given a regimen of sequential antiangiogenic blockade and disease assessed serologically and radiologically every 2 cycles/6 weeks. Patients started with bevacizumab 15 mg/kg IV every 3 weeks until they experienced progressive disease (PD) [RECIST 1.0 or Rustin criteria] or significant toxicity. If clinically stable as assessed by their treating physician, patients then received cyclophosphamide 50 mg orally (PO) daily continuously with bevacizumab treatment. If second PD occurred, patients discontinued the combination treatment.
干预措施: Bevacizumab (Drug)
Bevacizumab then Cyclophosphamide with Bevacizumab
Patients were given a regimen of sequential antiangiogenic blockade and disease assessed serologically and radiologically every 2 cycles/6 weeks. Patients started with bevacizumab 15 mg/kg IV every 3 weeks until they experienced progressive disease (PD) [RECIST 1.0 or Rustin criteria] or significant toxicity. If clinically stable as assessed by their treating physician, patients then received cyclophosphamide 50 mg orally (PO) daily continuously with bevacizumab treatment. If second PD occurred, patients discontinued the combination treatment.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Therapy Completion Rate
时间窗: Serologic and radiologic disease assessments occurred every 2 cycles/6 weeks on treatment. Median treatment duration for this study cohort was 7.5 months (range 0.7-20.7).
The therapy completion rate is defined as the proportion of participants who completed at least 3 months/4 cycles of therapy. Participants were treated until disease progression on the combination regimen or unacceptable toxicity. Clinical response was evaluated based on RECIST 1.0 criteria for measurable disease (MD) participants and Gynecologic Cancer Intergroup (GCIG) CA-125 (Rustin) criteria for non-MD participants. Per RECIST 1.0 for target lesions, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Serologic PD is rise in CA-125 or previously normal CA125 that rises to \>/=2xULN documented, both requiring 2nd confirmation.
Grade 3-5 Gastrointestinal Perforation
时间窗: Assessed each cycle/3 weeks throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 7.5 months (range 0.7-20.7).
All grade 3-5 gastrointestinal perforation events based on CTCAEv3 as reported on case report forms.
次要结局
- Clinical Benefit Response Rate(Radiologic disease assessments occurred every 2 cycles/6 weeks on treatment. Median treatment duration for this study cohort was 7.5 months (range 0.7-20.7).)
- Progression-Free Survival (PFS)(Radiologic disease assessments occurred every 2 cycles/6 weeks on treatment and every 3 months in follow-up until PD, death or lost to follow-up. Median treatment duration was 7.5 months (range 0.7-20.7) and survival follow-up 23 months..)
- Overall Survival (OS)(Participants were followed long-term for survival every 3 months from the end of treatment until death or lost to follow-up. Median follow-up was 23 months in this study cohort.)
研究者
Ursula A. Matulonis, MD
Medical Oncologist
Dana-Farber Cancer Institute