A Phase II Evaluation of AMG 102 (Rilotumumab) (NSC #750009) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 56
- 主要终点
- Proportion of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.1
研究概览
简要总结
This phase II trial studies how well rilotumumab works in treating patients with ovarian epithelial, fallopian tube, or primary peritoneal cancer that has failed to respond to other therapies (persistent) or has returned after a period of improvement (recurrent). Rilotumumab is a type of drug called a monoclonal antibody, and may interfere with the ability of tumor cells to grow and spread by targeting certain cells and blocking them from working.
详细描述
PRIMARY OBJECTIVES:
I. To estimate the proportion of patients who survive progression-free for at least 6 months and the proportion of patients who have objective tumor response (complete or partial) in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
SECONDARY OBJECTIVES:
I. To determine the frequency and severity of adverse events associated with treatment with AMG 102 (rilotumumab) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
II. To determine the duration of progression-free survival (PFS) and overall survival (OS).
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma; histologic confirmation of the original primary tumor is required via the pathology report
- •All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
- •Patient must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
- •Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG Phase III protocol for the same patient population
- •Patients who have received one prior regimen must have a GOG performance status of 0, 1, or 2
- •Patients who have received two prior regimens must have a GOG performance status of 0 or 1
- •Recovery from effects of recent surgery, radiotherapy, or chemotherapy
- •Major surgical procedures must have taken place > 30 days before enrollment; minor surgical procedures must have taken place > 14 days before enrollment; central venous catheter placement is allowed at any time prior to enrollment provided the patient has recovered and any surgical would has healed
- •Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infections [UTI])
- •Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration
- •Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued at least three weeks prior to registration
- •Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, high-dose therapy, consolidation, non-cytotoxic agents or extended therapy administered after surgical or non-surgical assessment
- •Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease according to the following definition:
- •Cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa
- •Note: Patients on this non-cytotoxic study are allowed to have received prior cytotoxic chemotherapy for management of recurrent or persistent disease, as defined above; however, patients are encouraged to enroll on second-line non-cytotoxic studies prior to receiving additional cytotoxic therapy
- •Patients who have received only one prior cytotoxic regimen (platinum-based regimen for management of primary disease), must have a platinum-free interval of less than 12 months, or have progressed during platinum-based therapy, or have persistent disease after a platinum-based therapy
- •Patients must NOT have received any non-cytotoxic therapy for management of recurrent or persistent disease; patients are allowed to receive, but are not required to receive, biologic (non-cytotoxic) therapy as part of their primary treatment regimen
- •Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl
- •Platelets greater than or equal to 100,000/mcl
- •Hemoglobin >= 9 g/dL
- •Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)
- •Bilirubin less than or equal to 1.5 x ULN
- •Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) less than or equal to 3 x ULN
- •Alkaline phosphatase less than or equal to 2.5 x ULN
- •PTT (partial thromboplastin time) =< 1.5 x ULN
- •International normalized ratio (INR) =< 1.5 x ULN
- •Neuropathy (sensory and motor) less than or equal to CTCAE grade 1
- •Proteinuria: =< 1+ (urinalysis) or < 1 g/24 hrs (24 hour urine collection)
- •Patients must have signed an approved informed consent and authorization permitting release of personal health information
- •Patients must meet pre-entry requirements
- •Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing an effective form of contraception
排除标准
- •Patients who have had previous treatment with AMG 102 (rilotumumab) or other hepatocyte growth factor (HGF)/MET proto-oncogene, receptor tyrosine kinase (c-met) pathway inhibitors
- •Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies as noted, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
- •Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
- •Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
- •Patients with a past history of primary endometrial cancer are excluded unless all of the following conditions are met: stage not greater than I-B; no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other International Federation of Gynecology and Obstetrics (FIGO) grade 3 lesions
- •Patients with an active bleeding diathesis or on concurrent or prior (within 7 days of enrollment) therapeutic anti-coagulation therapy with warfarin, heparin, or low molecular weight heparin; the use of low-dose warfarin (=< 2 mg orally [PO] daily) for prophylaxis against central venous catheter thrombosis is allowed
- •Patients with serious intercurrent infections or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by this treatment
- •Patients who are pregnant or breastfeeding
- •Patients with psychiatric or other conditions rendering them incapable of participating in informed consent or the requirements of this protocol
- •Patients with a serious or non-healing wound
- •Patients with peripheral edema or lymphedema > grade 2
- •Patients with known positive human immunodeficiency virus (HIV) or hepatitis C or chronic or active hepatitis B
- •Patients with thromboembolic event or ischemic event within the past 12 months, such as deep venous thrombosis, pulmonary embolism, transient ischemic attack, cerebral infarction, or myocardial infarction
研究组 & 干预措施
Treatment (rilotumumab)
Patients receive rilotumumab IV over 30-60 minutes on days 1 and 14. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Tumor tissue and blood samples may be collected periodically for further laboratory analysis.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (rilotumumab)
Patients receive rilotumumab IV over 30-60 minutes on days 1 and 14. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Tumor tissue and blood samples may be collected periodically for further laboratory analysis.
干预措施: Rilotumumab (Biological)
结局指标
主要结局
Proportion of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.1
时间窗: CT scan or MRI if used to follow lesion for measurable disease every other cycle during treatment then every 3 months thereafter until disease progression is confirmed; also repeat at any time if clinically indicated up to 5 years.
Complete and Partial Tumor Response by RECIST 1.1. RECIST 1.1 defines complete response as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm and the disappearance of all non-target lesions and normalization of tumor marker level. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.
Progression-free Survival > 6 Months Using RECIST 1.0
时间窗: CT scan or MRI if used to follow lesion for measurable disease every other cycle during treatment then every 3 months thereafter until disease progression is confirmed; up to 6 months.
Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression was based on RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.
次要结局
- Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 4.0(Assessed every cycle while on treatment, 30 days after the last cycle of treatment)
- Duration of Overall Survival (OS)(Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.)
- Duration of Progression-free Survival (PFS)(CT scan or MRI if used to follow lesion for measurable disease every other cycle during treatment then every 3 months thereafter until disease progression is confirmed; also repeat at any time if clinically indicated up to 5 years.)