Pemetrexed Maintenance in Patients With Urothelial Carcinoma Who Completed First Line Platinum-based Chemotherapy

Bladder Cancer Clinical Trial

— PREMIER  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03193788
• Other study ID #: KCSG GU16-05
• Status: Recruiting
• Phase: Phase 3
• First received: August 13, 2016
• Last updated: June 18, 2017
• Start date: January 2017
• Est. completion date: June 2020

Study information

• Verified date: May 2017
• Source: Asan Medical Center
• Contact: Jae-Lyun Lee, MD, PhD
• Phone: 82 2 3010 5977
• Email: jaelyun[@]amc.seoul.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to verify superiority of pemetrexed maintenance to observation for patient without disease progression after 1 st line cisplatin-based chemotherapy.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 74
• Est. completion date: June 2020
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma
• Carcinoma, Transitional Cell
• Transitional Cell Carcinoma
• Ureter Cancer
• Ureteral Neoplasms
• Urinary Bladder Neoplasms

Intervention

Drug:
• pemetrexed
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
folic acid 1000 µg daily orally from 7 days prior to treatment initiation until the end of treatment
• Vitamin B12 Injection
vitamin B12 1000 µg IM 7 days prior to treatment initiation and the end of treatment
• Dexamethasone
Dexamethasone 4 mg twice orally for 3 days beginning the day before treatment until the end of treatment to minimize cutaneous reactions

Locations

Country	Name	City	State
Korea, Republic of	Hallym University Medical Center, Hallym University College of Medicine	Anyang
Korea, Republic of	Fatima Hospital	Daegu
Korea, Republic of	Keimyeong University Dongsan Medical Center	Daegu
Korea, Republic of	Chungnam University Hospital	Daejeon
Korea, Republic of	National Health Insurance Service Ilsan Hospital	Goyang
Korea, Republic of	Hallym University Dongtan Sacred Heart Hospital	Hwaseong-si
Korea, Republic of	Gil Medical Center	Incheon
Korea, Republic of	Dong-A University Medical Center	Pusan
Korea, Republic of	Inje University Haeundae Paik Hospital	Pusan
Korea, Republic of	Pusan National University Hospital, Pusan National University School of Medicine	Pusan
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Chung Ang University Hospital	Seoul
Korea, Republic of	Inje University Sanggye Paik Hospital	Seoul
Korea, Republic of	Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine	Seoul
Korea, Republic of	Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea	Seoul
Korea, Republic of	Yonsei Cancer Center	Seoul
Korea, Republic of	St. Vincent's Hospital, The Catholic University of Korea	Suwon
Korea, Republic of	Uijeongbu St Mary's hospital, Catholic university of Korea	Uijeongbu
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan

Sponsors (2)

Lead Sponsor	Collaborator
Asan Medical Center	Korean Cancer Study Group

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (6)

Bellmunt J, Théodore 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 — View 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 Ja — View 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 o — View 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. — View 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. — View 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 m — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	objective response rate	Objective response rate will be measured according to RECIST 1.1	every 9 weeks, assess the best overall response from date of randomization until the date of first documented progression upto 24 months
Secondary	Incidence of treatment-emergent adverse events	Safety assessed per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03	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
Secondary	overall survival	Time interval between randomization and death (all causes). Alive patients will be censored at the last date of news or data cut off	From date of randomization until the date of death from any cause, assessed up to 1 year after the end of treatment
Secondary	Quality of Life	QoL will be assessed by EORTC QLQ-C30 core questionaire	before randomization, then 9, 18, and 27 weeks after randomization