Bladder Cancer, Transitional Cell Carcinoma, Ureter Cancer
Conditions
Brief summary
This study aims to verify superiority of pemetrexed maintenance to observation for patient without disease progression after 1 st line cisplatin-based chemotherapy.
Detailed description
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.
Interventions
DRUGpemetrexed
Pemetrexed 500 mg/m2mixed in normal saline 100 mL as a 10 minute IV infusion on day 1 of each 21 day cycle
DRUGFolic Acid
folic acid 1000 μg daily orally from 7 days prior to treatment initiation until the end of treatment
vitamin B12 1000 μg IM 7 days prior to treatment initiation and the end of treatment
DRUGDexamethasone
Dexamethasone 4 mg twice orally for 3 days beginning the day before treatment until the end of treatment to minimize cutaneous reactions
Sponsors
Korean Cancer Study Group
Asan Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
open label
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmation urothelial cancer of bladder, ureter, or renal pelvis. 2. Patients must present with locally advanced, recurrent or metastatic disease not amenable to surgery, radiotherapy, or combined modality therapy with curative intent. 3. 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 4. 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. 5. 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. 6. Measurable disease according RECIST criteria v 1.1. 7. Age 20 years or older 8. ECOG performance status 2 or better 9. Adequate bone marrow, hepatic, and renal function 10. 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
Exclusion criteria
1. Prior systemic chemotherapy or immunotherapy for palliative aim before or after 1st line cisplatin-based chemotherapy. However, prior intravesical chemotherapy or immunotherapy is allowed. 2. Disease progression during or after 1st line cisplatin-based chemotherapy 3. Known CNS metastasis 4. 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 5. Pregnancy or breast feeding. 6. Serious hypersensitivity reaction to pemetrexed. 7. Severe renal function impairment with creatinine clearance \<45 mL/min by standard Cockcroft-Gault formula or GFR measured by Tc99m-DPTA serum clearance method. 8. Other severe acute or chronic medical or psychiatric condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| progression free survival | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life | before randomization, then 9, 18, and 27 weeks after randomization | QoL will be assessed by EORTC QLQ-C30 core questionaire |
| 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 | Objective response rate will be measured according to RECIST 1.1 |
| 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 | Safety assessed per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 |
| overall survival | From date of randomization until the date of death from any cause, assessed up to 1 year after the end of treatment | Time interval between randomization and death (all causes). Alive patients will be censored at the last date of news or data cut off |
Countries
South Korea
Contacts
Primary ContactJae-Lyun Lee, MD, PhD
Backup ContactMiRan Kim
Outcome results
None listed