Clinical trial NCT03193788: Pemetrexed Maintenance in Patients With Urothelial Carcinoma Who Completed First Line Platinum-based Chemotherapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Bladder Cancer
Ureter Cancer
Transitional Cell Carcinoma
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Korean Cancer Study Group
First posted: 2017-06-21
Enrollment: 74
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: progression free survival
timeFrame: Every 9 weeks, from date of randomization until the date of first documented progression upto 24 months
Secondary outcomes:
measure: objective response rate
timeFrame: every 9 weeks, assess the best overall response from date of randomization until the date of first documented progression upto 24 months
measure: Incidence of treatment-emergent adverse events
timeFrame: 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
measure: overall survival
timeFrame: From date of randomization until the date of death from any cause, assessed up to 1 year after the end of treatment
measure: Quality of Life
timeFrame: before randomization, then 9, 18, and 27 weeks after randomization
Other outcomes:
Locations:
city: Anyang
country: Korea, Republic of
facility: Hallym University Medical Center, Hallym University College of Medicine
city: Daegu
country: Korea, Republic of
facility: Keimyeong University Dongsan Medical Center
city: Daegu
country: Korea, Republic of
facility: Fatima Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam University Hospital
city: Goyang
country: Korea, Republic of
facility: National Health Insurance Service Ilsan Hospital
city: Hwaseong-si
country: Korea, Republic of
facility: Hallym University Dongtan Sacred Heart Hospital
city: Incheon
country: Korea, Republic of
facility: Gil Medical Center
city: Pusan
country: Korea, Republic of
facility: Dong-A University Medical Center
city: Pusan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Pusan
country: Korea, Republic of
facility: Pusan National University Hospital, Pusan National University School of Medicine
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Chung Ang University Hospital
city: Seoul
country: Korea, Republic of
facility: Inje University Sanggye Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea
city: Seoul
country: Korea, Republic of
facility: Yonsei Cancer Center
city: Suwon
country: Korea, Republic of
facility: St. Vincent's Hospital, The Catholic University of Korea
city: Uijeongbu
country: Korea, Republic of
facility: Uijeongbu St Mary's hospital, Catholic university of Korea
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
Study officials:
affiliation: Asan Medical Center
name: Jae-Lyun Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Paz-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.
citation: Bellmunt 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.
citation: Vaughn 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.
citation: Sweeney 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.
citation: Galsky 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.