A Prospective Randomized Phase III Trial of Maintenance Pemetrexed Versus Observation in Patients With Recurrent or Metastatic Urothelial Carcinoma Who Completed First Line Platinum-based Chemotherapy Without Disease Progression
试验速览
- 阶段
- 3 期
- 入组人数
- 74
- 试验地点
- 21
- 主要终点
- progression free survival
研究概览
简要总结
This study aims to verify superiority of pemetrexed maintenance to observation for patient without disease progression after 1 st line cisplatin-based chemotherapy.
详细描述
Patients with unresectable locally advanced, recurrent, or metastatic urothelial carcinoma of bladder, ureter, or renal pelvis who do not experience disease progression after 4 to 6 cycles of 1 st line chemotherapy administration.
After completion of 4-6 cycles, patients without disease progression on CT which is taken within 3 weeks after administration of the last chemotherapy will be randomized within 4 weeks after administration of the last chemotherapy to assign either maintenance group or observation group.
Pemetrexed 500 mg/m 2 mixed in normal saline 100 mL as a 10 minute IV infusion on day 1 of each 21 day cycle, with vitamin supplementation (folic acid 1000μg daily orally from 7 days prior to treatment initiation and vitamin B12 1000 μg IM 7 days prior to treatment initiation and then every 3 cycles). Thereafter, vitamin B12 can be injected on the same day of pemetrexed infusion. Dexamethasone 4 mg orally twice daily for 3 days beginning the day before treatment to minimize cutaneous reactions.
Treatment continues until occurrence of disease progression or intolerable toxicities upto maximum of 16 cycles.
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
盲法说明
open label
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmation urothelial cancer of bladder, ureter, or renal pelvis.
- •Patients must present with locally advanced, recurrent or metastatic disease not amenable to surgery, radiotherapy, or combined modality therapy with curative intent.
- •Patients who were administered 4-6 cycles of cisplatin-based first line chemotherapy [GP (gemcitabine/cisplatin), classic MVAC (methotrexate/vinblastine/doxorubicin/cisplatin), or dose-dense MVAC] and were planned to undergo regular surveillance
- •ce after confirmation of absence of disease progression on CT taken within 3 week after the administration of the last cycle of 1st line chemotherapy.
- •For patients with recurrent disease who received prior adjuvant or neoadjuvant chemotherapy with cisplatin-containing regimen, the last administration of previous treatment should be administered at least 6 months before start date of 1st line chemotherapy.
- •Measurable disease according RECIST criteria v 1.
- •Age 20 years or older
- •ECOG performance status 2 or better
- •Adequate bone marrow, hepatic, and renal function
- •Signed and dated informed consent of document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment
排除标准
- •Prior systemic chemotherapy or immunotherapy for palliative aim before or after 1st line cisplatin-based chemotherapy. However, prior intravesical chemotherapy or immunotherapy is allowed.
- •Disease progression during or after 1st line cisplatin-based chemotherapy
- •Known CNS metastasis
- •Diagnosis of any serious secondary malignancy within the last 2 years, except for adequately treated basal cell or squamous cell carcinoma of skin, early gastric carcinoma, early stage thyroid carcinoma, insignificant prostate carcinoma, or in situ carcinoma of cervix uteri
- •Pregnancy or breast feeding.
- •Serious hypersensitivity reaction to pemetrexed.
- •Severe renal function impairment with creatinine clearance <45 mL/min by standard Cockcroft-Gault formula or GFR measured by Tc99m-DPTA serum clearance method.
- •Other severe acute or chronic medical or psychiatric condition
研究组 & 干预措施
pemetrexed maintenance
Drug: Pemetrexed Maintenance therapy: 500 mg/m^2, IV, on Day 1 of each 21-day cycle until progressive disease or treatment discontinuation.
Drug: folic acid 1000 μg daily orally from 7 days prior to treatment initiation until the end of treatment
Drug: vitamin B12 injection 1000 μg IM 7 days prior to treatment initiation and the every then every 3 cycles until the end of treatment
Drug: dexamethasone 4 mg twice orally for 3 days beginning the day before treatment until the end of treatment
干预措施: pemetrexed (Drug)
pemetrexed maintenance
Drug: Pemetrexed Maintenance therapy: 500 mg/m^2, IV, on Day 1 of each 21-day cycle until progressive disease or treatment discontinuation.
Drug: folic acid 1000 μg daily orally from 7 days prior to treatment initiation until the end of treatment
Drug: vitamin B12 injection 1000 μg IM 7 days prior to treatment initiation and the every then every 3 cycles until the end of treatment
Drug: dexamethasone 4 mg twice orally for 3 days beginning the day before treatment until the end of treatment
干预措施: Folic Acid (Drug)
pemetrexed maintenance
Drug: Pemetrexed Maintenance therapy: 500 mg/m^2, IV, on Day 1 of each 21-day cycle until progressive disease or treatment discontinuation.
Drug: folic acid 1000 μg daily orally from 7 days prior to treatment initiation until the end of treatment
Drug: vitamin B12 injection 1000 μg IM 7 days prior to treatment initiation and the every then every 3 cycles until the end of treatment
Drug: dexamethasone 4 mg twice orally for 3 days beginning the day before treatment until the end of treatment
干预措施: Vitamin B12 Injection (Drug)
pemetrexed maintenance
Drug: Pemetrexed Maintenance therapy: 500 mg/m^2, IV, on Day 1 of each 21-day cycle until progressive disease or treatment discontinuation.
Drug: folic acid 1000 μg daily orally from 7 days prior to treatment initiation until the end of treatment
Drug: vitamin B12 injection 1000 μg IM 7 days prior to treatment initiation and the every then every 3 cycles until the end of treatment
Drug: dexamethasone 4 mg twice orally for 3 days beginning the day before treatment until the end of treatment
干预措施: Dexamethasone (Drug)
结局指标
主要结局
progression free survival
时间窗: Every 9 weeks, from date of randomization until the date of first documented progression upto 24 months
Time between randomization and disease progression or death from any causes, whichever came first. Alive patients free of progression will be censored at the last follow-up
次要结局
- objective response rate(every 9 weeks, assess the best overall response from date of randomization until the date of first documented progression upto 24 months)
- Incidence of treatment-emergent adverse events(every 3 weeks for pemetrexed group, every 9 weeks for observation group from date of randomization until the date of first documented progression upto 24 months)
- overall survival(From date of randomization until the date of death from any cause, assessed up to 1 year after the end of treatment)
- Quality of Life(before randomization, then 9, 18, and 27 weeks after randomization)
研究者
JLee
Associated Professor
Asan Medical Center