Multi-institutional Phase I/II Study: Neoadjuvant Chemoradiation With 5-FU (or Capecitabine) and Oxaliplatin Combined With Deep Regional Hyperthermia in Locally Advanced or Recurrent Rectal Cancer
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 59
- 试验地点
- 6
- 主要终点
- Feasibility rate (i.e. rate of patients not experiencing dose-limiting toxicity [DLT])
研究概览
简要总结
This trial examines the feasibility, effectiveness and safety of a combination of radiotherapy (over a period of five weeks) and chemotherapy (with 5-FU or Capecitabine and Oxaliplatin) and 10 fractions of deep regional hyperthermia in patients with primary locally advanced or locally recurrent rectal cancer. Previous pelvic irradiation in case of a local recurrence is not excluded from the trial. The treatment protocol aims on a preoperatively improved tumor regression allowing less aggressive surgery in primary locally advanced rectal cancer and a higher rate of curative resections in heavily pretreated locally recurrent rectal cancers.
Primary endpoint of the trial is the feasibility rate of a multimodal regimen consisting of radiochemotherapy and hyperthermia. Secondary endpoints are local control, survival rates, and toxicity. It is planned to include a total number of 59 patients over a period of 2.5 years.
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
- •Age ≥ 18 years
- •Histologically confirmed, locally advanced or recurrent (any recurrence of tumor within the lesser pelvis; resectable or non-resectable) adenocarcinoma of the rectum (UICC stage IIB-IV); distant oligo-metastases may be present.
- •ECOG-performance status < 2
- •Sufficient bone marrow function:
- •WBC > 3,5 x 10^9/l
- •Neutrophil granulocytes > 1,5 x 10^9/l
- •Platelets > 100 x 10^9/l
- •Hemoglobin > 10 g/dl
- •Sufficient liver function: Bilirubin < 2,0 mg%, SGOT, SGPT, alkaline phosphatase, gGT less than 3 times upper limit of normal
- •Serum creatinine < 1,5 mg%, glomerular filtration rate (or comparable test) > 50 ml/min
- •Signed study-specific consent form prior to therapy
- •Fertile patients must use effective contraception during and for 6 months after study treatment
- •Considered fit for oxaliplatin and 5-FU-containing combination chemotherapy
排除标准
- •Pelvic radiotherapy during the last 12 months
- •Pregnant or lactating/nursing women
- •Drug addiction
- •On-treatment participation on other trials
- •Active intractable or uncontrollable infection
- •Prior or concurrent malignancy (≤ 5 years prior to enrolment in study) except rectal cancer or non-melanoma skin cancer or cervical carcinoma FIGO stage 0-1 if the patient is continuously disease-free
- •Chronic diarrhea (> NCI CTC-Grad 1)
- •Chronic inflammatory disease of the intestine
- •Collagen vascular disease
- •The presence of congenital diseases with increased radiation sensitivity, for example teleangiectatic ataxia, or similar
- •Pre-existing uncontrolled cardiac disease, signs of cardiac failure, or rhythm disturbances requiring therapy
- •Myocardial infarction within the past 12 months
- •Congestive heart failure
- •Complete bundle branch block
- •New York Heart Association (NYHA) class III or IV heart disease
- •Known allergic reactions on study medication
- •Cardiac pacemaker
- •Disease that would preclude chemoradiation or deep regional hyperthermia
- •Any metal implants (with exception of non-clustered marker clips)
- •Psychological, familial, sociological, or geographical condition that would preclude study compliance
- •Patients deemed technically unsatisfactory for deep regional hyperthermia
- •Cardiac symptoms (> NCI CTCAE Grade 1) due to pretreatment with fluoropyrimidines
- •Neurological symptoms (> NCI CTCAE Grade 1) due to pretreatment with oxaliplatin
- •Rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
- •Oral anticoagulation
研究组 & 干预措施
HyRec
Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin
干预措施: Radiotherapy (Radiation)
HyRec
Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin
干预措施: Hyperthermia (Procedure)
HyRec
Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin
干预措施: 5-Fluorouracil (Drug)
HyRec
Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin
干预措施: Capecitabine (Drug)
HyRec
Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Feasibility rate (i.e. rate of patients not experiencing dose-limiting toxicity [DLT])
时间窗: Participants will be followed for the duration of therapy and for 6 weeks after the last study treatment dose (approximately 11 to 12 weeks)
Number of hyperthermia applications by patient
时间窗: Duration of therapy (approximately 5 to 6 weeks)
次要结局
- Local progression-free survival(Participants will be followed for up to 5 years after the end of therapy (Follow up period))
- Distant metastasis-free survival(Participants will be followed for up to 5 years after the end of therapy (Follow up period))
- Response rate(Participants will be followed for up to 5 years after the end of therapy (Follow up period))
- Rate of R0-resections(Only of participants who are considered as resectable receive surgery in curative intention 4-6 weeks after completion of chemoradiation (results app. after 10 to 12 weeks after start of therapy))
- Overall survival(Participants will be followed for up to 5 years after the end of therapy (Follow up period))
- Rate of acute and late toxicity(Participants will be followed for up to 5 years after the end of therapy (Follow up period))