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

Primary Purpose

Bladder Cancer, Ureter Cancer, Transitional Cell Carcinoma

Status
Unknown status
Phase
Phase 3
Locations
Korea, Republic of
Study Type
Interventional
Intervention
pemetrexed
Folic Acid
Vitamin B12 Injection
Dexamethasone
Sponsored by
Asan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Cancer

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hallym University Medical Center, Hallym University College of MedicineRecruiting
  • Keimyeong University Dongsan Medical CenterRecruiting
  • Fatima HospitalRecruiting
  • Chungnam University HospitalRecruiting
  • National Health Insurance Service Ilsan HospitalRecruiting
  • Hallym University Dongtan Sacred Heart HospitalRecruiting
  • Gil Medical CenterRecruiting
  • Dong-A University Medical CenterRecruiting
  • Inje University Haeundae Paik HospitalRecruiting
  • Pusan National University Hospital, Pusan National University School of MedicineRecruiting
  • Asan Medical CenterRecruiting
  • Chung Ang University HospitalRecruiting
  • Inje University Sanggye Paik HospitalRecruiting
  • Kangbuk Samsung Hospital, Sungkyunkwan University School of MedicineRecruiting
  • Korea University Anam HospitalRecruiting
  • Seoul National University Hospital, Cancer Research Institute, Seoul National University College of MedicineRecruiting
  • Seoul St. Mary's Hospital, College of Medicine, The Catholic University of KoreaRecruiting
  • Yonsei Cancer CenterRecruiting
  • St. Vincent's Hospital, The Catholic University of KoreaRecruiting
  • Uijeongbu St Mary's hospital, Catholic university of KoreaRecruiting
  • Pusan National University Yangsan HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

pemetrexed maintenance

observation

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

objective response rate
Objective response rate will be measured according to RECIST 1.1
Incidence of treatment-emergent adverse events
Safety assessed per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03
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
Quality of Life
QoL will be assessed by EORTC QLQ-C30 core questionaire

Full Information

First Posted
August 13, 2016
Last Updated
June 18, 2017
Sponsor
Asan Medical Center
Collaborators
Korean Cancer Study Group
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1. Study Identification

Unique Protocol Identification Number
NCT03193788
Brief Title
Pemetrexed Maintenance in Patients With Urothelial Carcinoma Who Completed First Line Platinum-based Chemotherapy
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Unknown status
Study Start Date
January 2017 (Actual)
Primary Completion Date
December 2019 (Anticipated)
Study Completion Date
June 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Asan Medical Center
Collaborators
Korean Cancer Study Group

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer, Ureter Cancer, Transitional Cell Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
open label
Allocation
Randomized
Enrollment
74 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
pemetrexed maintenance
Arm Type
Experimental
Arm Description
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
Arm Title
observation
Arm Type
No Intervention
Arm Description
observation group will be observed with best supportive care until progressive disease
Intervention Type
Drug
Intervention Name(s)
pemetrexed
Other Intervention Name(s)
Alimta
Intervention Description
Pemetrexed 500 mg/m2mixed in normal saline 100 mL as a 10 minute IV infusion on day 1 of each 21 day cycle
Intervention Type
Drug
Intervention Name(s)
Folic Acid
Other Intervention Name(s)
Folvite, FA-8, FaLessa
Intervention Description
folic acid 1000 μg daily orally from 7 days prior to treatment initiation until the end of treatment
Intervention Type
Drug
Intervention Name(s)
Vitamin B12 Injection
Other Intervention Name(s)
Vitabee 12
Intervention Description
vitamin B12 1000 μg IM 7 days prior to treatment initiation and the end of treatment
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
decadron
Intervention Description
Dexamethasone 4 mg twice orally for 3 days beginning the day before treatment until the end of treatment to minimize cutaneous reactions
Primary Outcome Measure Information:
Title
progression free survival
Description
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
Time Frame
Every 9 weeks, from date of randomization until the date of first documented progression upto 24 months
Secondary Outcome Measure Information:
Title
objective response rate
Description
Objective response rate will be measured according to RECIST 1.1
Time Frame
every 9 weeks, assess the best overall response from date of randomization until the date of first documented progression upto 24 months
Title
Incidence of treatment-emergent adverse events
Description
Safety assessed per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03
Time Frame
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
Title
overall survival
Description
Time interval between randomization and death (all causes). Alive patients will be censored at the last date of news or data cut off
Time Frame
From date of randomization until the date of death from any cause, assessed up to 1 year after the end of treatment
Title
Quality of Life
Description
QoL will be assessed by EORTC QLQ-C30 core questionaire
Time Frame
before randomization, then 9, 18, and 27 weeks after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jae-Lyun Lee, MD, PhD
Phone
82 2 3010 5977
Email
jaelyun@amc.seoul.kr
First Name & Middle Initial & Last Name or Official Title & Degree
MiRan Kim
Phone
82 2 3010 5576
Email
crnonc12@amc.seoul.kr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jae-Lyun Lee, MD, PhD
Organizational Affiliation
Asan Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hallym University Medical Center, Hallym University College of Medicine
City
Anyang
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ho Young Kim
Email
ksfam@daum.net
Facility Name
Keimyeong University Dongsan Medical Center
City
Daegu
ZIP/Postal Code
700-712
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jin Young Kim, MD
Email
takgu@dsmc.or.kr
Facility Name
Fatima Hospital
City
Daegu
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jung Lim Lee
Email
junglim3@gmail.com
Facility Name
Chungnam University Hospital
City
Daejeon
ZIP/Postal Code
301-721
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hyo Jin Lee, MD, PhD.
Email
cymed@cnu.ac.kr
Facility Name
National Health Insurance Service Ilsan Hospital
City
Goyang
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Soo Jung Hong
Email
suzzy901@nhimc.or.kr
Facility Name
Hallym University Dongtan Sacred Heart Hospital
City
Hwaseong-si
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hyun Ae Jung
Email
hyunaejung@hallym.or.kr
Facility Name
Gil Medical Center
City
Incheon
ZIP/Postal Code
21565
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Inkeun Park, MD
Email
ingni79@hanmail.net
Facility Name
Dong-A University Medical Center
City
Pusan
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Suee Lee
Facility Name
Inje University Haeundae Paik Hospital
City
Pusan
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Il-Hwan Kim
Email
onelement@daum.net
Facility Name
Pusan National University Hospital, Pusan National University School of Medicine
City
Pusan
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hyo Jung Kim
Email
leonkim80@naver.com
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jae-Lyun Lee, MD, PhD
Phone
82 2 3010 5977
Email
jaelyun@amc.seoul.kr
Facility Name
Chung Ang University Hospital
City
Seoul
ZIP/Postal Code
156-755
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hee Joon Kim, MD
Email
heejun.dino11@gmail.com
Facility Name
Inje University Sanggye Paik Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Byeong Seok Sohn
Email
imbs@paik.ac.kr
Facility Name
Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yun-Gyoo Lee
Email
gosciny@gmail.com
Facility Name
Korea University Anam Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yoon Ji Choi
Email
yoonji23@hanmail.net
Facility Name
Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bhum Suk Keam
Email
bhumsuk@snu.ac.kr
Facility Name
Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
In-Ho Kim
Email
ihkmd@naver.com
Facility Name
Yonsei Cancer Center
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sang Joon Shin
Email
ssj338@yuhs.ac
Facility Name
St. Vincent's Hospital, The Catholic University of Korea
City
Suwon
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Byoung Yong Shim
Email
shimby@catholic.ac.kr
Facility Name
Uijeongbu St Mary's hospital, Catholic university of Korea
City
Uijeongbu
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yoon Ho Ko
Email
koyoonho@catholic.ac.kr
Facility Name
Pusan National University Yangsan Hospital
City
Yangsan
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kwonoh Park
Email
parkkoh@hanmail.net

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
11001674
Citation
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Results Reference
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Citation
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Results Reference
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Citation
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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.
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Pemetrexed Maintenance in Patients With Urothelial Carcinoma Who Completed First Line Platinum-based Chemotherapy

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