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

June 18, 2017 updated by: JLee, Asan Medical Center

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

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

74

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Korea, Republic of
      • Anyang, Korea, Republic of
        • Recruiting
        • Hallym University Medical Center, Hallym University College of Medicine
        • Contact:
      • Daegu, Korea, Republic of
      • Daegu, Korea, Republic of, 700-712
        • Recruiting
        • Keimyeong University Dongsan Medical Center
      • Daejeon, Korea, Republic of, 301-721
        • Recruiting
        • Chungnam University Hospital
        • Contact:
      • Goyang, Korea, Republic of
        • Recruiting
        • National Health Insurance Service Ilsan Hospital
        • Contact:
      • Hwaseong-si, Korea, Republic of
      • Incheon, Korea, Republic of, 21565
      • Pusan, Korea, Republic of
        • Recruiting
        • Inje University Haeundae Paik Hospital
        • Contact:
      • Pusan, Korea, Republic of
        • Recruiting
        • Pusan National University Hospital, Pusan National University School of Medicine
        • Contact:
      • Pusan, Korea, Republic of
        • Recruiting
        • Dong-A University Medical Center
        • Contact:
          • Suee Lee
      • Seoul, Korea, Republic of, 138-736
        • Recruiting
        • Asan Medical Center
      • Seoul, Korea, Republic of
      • Seoul, Korea, Republic of
        • Recruiting
        • Inje University Sanggye Paik Hospital
        • Contact:
      • Seoul, Korea, Republic of
        • Recruiting
        • Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
        • Contact:
      • Seoul, Korea, Republic of
        • Recruiting
        • Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine
        • Contact:
          • Bhum Suk Keam
      • Seoul, Korea, Republic of
        • Recruiting
        • Yonsei Cancer Center
        • Contact:
      • Seoul, Korea, Republic of, 156-755
      • Seoul, Korea, Republic of
        • Recruiting
        • Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea
        • Contact:
      • Suwon, Korea, Republic of
        • Recruiting
        • St. Vincent's Hospital, The Catholic University of Korea
      • Uijeongbu, Korea, Republic of
        • Recruiting
        • Uijeongbu St Mary's hospital, Catholic university of Korea
        • Contact:
      • Yangsan, Korea, Republic of
        • Recruiting
        • Pusan National University Yangsan Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
progression free survival
Time Frame: 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
Every 9 weeks, from date of randomization until the date of first documented progression upto 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
objective response rate
Time Frame: 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
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
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
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
overall survival
Time Frame: 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
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
Time Frame: before randomization, then 9, 18, and 27 weeks after randomization
QoL will be assessed by EORTC QLQ-C30 core questionaire
before randomization, then 9, 18, and 27 weeks after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Asan Medical Center

Collaborators

Korean Cancer Study Group

Investigators

  • Principal Investigator: Jae-Lyun Lee, MD, PhD, Asan Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2017

Primary Completion (Anticipated)

December 1, 2019

Study Completion (Anticipated)

June 1, 2020

Study Registration Dates

First Submitted

August 13, 2016

First Submitted That Met QC Criteria

June 18, 2017

First Posted (Actual)

June 21, 2017

Study Record Updates

Last Update Posted (Actual)

June 21, 2017

Last Update Submitted That Met QC Criteria

June 18, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KCSG GU16-05

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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