Comparison of Two Preemptive Treatment Strategies of Panitumumab Mediated Skin Toxicity and Assessment of Quality of Life in Patients With Ras-wildtype Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 88
- 试验地点
- 1
- 主要终点
- Percentage of patients developing no skin toxicity ≥ grade 2
研究概览
简要总结
80 - 90 % of the patients treated with anti-EGFR antibodies (panitumumab or cetuximab) experience skin toxicity, mostly acne like skin rash.
A standardized treatment of skin rash is neither established as standard arm for clinical trials nor as guideline for the treatment of skin toxicity in clinical practice. While an improvement of QoL has been demonstrated for panitumumab and cetuximab in comparison to best supportive care the data basis for patient related outcomes regarding skin toxicity deriving from randomized trials is still small.
Recent surveys among German oncologist revealed that physicians are reluctant to use oral antibiotics as preemptive treatment . Only 19 out of 110 oncologists stated that they are thinking about using preemptive treatment in patients with acne-like skin rash.
Thus, in the present trial two main questions will be addressed:
(i) Can preemptive treatment with oral doxycycline be replaced by a sequential skin treatment strategy (i.e. local treatment with erythromycin followed by doxycycline in case of inefficacy = development of acne) without compromising treatment efficacy of skin toxicity treatment? (ii) Comparison of general and skin related QoL between both treatment arms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 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
- •Patients with wild-type RAS (KRAS and NRAS) status of metastatic colorectal cancer treatment with panitumumab according to label
- •RAS wild-type tested in
- •KRAS exon 2 (codons 12/13)
- •KRAS exon 3 (codons 59/61)
- •KRAS exon 4 (codons 117/146)
- •NRAS exon 2 (codons 12/13)
- •NRAS exon 3 (codons 59/61)
- •NRAS exon 4 (codons 117/146)
- •treatment with pre-emptive study medication shall begin the day before treatment start with panitumumab
- •Willingness to cope with biweekly quality of life questionnaires
- •Written Informed consent
- •Aged at least 18 years
- •ECOG Performance Status 0-2
- •Life expectancy of at least 12 weeks
- •Adequate haematological, hepatic, renal and metabolic function parameters:
- •Leukocytes > 3000/mm³
- •ANC ≥ 1500/mm³
- •Platelets ≥ 100,000/mm³
- •Haemoglobin > 9 g/dl
- •Serum creatinine ≤ 1.5 x ULN
- •Bilirubin ≤ 1.5 x ULN
- •GOT-GPT ≤ 2.5 x ULN (in case of liver metastases GOT / GPT ≤ 5 x ULN)
- •AP ≤ 5 x ULN
- •Magnesium, Calcium and potassium within normal ranges (may be substituted before study entry)
- •Exclusion criteria:
- •Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
- •Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment (adequate: oral contraceptives, intrauterine device or barrier method in conjunction with spermicidal jelly).
- •Serious concurrent diseases
- •On-treatment participation in a clinical study in the period 30 days prior to inclusion
- •Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrolment.
- •History of interstitial lung disease, e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.
- •History of HIV infection.
- •Other previous or concurrent malignancy (≤ 5 years prior to enrolment in study) except non-melanoma skin cancer or cervical carcinoma FIGO stage 0- 1 if the patient is continuously disease-free
- •Known allergic reactions on panitumumab, doxycycline or erythromycin
- •Previous treatment with anti-cancer agents directed against EGFR (e.g. cetuximab, panitumumab, erlotinib, gefitinib, lapatinib)
- •Skin rash existing before or due to other reasons than panitumumab treatment
- •Other dermatologic disease that may interfere with correct grading of panitumumab induced skin rash
- •Parallel treatment with anti-tumor agents other than panitumumab
排除标准
- 未提供
研究组 & 干预措施
Erythromycin
Experimental Arm (ARM A) skin- treatment: erythromycin cream 2% daily at bedtime doxycycline 100mg b.i.d.if skin toxicity CTC° ≥2 skin moisturizer daily at morning, sunscreen before going outdoors for 8 weeks
干预措施: Erythromycin (Drug)
Doxycyline
Standard Arm (ARM B) skin- treatment:doxycycline 100mg b.i.d. skin moisturizer daily at morning, sunscreen before going outdoors for 8 weeks
干预措施: Doxycycline (Drug)
结局指标
主要结局
Percentage of patients developing no skin toxicity ≥ grade 2
时间窗: 8 weeks
Percentage of patients developing no skin toxicity ≥ grade 2 at any time during their first 8-weeks of treatment with panitumumab.
次要结局
- late skin toxicity(from week 8 to 12)
- Assess Skin toxicity(8 weeks)
- Correlation between skin-related and global quality of life(8 weeks)
- Quality of life(8 weeks)
- Skin-toxicity related dose reductions of panitumumab(8 weeks)