A Phase I Trial of Sequential Ipilimumab After Chemoradiation for the Primary Treatment of Patients With Locally Advanced Cervical Cancer Stages IB2/IIA With Positive Para-Aortic Lymph Nodes Only and Stage IIB/IIIB/IVA With Positive Lymph Nodes
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 16
- 主要终点
- DLTs occurring during adjuvant ipilimumab in the dose escalation phase
研究概览
简要总结
This phase I trial studies the side effects and best dose of ipilimumab when given after chemoradiation therapy in treating patients with stages IB2-IIB or IIIB-IVA cervical cancer. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Monoclonal antibodies, such as ipilimumab, may find tumor cells and help carry tumor-killing substances to them. Giving ipilimumab together with chemoradiation therapy may be a better way treat cervical cancer.
详细描述
PRIMARY OBJECTIVES:
I. To estimate the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of adjuvant ipilimumab following concurrent weekly cisplatin and extended field radiation in women with newly diagnosed locally advanced cervical cancer stage IB2/ IIA with-positive para-aortic lymph nodes only and stage IIB/IIIB/IVA with positive lymph nodes.
II. To determine the feasibility of the treatment regimen over the four cycles of adjuvant ipilimumab once the MTD is estimated.
III. To assess the toxicities of the treatment regimen per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
SECONDARY OBJECTIVES:
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 with histologically confirmed advanced cervical cancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma): International Federation of Gynecology and Obstetrics (FIGO) clinical stages IB2/IIA with positive para-aortic lymph nodes or FIGO clinical stages IIB/IIIB/IVA with positive pelvic and/or para-aortic lymph nodes; nodal status will be confirmed by PET/CT scan, fine needle biopsy, extra peritoneal biopsy, laparoscopic biopsy or lymphadenectomy
- •Patients must have a Gynecologic Oncology Group (GOG) performance status of 0-1
- •Absolute neutrophil count (ANC) >= 1,500/mcl
- •Platelets >= 100,000/mcl
- •Creatinine =< institutional upper limit normal (ULN); note: if creatinine > ULN, creatinine clearance must be > 50 mL/min
- •Bilirubin =< 1.5 x ULN
- •Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
- •Alkaline phosphatase =< 2.5 x ULN
- •Neuropathy (sensory and motor) =< grade 1
- •Patients with ureteral obstruction (i.e., hydronephrosis identified on CT imaging) must undergo stent or nephrostomy tube placement prior to study entry
- •Patients must meet the pre-entry requirements specified
- •Patients must have signed an approved informed consent and authorization permitting the release of personal health information
- •Patients of child-bearing potential must have a negative serum pregnancy test prior to study entry (within 72 hours prior to initiation of study treatment) and be practicing an effective form of contraception; women should not breast-feed while on this study
- •Patients must not be receiving any other investigational agent
- •Patients should have an audiogram at baseline, and patients with pre-existing hearing loss or hearing loss during treatment should be assessed frequently during cisplatin therapy
排除标准
- •Patients who have received previous pelvic or abdominal radiation, cytotoxic chemotherapy, or previous therapy of any kind for this malignancy or any pelvic or abdominal radiation for any prior malignancy
- •Patients with active infection
- •Patients who have circumstances that will not permit completion of this study or the required follow-up
- •Patients with renal abnormalities, such as pelvic kidney, horseshoe kidney, or renal transplantation, that would require modification of radiation fields
- •Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment prevents full delivery of this protocol therapy
- •Patients who have undergone major surgery, excluding diagnostic biopsy, within 30 days (to allow for full recovery) prior to registration
- •Patients who have a significant history of cardiac disease, i.e., uncontrolled hypertension, unstable angina, congestive heart failure, or uncontrolled arrhythmias within 6 months of registration
- •Patients with a history of prior treatment with ipilimumab, anti-programmed cell death (PD) 1 antibody, cluster of differentiation (CD)137 agonist or other immune activating therapy such as anti-CD 40 antibody
- •Patients who are receiving any other investigational agents
- •Autoimmune disease: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre syndrome and myasthenia gravis, multiple sclerosis)
- •Patients with known immune impairment who may be unable to respond to anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA 4) antibody
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition ipilimumab or other agents used in study
- •Patients with chronic human immunodeficiency virus (HIV), hepatitis B or hepatitis C infections should be excluded
研究组 & 干预措施
Treatment (cisplatin, radiation therapy, and ipilimumab)
Patients receive cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, and 36, undergo extended beam radiation therapy 5 days a week for 6 weeks, and then undergo intracavitary brachytherapy for approximately 2 weeks. Within 2 weeks, patients receive ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks.
干预措施: Cisplatin (Drug)
Treatment (cisplatin, radiation therapy, and ipilimumab)
Patients receive cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, and 36, undergo extended beam radiation therapy 5 days a week for 6 weeks, and then undergo intracavitary brachytherapy for approximately 2 weeks. Within 2 weeks, patients receive ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks.
干预措施: External Beam Radiation Therapy (Radiation)
Treatment (cisplatin, radiation therapy, and ipilimumab)
Patients receive cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, and 36, undergo extended beam radiation therapy 5 days a week for 6 weeks, and then undergo intracavitary brachytherapy for approximately 2 weeks. Within 2 weeks, patients receive ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks.
干预措施: Internal Radiation Therapy (Radiation)
Treatment (cisplatin, radiation therapy, and ipilimumab)
Patients receive cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, and 36, undergo extended beam radiation therapy 5 days a week for 6 weeks, and then undergo intracavitary brachytherapy for approximately 2 weeks. Within 2 weeks, patients receive ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks.
干预措施: Ipilimumab (Biological)
Treatment (cisplatin, radiation therapy, and ipilimumab)
Patients receive cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, and 36, undergo extended beam radiation therapy 5 days a week for 6 weeks, and then undergo intracavitary brachytherapy for approximately 2 weeks. Within 2 weeks, patients receive ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks.
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
DLTs occurring during adjuvant ipilimumab in the dose escalation phase
时间窗: During first 2 courses of treatment
Toxicities as assessed by CTCAE version 4
时间窗: Up to 2 years post-treatment
DLTs occurring in the feasibility phase
时间窗: Over 4 courses of treatment
次要结局
- Response rate in patients enrolled with measurable disease assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1(Up to 2 years post-treatment)
- Overall survival(From time of study entry to time of death or the date the patient was last confirmed to be alive, assessed up to 1 year post-treatment)
- Chronic toxicities experienced within one year of completion of therapy(Up to 1 year post-treatment)
- Location of recurrence (loco-regional versus distant)(Up to 1 year post-treatment)
- Progression-free survival (PFS)(From time of study entry to time of progression or death, whichever occurs first, assessed up to 1 year post-treatment)