Surgery and Intraperitoneal Hyperthermic Chemotherapy in Patients With Platinum Sensitive Recurrent Ovarian Cancer .
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 主要终点
- Progression free survival,Overall survival, post operative complications(bowel obstruction,intestinal perforation, hemathologic toxicity (granulocytopenia,thrombocytopenia,anemia),neuropathy.
研究概览
简要总结
In patient with a platinum sensitive ovarian cancer recurrence is demonstrated that the re-challenge with a compound of platinum-based, or a treatment with carboplatin in combination with paclitaxel , determines a rate of clinical response similar to the primary treatment, which is all the more important as the longer the time to progression from the primary therapy.In the clinical setting there are many studies that have shown activity of oxaliplatin and docetaxel in patients with advanced ovarian cancer. Two recent studies have shown clinical efficacy of the combination carboplatin / docetaxel in the first line oxaliplatin / paclitaxel to recurrence of disease, confirming the data already obtained from studies of activity in a single agent.In surgery it has been demonstrated in a meta-analysis including approximately 7000 patients in advanced stages of disease, that the extent of cytoreduction is the most powerful determinant of survival.The role of secondary surgical cytoreduction in case of recurrent disease has yet to be determined because of the lack of prospective randomized clinical studies that may highlight the superiority of such aggressive treatment.The combination of aggressive cytoreductive surgery and hyperthermic intraperitoneal intraoperative chemotherapy (CHIP) used in recent clinical studies showed a prolonged time to progression and disease-free survival in patients with ovarian cancer. However, these studies were conducted on groups of patients with very different among themselves and with other drugs, it is difficult to draw definitive conclusions.Given the activities of oxaliplatin and docetaxel and their non-cross-resistance we designed a Phase 2 clinical trial on treatment of patients with recurrent ovarian cancer, platinum-sensitive, treated with surgical cytoreduction with hyperthermic oxaliplatin-based intraoperative intraperitoneal chemotherapy and following consolidation treatment with oxaliplatin and docetaxel systemically every 21 days.
详细描述
Among the malignancies of the female genital tract, ovarian cancer is the second most common cancer after the endometrial tumor, but the more lethal, representing the fifth leading cause of death among women in industrialized countries. For the most part, these are epithelial tumors (>70%), who begin with vague gastrointestinal symptoms, general malaise, abdominal bloating, weight loss and fatigue. Because of the non-specificity oh the symptoms and the often late presentation, about 70% of the diagnosis is made at an advanced stage of disease (IIIC). In the last two decades only a modest improvement in survival was achieved. Moreover, even after optimal cytoreduction followed by adjuvant chemotherapy based on platinum and taxane, which is currently the standard for this type of disease, most patients with stage III disease developed a recurrence.
Rational of HIPEC in recurrent ovarian cancer: the cytoreduction. Contrary to what happens in the primary disease is not yet clear what is the standard treatment in recurrent epithelial ovarian cancer (EOC).
Patients who experience a recurrence within 6 months from the end of the first-line chemotherapy are considered platinum-resistant and have applied for a salvage treatment with second line drugs with low response rates and poor survival. Patients who recur after 6 months are considered platinum-sensitive and, therefore, subject to a new chemotherapy treatment with a platinum compound possibly in combination with paclitaxel (re-challenge). In these patients it is possible to achieve a clinical response rate similar to the primary treatment, with median survival reported between 12 and 24 months. Recently surgery affirmed a major role not only in the primary treatment but also in recurrent chemo-sensitive ovarian cancer. A meta-analysis of 2019 patients has shown that obtain an optimal secondary cytoreduction independently correlates with survival (OS) after recurrence. However, a recent Cochrane, showed that, from the studies available nowadays, is not possible to substantiate a difference in prognosis between the exclusive chemotherapy treatment and the association of surgery with adjuvant chemotherapy.
The results of the multicenter trial DESKTOP I show that, even in the presence of peritoneal carcinomatosis, the 2-year survival improves if an optimal cytoreduction is obtained.
Rational of HIPEC in recurrent ovarian cancer: intraperitoneal chemotherapy Many patients who undergo optimal cytoreduction may benefit from adjuvant chemotherapy administered intraperitoneally (IP). Several randomized trials have demonstrated improved survival associated with IP platinum-based chemotherapy as first-line adjuvant therapy after optimal cytoreduction, although it is still unclear which patients might benefit most, or what would be the best drug , its dose or the right number of cycles. The adjuvant IP therapy, however, seems to have more side effects than intravenous therapy (IV) and consequently a worsening of the quality of life (QOL).
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 65 Years(Adult, Older Adult)
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age over 18 and under 70 years
- •Patients affected by a first recurrence of ovarian cancer with measurable lesions or not, but evaluable (upwards of Ca125 for 2 consecutive assessments).
- •ECOG-performance status ≤ 2
- •Ovarian cancer limited to the abdominal cavity with or without extraperitoneal spread considered resectable at intraoperative evaluation
- •Evidence of tumor recurrence diagnosed after 6 months from primary treatment
- •Previous-based chemotherapy of carboplatin and taxanes
- •Positive Peritoneal Washing in the presence of other abdominal disease surgically resectable
- •Adequate respiratory, hepatic, cardiac, kidney and bone marrow function (absolute neutrophil count > 1500/mm3, platelets > 150,000/μl, creatinine clearance > 60 mL/min according to Cockroft formula)
- •Patient-compliant and psychologically able to follow the trial procedures
排除标准
- •Non-epithelial ovarian cancer or borderline ovarian tumor
- •Pregnancy or breastfeeding
- •Patients affected by major depressive disorder even in treatment or minor mood disorders
- •Patients with severe impairment of respiratory, hepatic or renal function
- •Patients with cardiac, neurological or metabolic uncontrolled pharmacologically disease
- •Patients with active infection or other neoplastic disease in progress
- •Patients with bowel obstruction
- •Inadequate bone marrow, liver, kidney function
- •No clear-peritoneal disease at surgical exploration
- •Patients with ascites > 500 ml (the TAC)
- •Patients on maintenance therapy with Antiangiogenic drugs
- •Patients with secondary or tertiary recurrence, or already submitted to HIPEC
- •Patients who have already made the second or third line chemotherapy.
结局指标
主要结局
Progression free survival,Overall survival, post operative complications(bowel obstruction,intestinal perforation, hemathologic toxicity (granulocytopenia,thrombocytopenia,anemia),neuropathy.
时间窗: 6-32 months
Efficacy and tolerability of the treatment with intraoperative intraperitoneal hyperthermic chemotherapy with oxaliplatin after optimal debulking surgery in patients with platinum-sensitive recurrent ovarian cancer followed by systemic chemotherapy with docetaxel 75mg / m g1 and oxaliplatin 100 mg / m² every 21 days x g1 for six consecutive cycles.
次要结局
未报告次要终点
研究者
Prof. Giovanni Scambia
Clinical Professor
Catholic University of the Sacred Heart
