PROVE A Randomized Phase II Trial of Standard Carboplatin-based Chemotherapy With or Without Panitumumab in Platinum-sensitive Recurrent Ovarian Cancer
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 140
- 试验地点
- 18
- 主要终点
- Progression-free survival (PFS) rate after 12 months.
研究概览
简要总结
The purpose of this trial is to estimate the therapeutic efficacy of the experimental targeted regimen including the EGFR antibody panitumumab (in combination with carboplatin and either pegylated liposomal doxorubicin or gemcitabine) in relation to the respective standard combination in patients with a KRAS wildtype with platinum-sensitive recurrent ovarian cancer. It is expected that the progression free survival rate at 12 months is improved by the targeted regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Female patients with pretreated epithelial ovarian cancer, primary peritoneal carcinomatosis or fallopian tube cancer with histological confirmation of the tumor
- •Wild-type k-ras status
- •Patients must have pretreated platinum-sensitive ovarian cancer with recurrence more than 6 months after completion of a platinum-containing regimen
- •Presence of at least one measurable or non-measurable disease (e.g. malignant ascites) following RECIST criteria by radiologic evaluation OR histological confirmation of recurrence by biopsy. The presence of non-measurable lesions only requires in addition a 2-fold increase of CA-125 elevation above normal lab value (confirmed by two measurements).
- •No more than 2 prior treatment regimens for these epithelial cancers
- •Age > 18 years.
- •ECOG Performance Status of 0 or 1
- •Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
- •Hemoglobin > 9.0 g/dl
- •Leukocyte count >3.000/mm3 ; absolute neutrophil count (ANC) >1.500/mm3
- •Platelet count ≥ 100.000/μl
- •Total bilirubin < 1,0 times the upper limit of normal
- •ALT and AST < 2,5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer)
- •Alkaline phosphatase < 4 x ULN
- •PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.]
- •Serum creatinine < 1.5 x upper limit of normal and creatinine clearance > 50 ml/min.
- •Magnesium ≥ lower limit of normal; calcium ≥ lower limit of normal
- •Signed and dated informed consent before the start of specific protocol procedures.
排除标准
- •Clinically significant cardiovascular disease (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 or chronic hepatitis B or C
- •Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
- •Pre-existing neuropathy > grade 1 (NCI CTCAE), except for loss of tendon reflex
- •Prior radiological or clinical evidence of CNS metastases including previously treated, resected, or asymptomatic brain lesions or leptomeningeal involvement by head CT scan or MRI
- •Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
- •History of organ allograft
- •Patients with evidence or history of bleeding diathesis
- •Patients undergoing renal dialysis
- •Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry.
- •Patients in a closed institution according to an authority or court decision
- •Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
- •Excluded therapies and medications, previous and concomitant:
- •Anticancer chemotherapy within 4 weeks prior to study entry.
- •Prior anti-EGFR therapy
- •Radiotherapy during study or within 4 weeks of start of study drug. (Palliative radiotherapy of non-target lesions will be allowed) and prior radiotherapy of > 25% of the bone marrow
- •Major surgery within 4 weeks of start of study
- •Autologous bone marrow transplant or stem cell rescue within 12 months of study
- •Investigational drug therapy outside of this trial during or within 4 weeks of study entry
- •Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
研究组 & 干预措施
Experimental arm (A):
Caelyx 30 mg/m² d1 Carboplatin AUC 5 d1 Panitumumab 6 mg/kg/KG d1 + 15 q4w until progressive disease or for a max. of 6 cycles
OR
Gemcitabine 1000 mg/m² d1 + 8 Carboplatin AUC 4 d1 Panitumumab 9 mg/kg/KG d1 q3w until progressive disease or for a max. of 6 cycles
The backbone chemotherapy (Caelyx or Gemcitabine-based) is specified by the investigator before randomization of a patient.
干预措施: Panitumumab (Drug)
Experimental arm (A):
Caelyx 30 mg/m² d1 Carboplatin AUC 5 d1 Panitumumab 6 mg/kg/KG d1 + 15 q4w until progressive disease or for a max. of 6 cycles
OR
Gemcitabine 1000 mg/m² d1 + 8 Carboplatin AUC 4 d1 Panitumumab 9 mg/kg/KG d1 q3w until progressive disease or for a max. of 6 cycles
The backbone chemotherapy (Caelyx or Gemcitabine-based) is specified by the investigator before randomization of a patient.
干预措施: pegylated liposomal doxorubicin (PLD) (Drug)
Experimental arm (A):
Caelyx 30 mg/m² d1 Carboplatin AUC 5 d1 Panitumumab 6 mg/kg/KG d1 + 15 q4w until progressive disease or for a max. of 6 cycles
OR
Gemcitabine 1000 mg/m² d1 + 8 Carboplatin AUC 4 d1 Panitumumab 9 mg/kg/KG d1 q3w until progressive disease or for a max. of 6 cycles
The backbone chemotherapy (Caelyx or Gemcitabine-based) is specified by the investigator before randomization of a patient.
干预措施: Carboplatin (Drug)
Experimental arm (A):
Caelyx 30 mg/m² d1 Carboplatin AUC 5 d1 Panitumumab 6 mg/kg/KG d1 + 15 q4w until progressive disease or for a max. of 6 cycles
OR
Gemcitabine 1000 mg/m² d1 + 8 Carboplatin AUC 4 d1 Panitumumab 9 mg/kg/KG d1 q3w until progressive disease or for a max. of 6 cycles
The backbone chemotherapy (Caelyx or Gemcitabine-based) is specified by the investigator before randomization of a patient.
干预措施: Gemcitabine (Drug)
Standard arm (B):
Caelyx 30 mg/m² d1 Carboplatin AUC 5 d1 q4w until progressive disease or for a max. of 6 cycles
OR
Gemcitabine 1000 mg/m² d1 + 8 Carboplatin AUC 4 d1 q3w until progressive disease or for a max. of 6 cycles
The backbone chemotherapy (Caelyx or Gemcitabine-based) is specified by the investigator before randomization of a patient.
干预措施: pegylated liposomal doxorubicin (PLD) (Drug)
Standard arm (B):
Caelyx 30 mg/m² d1 Carboplatin AUC 5 d1 q4w until progressive disease or for a max. of 6 cycles
OR
Gemcitabine 1000 mg/m² d1 + 8 Carboplatin AUC 4 d1 q3w until progressive disease or for a max. of 6 cycles
The backbone chemotherapy (Caelyx or Gemcitabine-based) is specified by the investigator before randomization of a patient.
干预措施: Carboplatin (Drug)
Standard arm (B):
Caelyx 30 mg/m² d1 Carboplatin AUC 5 d1 q4w until progressive disease or for a max. of 6 cycles
OR
Gemcitabine 1000 mg/m² d1 + 8 Carboplatin AUC 4 d1 q3w until progressive disease or for a max. of 6 cycles
The backbone chemotherapy (Caelyx or Gemcitabine-based) is specified by the investigator before randomization of a patient.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Progression-free survival (PFS) rate after 12 months.
时间窗: 12 month
PFS is defined as the time from randomisation to the time of disease progression or relapse (according to RECIST, not CA-125 only!) or death, or to the date of last tumor assessment without any such event (censored observation).
次要结局
- Duration of Tumor-Response(Duration of Therapy (Therapy is planned for 6 cycles of 3 resp. 4 weeks each, shorter or longer durations are possible))
- Progression-free survival(End of Follow-up (up to 1 year))
- Overall survival(End of Follow-up (up to 1 year))
- Maximum toxicity resp. AE grade per patient per toxicity resp. AE during therapy(Duration of Therapy (Therapy is planned for 6 cycles of 3 resp. 4 weeks each, shorter or longer durations are possible))
- Tumor Response Rate(Duration of Therapy (Therapy is planned for 6 cycles of 3 resp. 4 weeks each, shorter or longer durations are possible))