Pemetrexed Maintenance in Patients With Urothelial Carcinoma Who Completed First Line Platinum-based Chemotherapy
PREMIER
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
1 other identifier
interventional
74
1 country
21
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Jan 2017
Typical duration for phase_3
21 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 13, 2016
CompletedStudy Start
First participant enrolled
January 1, 2017
CompletedFirst Posted
Study publicly available on registry
June 21, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2020
CompletedJune 21, 2017
May 1, 2017
2.9 years
August 13, 2016
June 18, 2017
Conditions
Outcome Measures
Primary Outcomes (1)
progression free survival
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
Every 9 weeks, from date of randomization until the date of first documented progression upto 24 months
Secondary Outcomes (4)
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
Study Arms (2)
pemetrexed maintenance
EXPERIMENTALDrug: 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
observation
NO INTERVENTIONobservation group will be observed with best supportive care until progressive disease
Interventions
Pemetrexed 500 mg/m2mixed in normal saline 100 mL as a 10 minute IV infusion on day 1 of each 21 day cycle
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
Dexamethasone 4 mg twice orally for 3 days beginning the day before treatment until the end of treatment to minimize cutaneous reactions
Eligibility Criteria
You may qualify if:
- 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 1.1.
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Asan Medical Centerlead
- Korean Cancer Study Groupcollaborator
Study Sites (21)
Hallym University Medical Center, Hallym University College of Medicine
Anyang, South Korea
Keimyeong University Dongsan Medical Center
Daegu, 700-712, South Korea
Fatima Hospital
Daegu, South Korea
Chungnam University Hospital
Daejeon, 301-721, South Korea
National Health Insurance Service Ilsan Hospital
Goyang, South Korea
Hallym University Dongtan Sacred Heart Hospital
Hwaseong-si, South Korea
Gil Medical Center
Incheon, 21565, South Korea
Dong-A University Medical Center
Pusan, South Korea
Inje University Haeundae Paik Hospital
Pusan, South Korea
Pusan National University Hospital, Pusan National University School of Medicine
Pusan, South Korea
Asan Medical Center
Seoul, 138-736, South Korea
Chung Ang University Hospital
Seoul, 156-755, South Korea
Inje University Sanggye Paik Hospital
Seoul, South Korea
Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
Seoul, South Korea
Korea University Anam Hospital
Seoul, South Korea
Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine
Seoul, South Korea
Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea
Seoul, South Korea
Yonsei Cancer Center
Seoul, South Korea
St. Vincent's Hospital, The Catholic University of Korea
Suwon, South Korea
Uijeongbu St Mary's hospital, Catholic university of Korea
Uijeongbu-si, South Korea
Pusan National University Yangsan Hospital
Yangsan, South Korea
Related Publications (6)
von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM, Kerbrat P, Sanchez Rovira P, Wersall P, Cleall SP, Roychowdhury DF, Tomlin I, Visseren-Grul CM, Conte PF. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000 Sep;18(17):3068-77. doi: 10.1200/JCO.2000.18.17.3068.
PMID: 11001674RESULTPaz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. PARAMOUNT: Final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013 Aug 10;31(23):2895-902. doi: 10.1200/JCO.2012.47.1102. Epub 2013 Jul 8.
PMID: 23835707RESULTBellmunt J, Theodore C, Demkov T, Komyakov B, Sengelov L, Daugaard G, Caty A, Carles J, Jagiello-Gruszfeld A, Karyakin O, Delgado FM, Hurteloup P, Winquist E, Morsli N, Salhi Y, Culine S, von der Maase H. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol. 2009 Sep 20;27(27):4454-61. doi: 10.1200/JCO.2008.20.5534. Epub 2009 Aug 17.
PMID: 19687335RESULTVaughn DJ, Broome CM, Hussain M, Gutheil JC, Markowitz AB. Phase II trial of weekly paclitaxel in patients with previously treated advanced urothelial cancer. J Clin Oncol. 2002 Feb 15;20(4):937-40. doi: 10.1200/JCO.2002.20.4.937.
PMID: 11844814RESULTSweeney CJ, Roth BJ, Kabbinavar FF, Vaughn DJ, Arning M, Curiel RE, Obasaju CK, Wang Y, Nicol SJ, Kaufman DS. Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium. J Clin Oncol. 2006 Jul 20;24(21):3451-7. doi: 10.1200/JCO.2005.03.6699.
PMID: 16849761RESULTGalsky MD, Moshier E, Krege S, Lin CC, Hahn N, Ecke T, Sonpavde G, Pond G, Godbold J, Oh WK, Bamias A. Posttreatment prognostic nomogram for patients with metastatic urothelial cancer completing first-line cisplatin-based chemotherapy. Urol Oncol. 2014 Jan;32(1):48.e1-8. doi: 10.1016/j.urolonc.2013.07.001. Epub 2013 Sep 18.
PMID: 24055428RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jae-Lyun Lee, MD, PhD
Asan Medical Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- open label
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associated Professor
Study Record Dates
First Submitted
August 13, 2016
First Posted
June 21, 2017
Study Start
January 1, 2017
Primary Completion
December 1, 2019
Study Completion
June 1, 2020
Last Updated
June 21, 2017
Record last verified: 2017-05