A Randomized Phase II/III Trial Comparing Carboplatin-Ifosfamide (IC)-Chemotherapy Vs. IC-Chemotherapy Combined With Extreme Whole Body Hyperthermia In Patients With Recurrence Of Epithelial Ovarian Carcinoma: DOLPHIN-1-STUDY
试验速览
- 阶段
- 2 期
- 入组人数
- 241
- 试验地点
- 7
- 主要终点
- Time to progressive disease
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Hyperthermia therapy kills tumor cells by heating them to several degrees above body temperature. Combining hyperthermia with chemotherapy may kill more tumor cells. It is not yet known if chemotherapy is more effective with or without whole-body hyperthermia therapy in treating gynecologic cancer.
PURPOSE: Randomized phase II/III trial to compare the effectiveness of chemotherapy with or without whole-body hyperthermia in treating patients who have recurrent ovarian epithelial, fallopian tube, or peritoneal cancer.
详细描述
OBJECTIVES:
- Compare the time to progressive disease in patients with recurrent ovarian epithelial, fallopian tube, or extraovarian peritoneal cancer treated with carboplatin and ifosfamide with or without whole body hyperthermia.
- Compare the response rate, duration of response, and survival time of patients treated with these regimens.
- Compare the effect on the presence of disseminated tumor cells in bone marrow in patients treated with these regimens.
- Compare the toxicity of these regimens in these patients.
- Assess quality of life of patients treated with these regimens.
OUTLINE: This is a phase II safety and efficacy study followed by a phase III randomized, open-label, multicenter study.
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Phase II: Patients receive ifosfamide IV over 1 hour and carboplatin IV over 20 minutes on day 1. Patients also undergo whole body hyperthermia for at least 1 hour on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
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Phase III (after successful treatment of 15 patients in phase II): Patients are stratified according to disease-free interval (6-12 months vs more than 12 months), measurable disease (bidimensionally measurable vs measurable by other clinical means), and disease recurrence (first recurrence vs second or greater recurrence). Patients are randomized to 1 of 2 treatment arms.
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Arm I: Patients receive ifosfamide, carboplatin, and whole body hyperthermia as in phase II.
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Arm II: Patients receive ifosfamide and carboplatin as in arm I.
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In both arms, treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed ovarian epithelial, fallopian tube, or extraovarian peritoneal cancer
- •Recurrent disease (any FIGO stage)
- •Not amenable to curative surgery or radiotherapy alone
- •Failed prior primary platinum-based therapy at least 6 months after therapy discontinuation
- •Measurable lesion by CT scan, MRI, chest x-ray, or sonography
- •Physical examination allowed for documenting lymph node and skin metastases
- •Physical gynecological examination allowed for well-defined palpable tumor lesions
- •Increase in CA 125 without any measurable tumor is not acceptable as indication of recurrence
- •No CNS metastases
- •No tumor of borderline malignancy
- •PATIENT CHARACTERISTICS:
- •Performance status
- •Life expectancy
- •At least 24 weeks
- •Hematopoietic
- •Neutrophil count at least 1,500/mm3
- •Platelet count at least 100,000/mm3
- •Not specified
- •Creatinine clearance at least 60 mL/min
- •No chronic or acute renal failure
- •Cardiovascular
- •Cardiovascular function sufficient for hyperthermia treatment by stress-ECG
- •No cardiomyopathy with impaired ventricular function
- •No New York Heart Association class III or IV heart disease
- •No cardiac arrhythmias influencing LVEF and requiring medication
- •No myocardial infarction or angina pectoris within the past 6 months
- •No uncontrolled arterial hypertension
- •Pulmonary function sufficient for hyperthermia treatment by pulmonary function tests
- •No untreated endocrinological disease (e.g., hyperthyroidism or diabetes mellitus)
- •No other primary malignancy except carcinoma in situ of the cervix or adequately treated basal cell skin cancer
- •No contraindication against hyperthermia treatment (e.g., photodermatosis, history of malignant hyperthermia, or claustrophobia)
- •No hypersensitivity to carboplatin, ifosfamide, or any other study medication
- •Not pregnant or nursing
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •Not specified
- •Chemotherapy
- •See Disease Characteristics
- •No concurrent cytotoxic or other antineoplastic therapy
- •Endocrine therapy
- •Concurrent hormone replacement therapy allowed
- •Concurrent steroid antiemetics allowed
- •Radiotherapy
- •See Disease Characteristics
- •At least 1 year since prior radiotherapy (tumoricidal dose) of the pelvis
- •Concurrent palliative local radiotherapy for painful (nonprogressive) existing lesion is allowed if other measurable sites are present
- •No concurrent radiotherapy to a second existing lesion
- •See Disease Characteristics
- •No prior form of hyperthermic therapy
- 另有 6 项未显示
排除标准
- 未提供
结局指标
主要结局
Time to progressive disease
Response rate
Duration of response
Survival time
Effects on the presence of disseminated tumor cells in bone marrow
Toxicity
Quality of life
次要结局
未报告次要终点