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

Sponsor

Asan Medical Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT03193788

Collaborator

Korean Cancer Study Group (Other)

Enrollment

Locations

Arms

Anticipated Duration (Months)

3.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer Ureter Cancer Transitional Cell Carcinoma	Drug: pemetrexed Drug: Folic Acid Drug: Vitamin B12 Injection Drug: Dexamethasone	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

74 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Masking Description:

open label

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 1, 2017

Anticipated Primary Completion Date :

Dec 1, 2019

Anticipated Study Completion Date :

Jun 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	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 Other Names: Alimta Drug: Folic Acid folic acid 1000 μg daily orally from 7 days prior to treatment initiation until the end of treatment Other Names: Folvite FA-8 FaLessa Drug: Vitamin B12 Injection vitamin B12 1000 μg IM 7 days prior to treatment initiation and the end of treatment Other Names: Vitabee 12 Drug: Dexamethasone Dexamethasone 4 mg twice orally for 3 days beginning the day before treatment until the end of treatment to minimize cutaneous reactions Other Names: decadron
No Intervention: observation observation group will be observed with best supportive care until progressive disease

Arm

Intervention/Treatment

Experimental: 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

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

Other Names:

Alimta

Drug: Folic Acid

folic acid 1000 μg daily orally from 7 days prior to treatment initiation until the end of treatment

Other Names:

Folvite

FA-8

FaLessa

Drug: Vitamin B12 Injection

vitamin B12 1000 μg IM 7 days prior to treatment initiation and the end of treatment

Other Names:

Vitabee 12

Drug: Dexamethasone

Dexamethasone 4 mg twice orally for 3 days beginning the day before treatment until the end of treatment to minimize cutaneous reactions

Other Names:

decadron

No Intervention: observation

observation group will be observed with best supportive care until progressive disease

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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
Quality of Life [before randomization, then 9, 18, and 27 weeks after randomization]
QoL will be assessed by EORTC QLQ-C30 core questionaire

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hallym University Medical Center, Hallym University College of Medicine	Anyang	Korea, Republic of
2	Keimyeong University Dongsan Medical Center	Daegu	Korea, Republic of	700-712
3	Fatima Hospital	Daegu	Korea, Republic of
4	Chungnam University Hospital	Daejeon	Korea, Republic of	301-721
5	National Health Insurance Service Ilsan Hospital	Goyang	Korea, Republic of
6	Hallym University Dongtan Sacred Heart Hospital	Hwaseong-si	Korea, Republic of
7	Gil Medical Center	Incheon	Korea, Republic of	21565
8	Dong-A University Medical Center	Pusan	Korea, Republic of
9	Inje University Haeundae Paik Hospital	Pusan	Korea, Republic of
10	Pusan National University Hospital, Pusan National University School of Medicine	Pusan	Korea, Republic of
11	Asan Medical Center	Seoul	Korea, Republic of	138-736
12	Chung Ang University Hospital	Seoul	Korea, Republic of	156-755
13	Inje University Sanggye Paik Hospital	Seoul	Korea, Republic of
14	Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine	Seoul	Korea, Republic of
15	Korea University Anam Hospital	Seoul	Korea, Republic of
16	Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine	Seoul	Korea, Republic of
17	Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea	Seoul	Korea, Republic of
18	Yonsei Cancer Center	Seoul	Korea, Republic of
19	St. Vincent's Hospital, The Catholic University of Korea	Suwon	Korea, Republic of
20	Uijeongbu St Mary's hospital, Catholic university of Korea	Uijeongbu	Korea, Republic of
21	Pusan National University Yangsan Hospital	Yangsan	Korea, Republic of